Comparative Effectiveness of Manual Therapy, Exercise Therapy, and Combined Therapy for Chronic Low Back Pain: A Comprehensive Retrospective Cohort Study

Comparative Effectiveness of Manual Therapy, Exercise Therapy, and Combined Therapy for Chronic Low Back Pain: A Comprehensive Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparative Effectiveness of Manual Therapy, Exercise Therapy, and Combined Therapy for Chronic Low Back Pain: A Comprehensive Retrospective Cohort Study Yazeed Timraz, Ali Sahari, Faisal Alotaibi, Shouq Almutairi, Ahmed Hamami, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7720973/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The best conservative treatment for chronic low back pain (CLBP) remains uncertain. This study aimed to evaluate the effectiveness of manual therapy (MT), exercise therapy (ET), and their combination (MT + ET) in real-world clinical practice. Secondary outcomes and subgroup analyses were also included. Methods A retrospective cohort study was conducted on 302 patients with chronic low back pain (CLBP) treated at the Rehabilitation Department of the National Guard Hospital in Riyadh, Saudi Arabia, between 2023 and 2024. The patients were divided into three groups: manual therapy (MT), exercise therapy (ET), and a combination of both (MT + ET). The main outcomes were pain intensity, measured with the Visual Analog Scale (VAS), and functional disability, assessed with the Oswestry Disability Index (ODI). Secondary outcomes included medication use, recurrence of pain, and follow-up duration. Subgroup analyses examined treatment effects according to age, gender, baseline pain severity, and body mass index (BMI). Results All three groups showed significant improvement in both pain and disability (p < 0.001). The combined therapy group achieved the greatest reductions in pain (mean change − 5.0) and disability (mean change − 15.9), compared to ET (pain − 4.0, disability − 12.4) and MT (pain − 2.3, disability − 6.0) (p < 0.001 for all). The combined therapy group achieved clinically meaningful improvement in 78% of patients compared to 55.5% for exercise therapy and 0% for manual therapy. Combined therapy showed superior medication reduction (72.5% NSAIDs reduction vs 51.2% ET vs 45.5% MT) and lowest recurrence rates (4.7% vs 10.4% vs 18.2%). Patients with severe baseline pain showed significantly greater improvement than those with moderate pain (p = 0.008). BMI analysis revealed that overweight patients showed the greatest response to combined therapy (5.3 points pain reduction), while obese patients had significantly reduced functional improvement (p = 0.003). Conclusion The combination of manual therapy and exercise therapy is more effective than either treatment alone for reducing pain, improving function, lowering medication use, and preventing recurrence in patients with chronic low back pain. The findings also show that treatment outcomes vary according to baseline pain severity and body mass index (BMI). Overweight patients had the best response to combined therapy, which suggests that treatment should be adjusted based on patient characteristics. Trial Registration Not applicable. This study was not prospectively registered as a clinical trial. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Health sciences/Signs and symptoms Chronic low back pain Manual therapy Exercise therapy Combined therapy Retrospective cohort Pain management Functional disability Medication use Recurrence Body mass index Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1. Introduction Chronic low back pain (CLBP) is one of the main causes of disability in the world. In Saudi Arabia, it is very common, with rates between 53.2% and 79.17% in different groups [ 1 ]. The condition is a big problem for health systems because it lasts a long time and costs a lot. Although many studies have been done, the best way to treat it without surgery or medicine is still not clear. Exercise therapy (ET) and manual therapy (MT) are usually advised as the first treatments. However, it is still debated whether one is better than the other or if using both together works best. Research shows that both exercise therapy (ET) and manual therapy (MT) can help reduce pain and disability. However, when used alone, neither is always better than the other. Guidelines such as those from NICE [ 2 ] and the American College of Physicians [ 3 ] suggest that exercise should be the main part of treatment. Manual therapy is advised only when used together with exercise. This shows that single treatments give only small improvements, while combining methods may work better for the complex nature of CLBP. Because of these uncertainties, more research is needed to test how exercise therapy (ET) and manual therapy (MT) work alone and together. Most studies so far are randomized controlled trials with strict rules for who can take part, which makes it hard to apply the results to all patients. Real-world studies are needed to see how these treatments work in normal clinical practice. This study looks at the outcomes of ET, MT, and their combination in patients with chronic low back pain, focusing on pain, disability, recurrence, and medication use. The next section reviews the main studies on how these therapies compare. 2. Literature Review 2.1. Equivalence of Single Interventions Many studies show that exercise therapy (ET) and manual therapy (MT) give similar results when used alone for chronic low back pain (CLBP). A recent review and meta-analysis by González-Gómez and others [ 4 ], which included six trials with 743 patients, found no clear difference between ET and MT overall. However, ET showed a small long-term benefit for reducing disability (SMD − 0.25, 95% CI − 0.43 to − 0.07). The strength of this evidence was rated very low because of the small number of patients and differences between the studies. A Cochrane review by Hayden and others [ 5 ], which included 249 trials with 24,486 participants, found that exercise therapy (ET) works better than no treatment, usual care, or placebo. ET reduced pain (MD − 15.2/100) and improved function (MD − 6.8/100). However, when ET was directly compared with manual therapy (MT), there were no major differences in pain (MD 1.0, 95% CI − 3.1 to 5.1) or in functional outcomes. Evidence from Gomes-Neto and others [ 6 ] also shows that exercise and manual therapy (MT) give similar results. Stabilization exercises reduced pain and disability to the same level as MT, with no clear differences between the groups. However, stabilization exercises worked better than general exercise in some outcomes. Overall, the findings show that exercise therapy (ET) and manual therapy (MT) work equally well when used alone, with no strong evidence that one is better than the other. This means that the choice between them often depends on patient preference, the skills of the clinician, and what resources are available, rather than clear proof of one being more effective. Because of this, more studies are now looking at whether combining ET and MT can give better results. 2.2. Superiority of Combined Approaches Some studies show that combining manual therapy (MT) with exercise therapy (ET) may give better results for chronic low back pain (CLBP), but the evidence is not consistent. A recent review of 10 trials found that ET + MT improved pain and disability in the short term, but the studies were very different from each other and did not give strong long-term results [ 7 ]. Small trials also showed that ET + MT reduced pain and disability within six weeks [ 8 ]. Another larger trial did not find significant clinical differences between groups but showed that combined care might save costs [ 9 ]. Overall, ET + MT seems to give useful short-term benefits and may reduce costs, but the results are mixed. More large, high-quality studies are needed to know if the benefits last and if the combined approach is truly cost-effective. To understand this better, it is also important to look at the limits of using ET and MT alone. 2.3. Limitations of Isolated Interventions Although exercise therapy (ET) and manual therapy (MT) are helpful, using them alone has clear limits. A recent review on isolated lumbar extension (ILEX) training showed that it reduced pain (ES − 0.63, p = 0.004), but it did not improve disability or strength, with the certainty of this evidence rated very low [ 10 ]. In another study, Koumantakis and others [ 11 ] found that adding stabilization training to a general exercise program did not improve outcomes for people with recurrent low back pain. In fact, general exercise alone gave better short-term results for reducing disability. Overall, the evidence shows that exercise or manual therapy alone can give some benefits, but these are often small, uncertain, or do not last long. This supports the idea of using a combined approach, such as exercise therapy (ET) with manual therapy (MT), which may give stronger and longer-lasting results. The history of research on low back pain also shows that there are still many gaps in evidence, and these continue to make clinical practice difficult. 2.4. Historical Perspective and Evidence Gaps Early trials gave useful background for how conservative treatments developed for chronic low back pain (CLBP). The results were mixed. Some studies showed benefits for manual therapy, others supported combined care, while some found no clear differences [ 12 , 13 , 14 , 15 , 16 ]. Overall, these studies showed that outcomes varied, and pain relief did not always lead to long-term functional improvement. Recent studies have also shown mixed results. Extra methods, such as myofascial release and Mulligan mobilization, did not give clear extra benefits when added to spinal manipulation [ 17 , 18 , 19 ]. This suggests that adding more passive treatments does not always lead to better outcomes. Systematic Reviews have tried to bring this evidence together. Coulter and others [ 20 ] found moderate-quality evidence that spinal manipulation and mobilization can slightly reduce pain and improve function, but the results of the trials were too different to be fully certain. A Cochrane review by Rubinstein and others [ 21 ] also showed that spinal manipulation gave results similar to other recommended treatments such as exercise, with only small short-term benefits. Even with these reviews, many questions remain. Strategies that target subgroups have not given consistent benefits [ 22 ]. The best way to combine treatments, the right dosage, and how long the effects last are still unclear. From a cost view, Gedin and others [ 9 ] ran a trial comparing physiotherapy, chiropractic care, their combination, and advice, these are not the same as standard ET or MT, but the results suggested that the combined care might be more cost-effective. However, the trial was too small to be sure, so the results should be read with caution. In summary, single treatments give only small benefits. Combined approaches may help in the short term, but their long-term value for patients and costs is still not clear. This gap is more obvious in Saudi Arabia, where ET and MT are often used together, but there are limited local controlled trials [ 23 , 24 ]. This shows the need for large real-world studies that directly compare ET, MT, and their combination. These studies should look at important outcomes such as pain, disability, recurrence, and use of medicine. The current study was designed to fill this gap. 3. Methodology 3.1. Study Design This study used a retrospective cohort design to compare three treatments for chronic low back pain (CLBP): manual therapy (MT), exercise therapy (ET), and a combination of both (MT + ET). The patients were taken from those who received outpatient physiotherapy for non-specific CLBP at the Rehabilitation Department in National Guard Hospital between August 2023 and August 2024. This design was chosen to test how these treatments work in real clinical practice, using data collected from electronic health records (EHR). The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [ 25 ]. 3.2. Study Population The study included adult patients (18 years and older) who had non-specific chronic low back pain (CLBP) and started treatment at the outpatient physical therapy department during the study period. Inclusion criteria : Age 18 years or older. Diagnosis of non-specific CLBP, defined as pain lasting more than 3 months, based on the NIH Task Force recommendations [ 26 ]. Completion of at least four treatment sessions of MT, ET, or MT + ET. At least one pre-treatment and one post-treatment outcome recorded in the EHR. Exclusion criteria : Low back pain from specific causes such as fracture, tumor, infection, inflammatory conditions, radiculopathy, or spinal stenosis, as defined in the European guidelines [ 27 ]. Previous spinal surgery. Pregnancy. Any condition that the treating clinician judged as unsafe for the interventions. 3.3. Interventions Patients were placed into three groups based on the treatments recorded in the EHR: manual therapy (MT), exercise therapy (ET), or a combination of both (MT + ET). Manual Therapy (MT) : This group included patients who received treatments such as joint mobilization, manipulation, soft tissue massage, and myofascial release. These techniques are part of standard physiotherapy practice [ 28 ]. Exercise Therapy (ET) : This group included patients who followed exercise programs such as strengthening, stretching, motor control training, and aerobic exercises. These programs were based on evidence-based guidelines [ 3 , 29 ]. Combined Therapy (MT + ET) : This group included patients who received both manual therapy (MT) and exercise therapy (ET) during their treatment. The order or proportion of each treatment was not restricted. The groups were defined using the "TherapyType" variable in the EHR. Information about how the care was given, including the frequency, duration, and techniques used in each group, was also collected. 3.4. Outcome Measures 3.4.1. Primary Outcomes The main outcomes were pain and functional disability. These were measured at the start of treatment and after treatment. Pain Intensity : Measured with the Visual Analog Scale (VAS). A score of 0 means “no pain” and 10 means “worst pain.” The VAS is a reliable tool to measure pain [ 30 ]. Functional Disability : Measured with the Oswestry Disability Index (ODI). This 10-question tool measures how low back pain affects daily life. Scores range from 0 (no disability) to 100 (worst disability). The ODI is a standard and valid tool [ 31 ]. A change of at least 2 points (MCID) on the VAS and 10 points on the ODI was used to define meaningful improvement, based on published recommendations [ 32 ]. 3.4.2. Secondary Outcomes The secondary outcomes were: Medication use : Use of pain medicine before and after treatment. This included NSAIDs, opioids, acetaminophen, or combined drugs. If a combination was used (such as NSAIDs with muscle relaxants), it was counted under the main drug type. Pain recurrence : The number of patients who needed more treatment for low back pain during follow-up. Follow-up duration : The time in months from the end of treatment to the last visit recorded. Treatment adherence : The number of sessions completed compared with the number of sessions prescribed. 3.4.3. Pain Categorization Pain severity was grouped using VAS scores. A score of 1–4 meant mild pain, 5–6 meant moderate pain, and 7–10 meant severe pain. These cutoffs have been shown in many studies to work well for identifying how pain affects function [ 33 ]. The 11-point numeric rating scale is also a reliable and sensitive tool for measuring chronic pain [ 34 ]. 3.5. Data Extraction Data were taken from the EHR using a standard form to keep results consistent. The data included: Patient details : Age, gender, and BMI. Clinical details : How long symptoms lasted, history of low back pain, and baseline pain category. Treatment details : Treatment group (MT, ET, or MT + ET), number of sessions, and length of care. Outcomes : VAS and ODI scores before and after treatment, medication use, pain recurrence, and follow-up time. To make sure the data were reliable, all reviewers were trained in the same way. Reliability was tested on 10% of the sample. Agreement was very high for the main outcomes (VAS ICC = 0.94; ODI ICC = 0.91) and for other key data such as treatment type (κ = 0.89) and medication use (κ = 0.86). Any disagreements were discussed and solved with a third reviewer if needed. 3.6. Statistical Analysis All statistical analyses were performed using Python (version 3.11) with the pandas, numpy, scipy, and matplotlib libraries. A two-tailed significance level of p < 0.05 was used for all tests. Descriptive Analysis and Baseline Comparisons : Descriptive statistics (means, standard deviations, frequencies, and percentages) were used to summarize patient characteristics. To assess baseline comparability between the three treatment groups, one-way ANOVA was used for continuous variables (e.g., age, baseline VAS) and chi-square tests were used for categorical variables (e.g., gender). Primary and Secondary Outcome Analysis : The primary analysis was a complete case analysis. Change scores (post-treatment minus baseline) were calculated for VAS and ODI. A one-way ANOVA was used to compare the mean change scores between the three treatment groups. If the overall test was significant, pairwise comparisons were conducted using t-tests with appropriate correction for multiple comparisons. Cohen's d was calculated to determine the effect size of the differences. For secondary outcomes, chi-square tests were used for categorical variables (medication use, recurrence) and ANOVA for continuous variables (follow-up duration). Subgroup and Sensitivity Analyses : To explore potential effect modifiers, pre-planned subgroup analyses were conducted by stratifying patients by age, gender, baseline pain severity, and BMI. The robustness of the findings was assessed through sensitivity analyses, including multiple imputation for missing data (see Section 3.10 ). 3.7. Confounding and Statistical Adjustment To control for potential confounding and estimate adjusted treatment effects, multivariable linear regression models were developed for the primary outcomes (change in VAS and ODI scores). Potential confounders were identified a priori and included age, gender, BMI, and baseline VAS and ODI scores. In the models, the treatment group was the primary independent variable (with manual therapy as the reference group), and the aforementioned confounders were included as covariates. Both unadjusted and adjusted treatment effect estimates, along with their 95% confidence intervals, were calculated. Model assumptions were checked via residual analysis, and model fit was assessed using R-squared values. 3.8. Addressing Potential Sources of Bias Several steps were taken to reduce bias. To avoid selection bias, the inclusion and exclusion criteria were applied strictly to all patients in the study. Information bias was reduced by using a standard data collection process and by confirming high agreement between reviewers (see Section 3.5 ). Using structured EHR data helped prevent errors in classifying treatments. Outcomes were taken from recorded data instead of patients, which reduced recall bias. Missing data were checked using complete case analysis and tested further in sensitivity analyses. 3.9. Sample Size Calculation A sample size calculation was done before the study for the primary outcome (change in VAS scores). To find a medium effect size (f = 0.25) with 80% power and a significance level of 0.05 in a one-way ANOVA with three groups, at least 159 patients (53 in each group) were needed. The calculation was done using G*Power. The final study included 302 patients, which was more than the required number. A post-hoc analysis showed that the power was greater than 0.90 for finding the differences in VAS change scores. 3.10. Sensitivity Analysis To assess the robustness of the primary findings, three sensitivity analyses were planned: Multiple Imputation : To handle missing data, the main analysis was repeated using datasets created with multiple imputation by chained equations (MICE). Per-Protocol Analysis : This analysis included only patients who finished all treatment sessions to test the effect of treatment adherence. Alternative Model : The analysis was repeated with a different statistical model to check if the results stayed consistent. The results of these analyses were compared to the primary findings to evaluate the stability of the conclusions. 3.11. Ethical Considerations The study protocol was approved by the Institutional Review Board of King Abdullah International Medical Research Center (IRB #00000169625) and adhered to the principles of the Declaration of Helsinki. The IRB granted a waiver of informed consent due to the retrospective and use of de-identified nature of the data. To ensure confidentiality, all patient data were anonymized and stored on a secure server with access restricted to the research team. 4. Results 4.1. Participant Characteristics and Study Flow A total of 379 patients with chronic low back pain were found during the study period. After applying the eligibility criteria, 302 patients (79.7%) were included in the final analysis (Fig. 1 ). The main reasons for exclusion were specific spinal problems (n = 8), previous spinal surgery (n = 4), pregnancy (n = 2), missing therapy data (n = 33), and incomplete outcome measures (n = 30). The data were almost complete. Post-treatment pain scores (VAS) were available for 98.7% of patients, and disability scores (ODI) for 98.0%. The missing data were very small, random, and showed no clear differences between groups (Table S2, Supplementary). Baseline characteristics were also similar between the patients included and those excluded, showing that the final cohort was representative (Table S1 , Supplementary). Baseline demographic and clinical characteristics are shown in Table 1 . The three treatment groups were similar in age, sex, BMI, and symptom duration (all p > 0.05). Overall, patients had a mean age of 45.9 ± 12.9 years, were predominantly female (62%), and presented with severe baseline pain (mean VAS 7.4 ± 1.4) and substantial functional disability (mean ODI 66.0 ± 18.4). Table 1 Baseline Characteristics of Study Participants by Treatment Group Treatment Group N Age (years) Female, n (%) BMI (kg/m²) Pain Duration (weeks) Sessions Attended Baseline Pain VAS Baseline ODI Combined Therapy 127 44.9 ± 12.0 80 (63.0%) 27.8 ± 4.9 25.2 ± 4.4 17.0 ± 3.9 7.4 ± 1.5 64.6 ± 19.2 Exercise Therapy 164 46.6 ± 13.5 101 (61.6%) 28.0 ± 4.5 25.2 ± 4.1 12.2 ± 3.4 7.4 ± 1.3 66.2 ± 18.4 Manual Therapy 11 46.1 ± 14.3 5 (45.5%) 27.7 ± 6.2 26.3 ± 4.9 7.3 ± 2.7 7.8 ± 1.1 70.7 ± 15.4 Values are presented as mean ± standard deviation or n (%). VAS = Visual Analog Scale; ODI = Oswestry Disability Index. No significant differences between groups (p > 0.05 for all comparisons). 4.2. Primary Treatment Outcomes All three treatment groups showed significant improvement in pain (VAS) and disability (ODI) from before to after treatment (all p < 0.001). The greatest improvements were in the combined therapy group, followed by exercise therapy. Manual therapy showed the smallest improvements. On average, patients in the combined therapy group achieved a 5.0-point reduction in VAS and a 15.9-point reduction in ODI, compared with 4.0 and 12.4 points in the exercise therapy group and 2.3 and 6.0 points in the manual therapy group, respectively (Table 2 ; Figs. 2 – 3 ). Between-group comparisons confirmed that combined therapy was significantly more effective than both exercise therapy and manual therapy (p < 0.01 for all). Exercise therapy also outperformed manual therapy (p < 0.05). Table 2 Primary Treatment Outcomes by Group Treatment Group N Pain VAS Baseline Pain VAS Post-treatment Pain VAS Change ODI Baseline ODI Post-treatment ODI Change Meaningful Improvement% Combined Therapy 127 7.4 ± 1.5 2.5 ± 1.8 -5.0 ± 1.6 64.6 ± 19.2 48.7 ± 24.4 -15.9 ± 8.3 78.0% Exercise Therapy 164 7.4 ± 1.3 3.4 ± 2.0 -4.0 ± 1.5 66.2 ± 18.4 53.8 ± 23.6 -12.4 ± 8.5 55.5% Manual Therapy 11 7.8 ± 1.1 5.5 ± 1.4 -2.3 ± 1.3 70.7 ± 15.4 64.7 ± 17.7 -6.0 ± 4.0 0.0% Values are presented as mean ± standard deviation. VAS = Visual Analog Scale (0–10); ODI = Oswestry Disability Index (0-100). Negative change scores indicate improvement. All within-group changes were statistically significant (p < 0.001). Effect size analysis further supported these findings (Fig. 4 ). The combined therapy group showed large effects compared with manual therapy for both pain (d = 1.67) and disability (d = 1.23). Exercise therapy also produced large effects versus manual therapy (d = 1.14 for pain, d = 0.77 for disability). The comparison between combined and exercise therapy yielded medium effects for pain (d = 0.59) and small-to-medium effects for disability (d = 0.42). Clinically meaningful improvements (≥ 2 points for VAS AND ≥ 10 points for ODI) were achieved in 78% of patients receiving combined therapy, 55% of those receiving exercise therapy, and 0% of those receiving manual therapy (Table 2 ). To strengthen the clinical interpretation of the findings, the relative treatment effects were further expressed in absolute measures, applying a conservative definition that required both a clinically meaningful reduction in pain (≥ 2 points on the VAS) and a functional improvement of at least 10 points on the ODI. Under this criterion, combined therapy demonstrated an absolute risk difference of 22.5 percentage points when compared with exercise therapy (78.0% vs. 55.5%; 95% CI: 11.9 to 33.1), which translates into a number needed to treat (NNT) of 4. This indicates that for every four patients managed with combined therapy rather than exercise therapy alone, one additional patient is expected to achieve meaningful gains in both pain relief and functional status. The benefit of combined therapy over manual therapy was very large, with an absolute risk difference of 78.0 percentage points (78.0% vs. 0.0%; 95% CI: 70.3 to 85.7). This gave a number needed to treat (NNT) of 1. Exercise therapy was also better than manual therapy, with an absolute risk difference of 55.5 percentage points (55.5% vs. 0.0%; 95% CI: 47.4 to 63.6) and an NNT of 2. More details can be found in Table S5 of the Supplementary Materials. 4.3 Multivariable and Sensitivity Analysis The baseline characteristics were similar across all treatment groups, with no significant differences between them (Table S3, Supplementary). Multivariable linear regression models were used, adjusting for age, gender, BMI, baseline VAS, and baseline ODI. The results confirmed the primary findings. The adjusted treatment effects stayed statistically significant and clinically meaningful, with less than 0.15 points difference from the unadjusted values. The model explained 16.6% of the variance in VAS pain change scores (R² = 0.166), showing that confounding factors had minimal impact (Table 3 ). Table 3 Unadjusted vs. Confounder-Adjusted Treatment Effects for VAS Pain Change Comparison Unadjusted Estimate (95% CI) Adjusted Estimate (95% CI) Change Combined vs Exercise Therapy −0.97 (− 1.33 to − 0.60)*** −0.83 (− 1.18 to − 0.48)*** + 0.13 Combined vs Manual Therapy −2.68 (− 3.52 to − 1.84)*** −2.64 (− 3.48 to − 1.80)*** + 0.04 Exercise vs Manual Therapy −1.72 (− 2.55 to − 0.88)*** −1.81 (− 2.64 to − 0.98)*** −0.09 Values are mean differences in VAS pain change scores. Negative values indicate greater improvement in the first group listed. Adjusted estimates are controlled for age, sex, BMI, baseline VAS, and baseline ODI. ** p < 0.001. The sensitivity analyses used multiple imputation, per-protocol, and last-observation-carried-forward methods. The results were almost the same in all cases, showing that the findings were strong even with different ways of handling missing data (Table 4 ). Table 4 Sensitivity Analysis of Treatment Effects Analysis Method Combined vs Exercise (VAS) Combined vs Manual (VAS) p-value Complete Case (Primary) -0.9 (-1.3 to -0.6) -2.7 (-3.5 to -1.8) < 0.001 Worst Case Scenario -0.9 (-1.3 to -0.6) -2.7 (-3.5 to -1.8) < 0.001 Best Case Scenario -0.9 (-1.3 to -0.6) -2.7 (-3.5 to -1.8) < 0.001 LOCF Analysis -0.9 (-1.3 to -0.6) -2.7 (-3.5 to -1.8) < 0.001 Values represent mean differences (95% confidence intervals). Negative values indicate greater improvement in the first group mentioned. ***p < 0.001 for all comparisons. 4.4. Secondary Outcomes Medication use decreased substantially in all groups, with the greatest reductions observed in the combined therapy group. NSAID use declined by 72.5% and opioid use by 97% in the combined therapy group, compared with smaller reductions in the exercise and manual therapy groups. Combined therapy also demonstrated the lowest recurrence rate of low back pain during follow-up (4.7% vs. 10.4% for exercise therapy and 18.2% for manual therapy; Table 5 , Fig. 5 ). Table 5 Secondary Outcomes by Treatment Group Treatment Group N NSAIDs Before NSAIDs After Opioids Before Opioids After Pain Recurrence Follow-up Median (IQR) Combined Therapy 127 89/127 (70.1%) 35/127 (27.6%) 36/127 (28.3%) 1/127 (0.8%) 6/127 (4.7%) 4.9 (2.9–6.4) months Exercise Therapy 164 123/164 (75.0%) 39/164 (23.8%) 43/164 (26.2%) 0/164 (0.0%) 17/164 (10.4%) 4.9 (2.7–6.2) months* Manual Therapy 11 9/11 (81.8%) 4/11 (36.4%) 4/11 (36.4%) 0/11 (0.0%) 2/11 (18.2%) 3.7 (1.6-5.0) months Values are presented as n (%) or median (IQR). NSAIDs = non-steroidal anti-inflammatory drugs. Combination medications were recoded into the predominant drug class for consistency. Exercise therapy group includes one extreme outlier (655.5 months). * The median follow-up duration was 8.3 months (IQR 6.5–10.2), which was comparable across treatment groups. Missingness for secondary outcomes was minimal and did not differ by group, supporting the validity of these results (Table 5 ). 4.5 Subgroup Analyses Subgroup analyses showed that baseline pain severity and BMI significantly modified treatment outcomes. Patients with severe baseline pain achieved greater improvements in both VAS and ODI scores than those with moderate pain (p = 0.008; Table 6 , Fig. 6). Table 6 Pain Category Analysis by Treatment Group Treatment Group N Moderate Pain n (%) Severe Pain n (%) Moderate Pain Change Moderate ODI Change Severe Pain Change Severe ODI Change Combined Therapy 127 33/127 (26.0%) 94/127 (74.0%) -4.5 -18.2 -5.2 -15.1 Exercise Therapy 164 43/164 (26.2%) 121/164 (73.8%) -3.7 -15.8 -4.1 -11.1 Manual Therapy 11 1/11 (9.1%) 10/11 (90.9%) -1.0 -2.0 -2.4 -6.4 Values are presented as n (%) or mean change scores. Negative values indicate improvement. Similarly, patients with BMI < 30 demonstrated greater functional gains compared with obese patients, particularly for ODI improvement (p = 0.003; Table 7 , Fig. 7 ). Table 7 Treatment Effectiveness by BMI Category BMI Category N Overall Pain Change Overall ODI Change Best Treatment Best Pain Improvement Treatment Ranking Normal 71 -4.3 ± 1.7 -15.4 ± 9.9 Combined Therapy 4.4 points CT: 4.4 > ET: 4.3 > MT: 1.5 Overweight 106 -4.5 ± 1.6 -14.3 ± 8.3 Combined Therapy 5.3 points CT: 5.3 > ET: 3.9 > MT: 2.8 Obese 85 -4.3 ± 1.7 -11.0 ± 7.1 Combined Therapy 4.8 points CT: 4.8 > ET: 3.9 > MT: 2.3 Values are presented as mean ± standard deviation. CT = Combined Therapy; ET = Exercise Therapy; MT = Manual Therapy. Negative values indicate improvement. In contrast, treatment effects were consistent across age groups and gender, with no statistically significant interaction effects (p = 0.080 and p = 0.454, respectively; Table S4, Supplementary; Fig. 8 ). 5. Discussion This study gives strong real-world evidence that combining manual therapy with exercise therapy is superior to either modality alone for chronic low back pain (CLBP). The results confirm that combined care improves both pain and function reflecting the advantage of a multimodal approach, including reduced medication reliance and lower recurrence rates. These findings strongly support the use of combined therapy in clinical practice and help fill important gaps in the current evidence. 5.1. Primary Outcomes and Clinical Significance The primary result of this study confirmed that combined therapy produce meaningful improvements in both pain and disability, demonstrated reduction in Pain by 5.0 points on the VAS, and improvement in disability by 15.9 points on the ODI. These changes were much greater than the established MCID thresholds [ 32 , 35 , 36 ]. This provides strong real-world support for recent high-quality studies. For example, the review by Narenthiran and others [ 7 ] showed that 8 out of 10 studies found benefits when manual therapy was added to exercise. Our results strongly confirm this. The size of improvement in our combined therapy group (78% achieving meaningful improvement in both pain and disability) was almost the same as the trial by Blanco-Giménez and others [ 37 ], which showed 87.7% improvement with combined therapy compared to 27.1% with exercise alone. The effect sizes for combined therapy compared to manual therapy alone were very large (d = 1.67 for pain, d = 1.23 for disability). Based on Cohen’s guidelines [ 38 ], these values are in the “large” range. This means the differences are clinically important and bring great improvements in patients’ quality of life. In most studies, treatments usually give only small or moderate improvements in pain and disability [ 4 , 5 ]. Our results show that combining manual and exercise therapy can create stronger effects in real-world practice. 5.2. Mechanisms of Action The superior results in the exercise therapy and combined therapy groups may be due to the different ways manual therapy and exercise therapy work. Manual therapy methods, such as mobilization and manipulation, are thought to give short-term pain relief [ 28 ]. Those techniques affecting pain through mechanical and nerve pathways and by improving movement in the spine, which helps patients return to activity sooner. In contrast, exercise therapy gives longer-lasting improvement. It works by reducing deconditioning, improving motor control, and addressing psychosocial factors related to long-term pain. Systematic Reviews have shown that the benefits of exercise continue even after treatment ends, with steady improvements in pain and function in the short, intermediate, and long term [ 5 , 29 ]. Together, these effects suggest that manual therapy and exercise work best when combined. Manual therapy helps by giving quick pain relief and better movement, which makes it easier for patients to take part in exercise. Exercise then builds on this progress and keeps the recovery going. This teamwork between the two approaches likely explains why combined therapy gives better results than using only one treatment [ 5 , 28 ]. 5.3. Secondary Outcomes: Comprehensive Treatment Benefits 5.3.1. Medication Reduction An important result of this study is that combined therapy reduced the need for medicine more than single treatments. NSAID use reduced by 72.5% and opioid use by 97.2%. These reductions were much greater than those seen with either therapy alone. The reduction in opioid use is very large, but it should be read with ccautious because the number of opioid users in each group was small. The reduction in NSAID use was seen in larger groups, so it is more reliable and likely to be clinically important. These results align with other studies showing that non-drug treatments can lower the need for medicine. For example, early physical therapy has been linked to less opioid and non-opioid use at discharge [ 39 ]. Manual therapy has also been linked to less tramadol use over one year in adults with new low back pain [ 40 ]. In another trial, aerobic exercise gave pain relief similar to morphine before treatment [ 41 ]. The medication reduction in our study also matches the findings of Gedin and others [ 9 ], who found that combined therapy gave lower direct healthcare costs and the best QALY gains compared with single treatments. Their study did not look at medication use directly, but the lower costs may partly be due to less need for medicine as well as fewer other healthcare costs. 5.3.2. Pain Recurrence Prevention A key result in our study is the significant lower pain recurrence with combined therapy (4.7%) compared with exercise therapy (10.4%) and manual therapy (18.2%). This is an important long-term outcome. Recurrent low back pain is linked to greater disability, longer absence from work, and greater healthcare and social costs [ 42 , 43 ]. In general, low back pain is one of the main causes of limited activity and economic burden worldwide [ 44 ]. Our results on recurrence rate with evidence that exercise can reduce relapse risk. A Cochrane review summarized by Roren and others [ 45 ] reported around a 50% reduction in 1-year recurrence compared with no treatment. Still, results in the wider literature are mixed. The TOPS trial found that exercise plus education did not reduce recurrence compared with an education booklet [ 43 ]. Koumantakis and others [ 11 ] also reported no added benefit when stabilization was added to general exercise for recurrent low back pain, although subgroup analyses suggested possible reductions. Despite these mixed results, the very low recurrence in our combined therapy group suggests that structured multimodal care may offer an advantage. 5.4. Subgroup Analysis: Personalized Treatment Insights Our subgroup analysis showed that all patients improved, but some groups had larger benefits. The biggest differences were seen in baseline pain severity and body mass index. Patients with severe pain at baseline gained significantly greater than those with moderate pain (p = 0.008). This suggests that intensive multimodal approach may be most useful for severe cases. These results differ from earlier studies, which found that milder cases often improved more [ 29 , 32 ]. In terms of BMI, overweight patients (25–29.9) had the best disability improvement, while obese patients (≥ 30) showed smaller gains. This supports earlier evidence that obesity can limit physiotherapy outcomes [ 46 ]. In contrast, age and gender had little effect. Younger patients showed slightly better results, likely due to better healing and fewer comorbidities [ 44 , 47 ]. However, these differences were not statistically significant. Both men and women improved in a similar way with combined therapy. This aligns with previous systematic reviews and guidelines, which found no important gender differences in low back pain outcomes [ 3 , 29 ]. These results suggest that baseline severity and BMI are the most important factors that change how patients respond to treatment. Age and gender seem to have little effect. Rehabilitation plans that focus on these patient factors, especially extra support for obese patients, may help improve outcomes in chronic low back pain. 5.5. Comparison with Previous Research and Clinical Guidelines Our results support and extend the current evidence for multimodal approaches in chronic low back pain. The systematic review by González-Gómez and others [ 4 ] showed no clear difference between manual therapy and exercise therapy when used alone. In contrast, our study showed that combined therapy was clearly better than either single treatment. This provides real-world support for clinical practice guidelines, such as those from the American College of Physicians, which now recommend multimodal care for chronic low back pain. Moreover, our results contrasted the earlier study by Hsieh and others [ 48 ], that showed no benefit of combined therapy compared to single treatments in patients with subacute pain. The difference may be because our study focused on chronic patients, had a larger sample size, and used real-world clinical data that reflects normal practice. Although, our study focused only on physical treatments, current guidelines [ 2 ] also highlight the importance of psychological care, such as cognitive behavioural therapy (CBT). Evidence shows that CBT gives small but steady benefits in lowering pain, disability, and emotional distress in people with chronic pain [ 49 ]. Our results show that physical multimodal approaches effective, but future studies should test if adding psychological care to combined therapy can give even better results. 5.6. Clinical Implications and Implementation 5.6.1. Robust Statistical Analysis and Confounding Control One strength of this study is that the treatment groups were balanced, with no significant differences in age, gender, BMI, or pain scores (all p > 0.05). This balance makes the results more reliable because it reduces the chance of bias. In addition, when we used regression analysis to adjust for possible confounders, the results were almost the same as the unadjusted results, with less than 0.15 points difference on the VAS scale. This shows that the findings are strong and not likely to change because of hidden factors. Giving both adjusted and unadjusted results also increases clarity and follows the STROBE guidelines for observational studies. 5.6.1. Treatment Protocol Development The strong results of combined therapy in different outcomes domains supports the development of standardized multimodal treatment protocols for chronic low back pain. These protocols should include both manual therapy and structured exercise programs. The level and length of treatment can then be adjusted depending on the baseline of pain severity at the start. 5.6.2. Healthcare Resource Allocation The cost-effectiveness of our results is important. While Combined therapy may need more resources, the superior outcomes in pain reduction, functional improvement, medication reduction, and recurrence prevention likely result in overall healthcare cost savings through reduced long-term healthcare utilization. This aligns with trial evidence showing that combination therapy offers superior cost-effectiveness compared with exercise or manual therapy alone [ 9 ], and with epidemiological data showing low back pain creates a high economic burden on healthcare systems worldwide [ 44 ]. 5.6.3. Patient Education and Expectations The wide benefits of combined therapy, such as reducing medication use and lowering recurrence rate, are important points for patient education. Patients can be advised that using more than one type of treatment not only gives better pain relief but also helps them depend less on medicine and avoid future episodes. From a clinical counseling perspective, patients can also be informed that combined therapy provides approximately a 72% chance of achieving meaningful improvement in both pain and function, compared with about 50% with exercise therapy alone. For clinicians, this translates to treating four patients with combined therapy instead of exercise therapy alone to achieve one additional successful outcome (NNT = 4). 5.7. Limitations and Statistical Considerations Several limitations should be considered when interpreting these results: Confounding and Causal Inference This study used a retrospective design, which may allow unmeasured confounding to affect the results. Still, several factors strengthen causal inference in this study. First, the treatment groups baseline were balanced in all measured characteristics (all p > 0.05), suggesting minimal confounding by indication. Second, while carrying out multivariable adjustment for key confounders such as age, gender, BMI, and baseline scores, the results stayed almost the same as the unadjusted ones (less than 0.15 VAS points difference). This shows that the measured confounders did not bias the results. However, other unmeasured confounders like patient motivation, therapist skill, or treatment attendance may still play a role and limit how strong the conclusions are. Statistical Power and Manual Therapy Group Size One important limitation of this study is the very small size of the manual therapy group (n = 11). This makes it difficult to detect real differences and increases the chance of error. Under the conservative definition of clinically meaningful improvement (≥ 2-point VAS and ≥ 10-point ODI), none of the manual therapy patients achieved both thresholds. This striking result should be interpreted with caution, as the group was underpowered (post-hoc power ~ 30%) and may underestimate the true potential benefit of manual therapy. This means that the large effect size differences observed between manual therapy and the other groups could be overstated because of the small number of patients. Future studies should include at least 30 patients in each group to reach proper power (80%) and allow stronger comparisons. Missing Data and Robustness of Findings A strength of this study is that outcome data were almost complete, with only 1.3% missing VAS scores and 2.0% missing ODI scores. Comprehensive sensitivity analyses using different assumptions for missing data (worst-case scenario, best-case scenario, and last observation carried forward) gave the same results as the main analysis. This shows that the results are robust and do not depend on missing data handling assumptions. The very small amount of missing data also lowers the chance of bias from differential dropout patterns across treatment groups. Generalizability (External Validity) The results of this study are likely generalizable to adult patients with non-specific chronic low back pain who are treated on similar tertiary care hospitals. This is most relevant for patients with similar demographics, such as a mean age of about 46 years and with 62% being female, and who have access to both manual and exercise therapy. However, there are some factors that may reduce how much the results can be applied to other settings. (1) Healthcare Setting - Results may be different in primary care, where treatment methods, therapist skills, and patient selection are not the same; (2) Geographic and Cultural Factors - This study was done in a Middle Eastern hospital, so cultural views on pain and treatment may affect outcomes in other regions; (3) Treatment Standardization- The specific manual therapy and exercise protocols used may not be universally available across different healthcare systems; (4) Patient Selection- The study included patients who completed at least four treatment sessions, potentially representing a more motivated population compared to typical clinical practice; (5) Healthcare Resources - In places with limited resources, it may be difficult to provide combined therapy. Healthcare providers should consider local patient characteristics, available resources, and treatment protocols when applying these findings. Future multi-center studies across diverse healthcare settings would strengthen the evidence base for generalizability. Follow-up Duration Variability Another limitation of this study is the presence of extreme outliers in follow-up duration. For example, one patient had a follow-up period of 655.5 months. Although this did not change the median follow-up time, it shows the challenges of using retrospective data. This problem highlights the need for future prospective studies with standardized follow-up protocols. In addition, while many secondary outcomes were analyzed, some important measures such as return to work, healthcare use, and patient satisfaction were not available in the electronic health records. Including these outcomes in future studies would provide a more complete view of treatment effectiveness. 5.8. Future Research Directions Based on our results, there are several important directions for future research. First, large randomized controlled trials are needed to confirm these findings and to define the best treatment protocols for combined therapy. Second, studies with longer follow-up should be done to test if the benefits last over time and to find which factors are linked with sustained improvement. Third, future studies should test the optimal sequencing and timing of manual therapy and exercise components within combined programs. In addition, prospective studies should incorporate detailed recording of treatment intensity and session spacing, as the distribution of sessions (for example, concentrated within a few weeks versus spread over several months) may influence effectiveness.Fourth, research should also include economic studies to check if combined therapy is cost-effective in different healthcare systems and populations. Finally, future studies should explore the mechanisms underlying the superior effectiveness of combined therapy. This includes examining the role of neurophysiological, biomechanical, and psychological factors that may explain the success of this approach. 5.9. Conclusion This study shows that using manual therapy and exercise therapy together works better than using each treatment alone for chronic low back pain. The combined approach not only reduced pain and improved function but also lowered the need for medication, reduced recurrence, and worked well in different patient groups. These benefits are likely because manual therapy helps with short-term pain relief, while exercise therapy gives longer-lasting functional improvement. The large effects seen, especially when comparing combined therapy with manual therapy alone, show clinically significant improvements in patient outcomes. The reductions in medication use and recurrence also suggest that this approach may save healthcare costs and guide future clinical recommendations. However, these findings should be viewed with caution because of the retrospective design, single-center setting, and the small sample size in the manual therapy group. Even with these limits, the study strongly supports combined therapy as a first-line option for chronic low back pain. Future studies should examine these results in large randomized controlled trials, consider the optimal sequencing of manual and exercise interventions, and explore mechanisms underlying treatment success across diverse populations. Declarations Author Contributions Conceptualization: Yazeed Timraz and Ali Sahari Methodology: Yazeed Timraz , Faisal Alotaibi , and Shouq Almutairi Data Curation: Ali Sahari, Faisal Alotaibi , Shouq Almutairi, Ahmed Hammami , Amal Alsaad , Fay Almehrej , Mayyer Alanazi , Reem Aldosary , Thikra Alotaibi Formal analysis: Yazeed Timraz and Rahaf Bin Salamah Software: Yazeed Timraz Validation: Ahmed Hammami and Amal Alsaad Investigation: Ali Sahari , Faisal Alotaibi, Shouq Almutairi , Ahmed Hammami , Amal Alsaad , Fay Almehrej, Mayyer Alanazi , Reem Aldosary and Thikra Alotaibi Writing—original draft preparation: Yazeed Timraz Writing—review and editing: Yazeed Timraz , Ali Sahari, Faisal Alotaibi , and Homoud Rajab Visualization: Fay Almehrej Supervision: Yazeed Timraz and Homoud Rajab Project administration: Yazeed Timraz Resources: Homoud Rajab All authors have read and agreed to the published version of the manuscript. Funding: This study received no external funding. The research was conducted as part of institutional academic activities. The sponsor had no role in study design, data collection, analysis, interpretation, or manuscript preparation. Institutional Review Board Statement: Human Ethics and Consent to Participate declarations: The study protocol was approved by the Institutional Review Board of King Abdullah International Medical Research Center (IRB #00000169625). The IRB granted a waiver of individual informed consent due to the retrospective, de-identified nature of the data. All procedures were conducted in accordance with the Declaration of Helsinki. Consent to Participate Not applicable. Individual consent was waived by the IRB. Clinical Trial Number Not applicable. This was a retrospective cohort study and not a clinical trial. Trial Registration Not applicable. This study was not prospectively registered as a clinical trial. Data Availability: The anonymized dataset was made available to editors and reviewers during peer review. It is not publicly archived but may be obtained from the corresponding author upon reasonable request and with appropriate ethical approval. Acknowledgments: The authors thank the rehabilitation therapists who generously contributed their time and expertise. We are also grateful to the Rehabilitation Department at the Ministry of National Guard–Health Affairs for facilitating data collection and access to clinical areas. Conflicts of Interest: The authors declare no conflicts of interest, financial or non-financial. AI Declaration: AI tools, such as ChatGPT, were used only to edit language and paraphrase text to make it clearer and grammatically correct. The design of the study, data collection, analysis, and interpretation were all completed fully by the authors. References Awaji, M. A. Epidemiology of low back pain in Saudi Arabia. J. Adv. Med. Pharm. Sci. 6 (4), 1–9. 10.9734/JAMPS/2016/24173 (2016). National Institute for Health and Care Excellence. 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Timraz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYBAC+8NQBj8QM0OYCfi1sEGVMUg2EK0FxjA4QLQWdu60Dz/+HJY3vnb28OuCGoZofvYE5g8/8DqMd/PMHp7Dhttu56VZzzjGkDuz5wGbZA8BLQw8EocZt93OMTPmYWPI3XAjgY2Bh4AWxj8Gh+03zwZp+ceQu/9GAvPHPwS0MPMkHE7cIJ1j/Ji3DWiLRAKDNCFbmGUOpCfPADqMmbdPInfGmYdt0jL4tPCf3cz45o+1bf/sHOPPPN9scvvbkw9/fINHCxQ0g7VLMDAAEQNjA2ENDAx1IIL5AzFKR8EoGAWjYOQBAMDaSRo0VoPLAAAAAElFTkSuQmCC","orcid":"","institution":"Ministry of the National Guard-Health Affairs","correspondingAuthor":true,"prefix":"","firstName":"Yazeed","middleName":"","lastName":"Timraz","suffix":""},{"id":539702454,"identity":"ad5b5891-1606-453e-ab4e-9b38f534dd72","order_by":1,"name":"Ali Sahari","email":"","orcid":"","institution":"Ministry of the National Guard-Health 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07:13:54","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":116175,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/a440da2667df31b9649a9278.png"},{"id":95895882,"identity":"5b83256f-cb40-4788-8e74-b551b7feb6c9","added_by":"auto","created_at":"2025-11-14 07:16:56","extension":"xml","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":169744,"visible":true,"origin":"","legend":"","description":"","filename":"2bc082f2d4a4426793b11e007edb0a111structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/4e2026feb5a34cd3729bc5b5.xml"},{"id":96242971,"identity":"d76746e8-64c6-45aa-9824-3598cae835de","added_by":"auto","created_at":"2025-11-19 07:15:04","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":191907,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/206d402ef9af2a64f3861b5a.html"},{"id":96243239,"identity":"93446a6a-df6e-47df-94e4-9a5150194f2c","added_by":"auto","created_at":"2025-11-19 07:15:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":309996,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSTROBE Flow Diagram.\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003eThe flow diagram shows the selection process for patients with chronic low back pain at the Rehabilitation Department in National Guard Hospital between August 2023 and August 2024. Out of 379 patients assessed, 302 with complete outcome data were included in the final analysis. They were divided into three groups: combined therapy (manual therapy + exercise therapy, n = 127), exercise therapy only (n = 164), and manual therapy only (n = 11). The data quality was very good, with little missing outcome data (1.3% for VAS and 2.0% for ODI).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/7d04b1f194f9b1a647c0ea40.png"},{"id":96242660,"identity":"4d9af1c1-5235-48ee-a571-061e956b1468","added_by":"auto","created_at":"2025-11-19 07:13:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":219975,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePain Outcomes by Treatment Group.\u003c/strong\u003e\u003c/em\u003e The bar chart shows baseline and post-treatment pain scores (VAS 0–10) for each treatment group. The error bars show the standard deviation. Combined therapy gave the greatest pain reduction, followed by exercise therapy, and then manual therapy.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/234444ac6baded06c27c6f30.png"},{"id":96243103,"identity":"fd618cfc-cf72-472b-a515-cdfbd944c382","added_by":"auto","created_at":"2025-11-19 07:15:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":235779,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunctional Outcomes by Treatment Group.\u003c/strong\u003e\u003c/em\u003e The bar chart shows baseline and post-treatment disability scores (ODI 0–100) for each treatment group. The error bars show the standard deviation. Combined therapy gave the greatest improvement in function, followed by exercise therapy, and then manual therapy.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/0c5a408b8e002c397848dd21.png"},{"id":96241843,"identity":"65e6ab11-162e-4ca5-9a17-1a360f897269","added_by":"auto","created_at":"2025-11-19 07:11:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":170998,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEffect Sizes for Between-Group Comparisons.\u003c/strong\u003e\u003c/em\u003e Cohen’s d effect sizes for pairwise comparisons between treatment groups for both pain (VAS) and functional disability (ODI) outcomes. Effect sizes are interpreted as small (d = 0.2), medium (d = 0.5), or large (d = 0.8). Combined therapy showed large effect sizes compared to manual therapy and medium effect sizes compared to exercise therapy.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/0045d34dafa6acc56c928bdf.png"},{"id":95895873,"identity":"e7e9e975-7bcc-4e8b-a086-2aa36cd8a786","added_by":"auto","created_at":"2025-11-14 07:16:56","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":270920,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSecondary Outcomes by Treatment Group.\u003c/strong\u003e\u003c/em\u003e Four-panel visualization showing: (A) NSAIDs reduction percentage, (B) Pain recurrence rates, (C) Pain improvement by age group, and (D) Pain improvement by baseline severity. Combined therapy consistently showed superior outcomes across all measures.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/57fa2f4967ad7d3565893255.png"},{"id":96242341,"identity":"31bf69a2-a06b-4c12-9413-998cec1221b0","added_by":"auto","created_at":"2025-11-19 07:12:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/ba52d47ebf08feaf7c6e2d85.png"},{"id":95895877,"identity":"07d0a0fc-17dc-4704-81fc-d5b1a210381f","added_by":"auto","created_at":"2025-11-14 07:16:56","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":654531,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBMI Analysis and Treatment Effectiveness.\u003c/strong\u003e\u003c/em\u003e The figure has four panels: (A) BMI distribution by treatment group, (B) treatment results by BMI category, (C) the link between BMI and pain change, and (D) overall treatment response by BMI category. Combined therapy was the best across all BMI groups. Overweight patients showed the greatest improvement.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/da80851bc13b192ae9ffd564.png"},{"id":96242750,"identity":"0f8d0176-4bf2-4ff1-be2c-2b8e5f9ce9cf","added_by":"auto","created_at":"2025-11-19 07:14:13","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":196017,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eTreatment Effectiveness by Patient Subgroups.\u003c/strong\u003e\u003c/em\u003e \u003cem\u003eTwo-panel visualization showing pain improvement by: (A) Age group and treatment type, and (B) Baseline pain severity and treatment type. Combined therapy consistently showed superior outcomes across all subgroups.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/b9a454d8b99a66b0db071ead.png"},{"id":100548557,"identity":"384aea83-f483-423e-af84-903cd4bb7f4c","added_by":"auto","created_at":"2026-01-19 08:19:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4588810,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/1659528e-31b9-49ea-b34d-81de5f9bcf96.pdf"},{"id":96242687,"identity":"e4e0cfc0-4ccd-4cc4-a3f5-00944d0d76b8","added_by":"auto","created_at":"2025-11-19 07:14:04","extension":"zip","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":57750,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"supplemntryfile.zip","url":"https://assets-eu.researchsquare.com/files/rs-7720973/v1/4168a1f44751b2e13a3e2abb.zip"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Effectiveness of Manual Therapy, Exercise Therapy, and Combined Therapy for Chronic Low Back Pain: A Comprehensive Retrospective Cohort Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eChronic low back pain (CLBP) is one of the main causes of disability in the world. In Saudi Arabia, it is very common, with rates between 53.2% and 79.17% in different groups [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The condition is a big problem for health systems because it lasts a long time and costs a lot. Although many studies have been done, the best way to treat it without surgery or medicine is still not clear. Exercise therapy (ET) and manual therapy (MT) are usually advised as the first treatments. However, it is still debated whether one is better than the other or if using both together works best.\u003c/p\u003e\u003cp\u003eResearch shows that both exercise therapy (ET) and manual therapy (MT) can help reduce pain and disability. However, when used alone, neither is always better than the other. Guidelines such as those from NICE [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and the American College of Physicians [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] suggest that exercise should be the main part of treatment. Manual therapy is advised only when used together with exercise. This shows that single treatments give only small improvements, while combining methods may work better for the complex nature of CLBP.\u003c/p\u003e\u003cp\u003eBecause of these uncertainties, more research is needed to test how exercise therapy (ET) and manual therapy (MT) work alone and together. Most studies so far are randomized controlled trials with strict rules for who can take part, which makes it hard to apply the results to all patients. Real-world studies are needed to see how these treatments work in normal clinical practice. This study looks at the outcomes of ET, MT, and their combination in patients with chronic low back pain, focusing on pain, disability, recurrence, and medication use. The next section reviews the main studies on how these therapies compare.\u003c/p\u003e"},{"header":"2. Literature Review","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Equivalence of Single Interventions\u003c/h2\u003e\u003cp\u003eMany studies show that exercise therapy (ET) and manual therapy (MT) give similar results when used alone for chronic low back pain (CLBP). A recent review and meta-analysis by Gonz\u0026aacute;lez-G\u0026oacute;mez and others [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which included six trials with 743 patients, found no clear difference between ET and MT overall. However, ET showed a small long-term benefit for reducing disability (SMD \u0026minus;\u0026thinsp;0.25, 95% CI \u0026minus;\u0026thinsp;0.43 to \u0026minus;\u0026thinsp;0.07). The strength of this evidence was rated very low because of the small number of patients and differences between the studies.\u003c/p\u003e\u003cp\u003eA Cochrane review by Hayden and others [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], which included 249 trials with 24,486 participants, found that exercise therapy (ET) works better than no treatment, usual care, or placebo. ET reduced pain (MD \u0026minus;\u0026thinsp;15.2/100) and improved function (MD \u0026minus;\u0026thinsp;6.8/100). However, when ET was directly compared with manual therapy (MT), there were no major differences in pain (MD 1.0, 95% CI \u0026minus;\u0026thinsp;3.1 to 5.1) or in functional outcomes.\u003c/p\u003e\u003cp\u003eEvidence from Gomes-Neto and others [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] also shows that exercise and manual therapy (MT) give similar results. Stabilization exercises reduced pain and disability to the same level as MT, with no clear differences between the groups. However, stabilization exercises worked better than general exercise in some outcomes.\u003c/p\u003e\u003cp\u003eOverall, the findings show that exercise therapy (ET) and manual therapy (MT) work equally well when used alone, with no strong evidence that one is better than the other. This means that the choice between them often depends on patient preference, the skills of the clinician, and what resources are available, rather than clear proof of one being more effective. Because of this, more studies are now looking at whether combining ET and MT can give better results.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Superiority of Combined Approaches\u003c/h2\u003e\u003cp\u003eSome studies show that combining manual therapy (MT) with exercise therapy (ET) may give better results for chronic low back pain (CLBP), but the evidence is not consistent. A recent review of 10 trials found that ET\u0026thinsp;+\u0026thinsp;MT improved pain and disability in the short term, but the studies were very different from each other and did not give strong long-term results [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Small trials also showed that ET\u0026thinsp;+\u0026thinsp;MT reduced pain and disability within six weeks [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Another larger trial did not find significant clinical differences between groups but showed that combined care might save costs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Overall, ET\u0026thinsp;+\u0026thinsp;MT seems to give useful short-term benefits and may reduce costs, but the results are mixed. More large, high-quality studies are needed to know if the benefits last and if the combined approach is truly cost-effective. To understand this better, it is also important to look at the limits of using ET and MT alone.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Limitations of Isolated Interventions\u003c/h2\u003e\u003cp\u003eAlthough exercise therapy (ET) and manual therapy (MT) are helpful, using them alone has clear limits. A recent review on isolated lumbar extension (ILEX) training showed that it reduced pain (ES \u0026minus;\u0026thinsp;0.63, p\u0026thinsp;=\u0026thinsp;0.004), but it did not improve disability or strength, with the certainty of this evidence rated very low [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In another study, Koumantakis and others [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] found that adding stabilization training to a general exercise program did not improve outcomes for people with recurrent low back pain. In fact, general exercise alone gave better short-term results for reducing disability.\u003c/p\u003e\u003cp\u003eOverall, the evidence shows that exercise or manual therapy alone can give some benefits, but these are often small, uncertain, or do not last long. This supports the idea of using a combined approach, such as exercise therapy (ET) with manual therapy (MT), which may give stronger and longer-lasting results. The history of research on low back pain also shows that there are still many gaps in evidence, and these continue to make clinical practice difficult.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Historical Perspective and Evidence Gaps\u003c/h2\u003e\u003cp\u003eEarly trials gave useful background for how conservative treatments developed for chronic low back pain (CLBP). The results were mixed. Some studies showed benefits for manual therapy, others supported combined care, while some found no clear differences [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Overall, these studies showed that outcomes varied, and pain relief did not always lead to long-term functional improvement.\u003c/p\u003e\u003cp\u003eRecent studies have also shown mixed results. Extra methods, such as myofascial release and Mulligan mobilization, did not give clear extra benefits when added to spinal manipulation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This suggests that adding more passive treatments does not always lead to better outcomes.\u003c/p\u003e\u003cp\u003eSystematic Reviews have tried to bring this evidence together. Coulter and others [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] found moderate-quality evidence that spinal manipulation and mobilization can slightly reduce pain and improve function, but the results of the trials were too different to be fully certain. A Cochrane review by Rubinstein and others [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] also showed that spinal manipulation gave results similar to other recommended treatments such as exercise, with only small short-term benefits.\u003c/p\u003e\u003cp\u003eEven with these reviews, many questions remain. Strategies that target subgroups have not given consistent benefits [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The best way to combine treatments, the right dosage, and how long the effects last are still unclear. From a cost view, Gedin and others [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] ran a trial comparing physiotherapy, chiropractic care, their combination, and advice, these are not the same as standard ET or MT, but the results suggested that the combined care might be more cost-effective. However, the trial was too small to be sure, so the results should be read with caution.\u003c/p\u003e\u003cp\u003eIn summary, single treatments give only small benefits. Combined approaches may help in the short term, but their long-term value for patients and costs is still not clear. This gap is more obvious in Saudi Arabia, where ET and MT are often used together, but there are limited local controlled trials [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This shows the need for large real-world studies that directly compare ET, MT, and their combination. These studies should look at important outcomes such as pain, disability, recurrence, and use of medicine. The current study was designed to fill this gap.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Methodology","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Study Design\u003c/h2\u003e\u003cp\u003eThis study used a retrospective cohort design to compare three treatments for chronic low back pain (CLBP): manual therapy (MT), exercise therapy (ET), and a combination of both (MT\u0026thinsp;+\u0026thinsp;ET). The patients were taken from those who received outpatient physiotherapy for non-specific CLBP at the Rehabilitation Department in National Guard Hospital between August 2023 and August 2024. This design was chosen to test how these treatments work in real clinical practice, using data collected from electronic health records (EHR). The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Study Population\u003c/h2\u003e\u003cp\u003eThe study included adult patients (18 years and older) who had non-specific chronic low back pain (CLBP) and started treatment at the outpatient physical therapy department during the study period.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion criteria\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eAge 18 years or older.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDiagnosis of non-specific CLBP, defined as pain lasting more than 3 months, based on the NIH Task Force recommendations [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCompletion of at least four treatment sessions of MT, ET, or MT\u0026thinsp;+\u0026thinsp;ET.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAt least one pre-treatment and one post-treatment outcome recorded in the EHR.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eExclusion criteria\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eLow back pain from specific causes such as fracture, tumor, infection, inflammatory conditions, radiculopathy, or spinal stenosis, as defined in the European guidelines [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePrevious spinal surgery.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePregnancy.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAny condition that the treating clinician judged as unsafe for the interventions.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Interventions\u003c/h2\u003e\u003cp\u003ePatients were placed into three groups based on the treatments recorded in the EHR: manual therapy (MT), exercise therapy (ET), or a combination of both (MT\u0026thinsp;+\u0026thinsp;ET).\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eManual Therapy (MT)\u003c/b\u003e: This group included patients who received treatments such as joint mobilization, manipulation, soft tissue massage, and myofascial release. These techniques are part of standard physiotherapy practice [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eExercise Therapy (ET)\u003c/b\u003e: This group included patients who followed exercise programs such as strengthening, stretching, motor control training, and aerobic exercises. These programs were based on evidence-based guidelines [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eCombined Therapy (MT\u0026thinsp;+\u0026thinsp;ET)\u003c/b\u003e: This group included patients who received both manual therapy (MT) and exercise therapy (ET) during their treatment. The order or proportion of each treatment was not restricted.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThe groups were defined using the \"TherapyType\" variable in the EHR. Information about how the care was given, including the frequency, duration, and techniques used in each group, was also collected.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Outcome Measures\u003c/h2\u003e\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\u003ch2\u003e3.4.1. Primary Outcomes\u003c/h2\u003e\u003cp\u003eThe main outcomes were pain and functional disability. These were measured at the start of treatment and after treatment.\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePain Intensity\u003c/b\u003e: Measured with the Visual Analog Scale (VAS). A score of 0 means \u0026ldquo;no pain\u0026rdquo; and 10 means \u0026ldquo;worst pain.\u0026rdquo; The VAS is a reliable tool to measure pain [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eFunctional Disability\u003c/b\u003e: Measured with the Oswestry Disability Index (ODI). This 10-question tool measures how low back pain affects daily life. Scores range from 0 (no disability) to 100 (worst disability). The ODI is a standard and valid tool [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eA change of at least 2 points (MCID) on the VAS and 10 points on the ODI was used to define meaningful improvement, based on published recommendations [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003e3.4.2. Secondary Outcomes\u003c/h2\u003e\u003cp\u003eThe secondary outcomes were:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMedication use\u003c/b\u003e: Use of pain medicine before and after treatment. This included NSAIDs, opioids, acetaminophen, or combined drugs. If a combination was used (such as NSAIDs with muscle relaxants), it was counted under the main drug type.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePain recurrence\u003c/b\u003e: The number of patients who needed more treatment for low back pain during follow-up.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eFollow-up duration\u003c/b\u003e: The time in months from the end of treatment to the last visit recorded.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eTreatment adherence\u003c/b\u003e: The number of sessions completed compared with the number of sessions prescribed.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\u003ch2\u003e3.4.3. Pain Categorization\u003c/h2\u003e\u003cp\u003ePain severity was grouped using VAS scores. A score of 1\u0026ndash;4 meant mild pain, 5\u0026ndash;6 meant moderate pain, and 7\u0026ndash;10 meant severe pain. These cutoffs have been shown in many studies to work well for identifying how pain affects function [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The 11-point numeric rating scale is also a reliable and sensitive tool for measuring chronic pain [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.5. Data Extraction\u003c/h2\u003e\u003cp\u003eData were taken from the EHR using a standard form to keep results consistent. The data included:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePatient details\u003c/b\u003e: Age, gender, and BMI.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eClinical details\u003c/b\u003e: How long symptoms lasted, history of low back pain, and baseline pain category.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eTreatment details\u003c/b\u003e: Treatment group (MT, ET, or MT\u0026thinsp;+\u0026thinsp;ET), number of sessions, and length of care.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e: VAS and ODI scores before and after treatment, medication use, pain recurrence, and follow-up time.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eTo make sure the data were reliable, all reviewers were trained in the same way. Reliability was tested on 10% of the sample. Agreement was very high for the main outcomes (VAS ICC\u0026thinsp;=\u0026thinsp;0.94; ODI ICC\u0026thinsp;=\u0026thinsp;0.91) and for other key data such as treatment type (κ\u0026thinsp;=\u0026thinsp;0.89) and medication use (κ\u0026thinsp;=\u0026thinsp;0.86). Any disagreements were discussed and solved with a third reviewer if needed.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e3.6. Statistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using Python (version 3.11) with the pandas, numpy, scipy, and matplotlib libraries. A two-tailed significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was used for all tests.\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eDescriptive Analysis and Baseline Comparisons\u003c/b\u003e: Descriptive statistics (means, standard deviations, frequencies, and percentages) were used to summarize patient characteristics. To assess baseline comparability between the three treatment groups, one-way ANOVA was used for continuous variables (e.g., age, baseline VAS) and chi-square tests were used for categorical variables (e.g., gender).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePrimary and Secondary Outcome Analysis\u003c/b\u003e: The primary analysis was a complete case analysis. Change scores (post-treatment minus baseline) were calculated for VAS and ODI. A one-way ANOVA was used to compare the mean change scores between the three treatment groups. If the overall test was significant, pairwise comparisons were conducted using t-tests with appropriate correction for multiple comparisons. Cohen's d was calculated to determine the effect size of the differences. For secondary outcomes, chi-square tests were used for categorical variables (medication use, recurrence) and ANOVA for continuous variables (follow-up duration).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eSubgroup and Sensitivity Analyses\u003c/b\u003e: To explore potential effect modifiers, pre-planned subgroup analyses were conducted by stratifying patients by age, gender, baseline pain severity, and BMI. The robustness of the findings was assessed through sensitivity analyses, including multiple imputation for missing data (see Section \u003cspan refid=\"Sec20\" class=\"InternalRef\"\u003e3.10\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e3.7. Confounding and Statistical Adjustment\u003c/h2\u003e\u003cp\u003eTo control for potential confounding and estimate adjusted treatment effects, multivariable linear regression models were developed for the primary outcomes (change in VAS and ODI scores). Potential confounders were identified a priori and included age, gender, BMI, and baseline VAS and ODI scores. In the models, the treatment group was the primary independent variable (with manual therapy as the reference group), and the aforementioned confounders were included as covariates. Both unadjusted and adjusted treatment effect estimates, along with their 95% confidence intervals, were calculated. Model assumptions were checked via residual analysis, and model fit was assessed using R-squared values.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e3.8. Addressing Potential Sources of Bias\u003c/h2\u003e\u003cp\u003eSeveral steps were taken to reduce bias. To avoid selection bias, the inclusion and exclusion criteria were applied strictly to all patients in the study. Information bias was reduced by using a standard data collection process and by confirming high agreement between reviewers (see Section \u003cspan refid=\"Sec15\" class=\"InternalRef\"\u003e3.5\u003c/span\u003e). Using structured EHR data helped prevent errors in classifying treatments. Outcomes were taken from recorded data instead of patients, which reduced recall bias. Missing data were checked using complete case analysis and tested further in sensitivity analyses.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003e3.9. Sample Size Calculation\u003c/h2\u003e\u003cp\u003eA sample size calculation was done before the study for the primary outcome (change in VAS scores). To find a medium effect size (f\u0026thinsp;=\u0026thinsp;0.25) with 80% power and a significance level of 0.05 in a one-way ANOVA with three groups, at least 159 patients (53 in each group) were needed. The calculation was done using G*Power. The final study included 302 patients, which was more than the required number. A post-hoc analysis showed that the power was greater than 0.90 for finding the differences in VAS change scores.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003e3.10. Sensitivity Analysis\u003c/h2\u003e\u003cp\u003eTo assess the robustness of the primary findings, three sensitivity analyses were planned:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMultiple Imputation\u003c/b\u003e: To handle missing data, the main analysis was repeated using datasets created with multiple imputation by chained equations (MICE).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePer-Protocol Analysis\u003c/b\u003e: This analysis included only patients who finished all treatment sessions to test the effect of treatment adherence.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eAlternative Model\u003c/b\u003e: The analysis was repeated with a different statistical model to check if the results stayed consistent.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThe results of these analyses were compared to the primary findings to evaluate the stability of the conclusions.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003e3.11. Ethical Considerations\u003c/h2\u003e\u003cp\u003e The study protocol was approved by the Institutional Review Board of King Abdullah International Medical Research Center (IRB #00000169625) and adhered to the principles of the Declaration of Helsinki. The IRB granted a waiver of informed consent due to the retrospective and use of de-identified nature of the data. To ensure confidentiality, all patient data were anonymized and stored on a secure server with access restricted to the research team.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Results","content":"\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\u003ch2\u003e4.1. Participant Characteristics and Study Flow\u003c/h2\u003e\u003cp\u003eA total of 379 patients with chronic low back pain were found during the study period. After applying the eligibility criteria, 302 patients (79.7%) were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The main reasons for exclusion were specific spinal problems (n\u0026thinsp;=\u0026thinsp;8), previous spinal surgery (n\u0026thinsp;=\u0026thinsp;4), pregnancy (n\u0026thinsp;=\u0026thinsp;2), missing therapy data (n\u0026thinsp;=\u0026thinsp;33), and incomplete outcome measures (n\u0026thinsp;=\u0026thinsp;30).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe data were almost complete. Post-treatment pain scores (VAS) were available for 98.7% of patients, and disability scores (ODI) for 98.0%. The missing data were very small, random, and showed no clear differences between groups (Table S2, Supplementary). Baseline characteristics were also similar between the patients included and those excluded, showing that the final cohort was representative (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, Supplementary).\u003c/p\u003e\u003cp\u003eBaseline demographic and clinical characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The three treatment groups were similar in age, sex, BMI, and symptom duration (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Overall, patients had a mean age of 45.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9 years, were predominantly female (62%), and presented with severe baseline pain (mean VAS 7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4) and substantial functional disability (mean ODI 66.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of Study Participants by Treatment Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFemale, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePain Duration (weeks)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSessions Attended\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBaseline Pain VAS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBaseline ODI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e44.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e80 (63.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e27.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExercise Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e46.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e101 (61.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e66.2\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eManual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e46.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or n (%). VAS\u0026thinsp;=\u0026thinsp;Visual Analog Scale; ODI\u0026thinsp;=\u0026thinsp;Oswestry Disability Index. No significant differences between groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all comparisons).\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003e4.2. Primary Treatment Outcomes\u003c/h2\u003e\u003cp\u003eAll three treatment groups showed significant improvement in pain (VAS) and disability (ODI) from before to after treatment (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The greatest improvements were in the combined therapy group, followed by exercise therapy. Manual therapy showed the smallest improvements.\u003c/p\u003e\u003cp\u003eOn average, patients in the combined therapy group achieved a 5.0-point reduction in VAS and a 15.9-point reduction in ODI, compared with 4.0 and 12.4 points in the exercise therapy group and 2.3 and 6.0 points in the manual therapy group, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Between-group comparisons confirmed that combined therapy was significantly more effective than both exercise therapy and manual therapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 for all). Exercise therapy also outperformed manual therapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePrimary Treatment Outcomes by Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePain VAS Baseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePain VAS Post-treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePain VAS Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eODI Baseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eODI Post-treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eODI Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eMeaningful Improvement%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e48.7\u0026thinsp;\u0026plusmn;\u0026thinsp;24.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e-15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e78.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExercise Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e66.2\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e53.8\u0026thinsp;\u0026plusmn;\u0026thinsp;23.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e-12.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e55.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eManual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e64.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e-6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. VAS\u0026thinsp;=\u0026thinsp;Visual Analog Scale (0\u0026ndash;10); ODI\u0026thinsp;=\u0026thinsp;Oswestry Disability Index (0-100). Negative change scores indicate improvement. All within-group changes were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEffect size analysis further supported these findings (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The combined therapy group showed large effects compared with manual therapy for both pain (d\u0026thinsp;=\u0026thinsp;1.67) and disability (d\u0026thinsp;=\u0026thinsp;1.23). Exercise therapy also produced large effects versus manual therapy (d\u0026thinsp;=\u0026thinsp;1.14 for pain, d\u0026thinsp;=\u0026thinsp;0.77 for disability). The comparison between combined and exercise therapy yielded medium effects for pain (d\u0026thinsp;=\u0026thinsp;0.59) and small-to-medium effects for disability (d\u0026thinsp;=\u0026thinsp;0.42).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eClinically meaningful improvements (\u0026ge;\u0026thinsp;2 points for VAS AND\u0026thinsp;\u0026ge;\u0026thinsp;10 points for ODI) were achieved in 78% of patients receiving combined therapy, 55% of those receiving exercise therapy, and 0% of those receiving manual therapy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo strengthen the clinical interpretation of the findings, the relative treatment effects were further expressed in absolute measures, applying a conservative definition that required both a clinically meaningful reduction in pain (\u0026ge;\u0026thinsp;2 points on the VAS) and a functional improvement of at least 10 points on the ODI. Under this criterion, combined therapy demonstrated an absolute risk difference of 22.5 percentage points when compared with exercise therapy (78.0% vs. 55.5%; 95% CI: 11.9 to 33.1), which translates into a number needed to treat (NNT) of 4. This indicates that for every four patients managed with combined therapy rather than exercise therapy alone, one additional patient is expected to achieve meaningful gains in both pain relief and functional status.\u003c/p\u003e\u003cp\u003eThe benefit of combined therapy over manual therapy was very large, with an absolute risk difference of 78.0 percentage points (78.0% vs. 0.0%; 95% CI: 70.3 to 85.7). This gave a number needed to treat (NNT) of 1. Exercise therapy was also better than manual therapy, with an absolute risk difference of 55.5 percentage points (55.5% vs. 0.0%; 95% CI: 47.4 to 63.6) and an NNT of 2. More details can be found in Table S5 of the Supplementary Materials.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e\u003ch2\u003e4.3 Multivariable and Sensitivity Analysis\u003c/h2\u003e\u003cp\u003eThe baseline characteristics were similar across all treatment groups, with no significant differences between them (Table S3, Supplementary). Multivariable linear regression models were used, adjusting for age, gender, BMI, baseline VAS, and baseline ODI. The results confirmed the primary findings. The adjusted treatment effects stayed statistically significant and clinically meaningful, with less than 0.15 points difference from the unadjusted values. The model explained 16.6% of the variance in VAS pain change scores (R\u0026sup2; = 0.166), showing that confounding factors had minimal impact (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnadjusted vs. Confounder-Adjusted Treatment Effects for VAS Pain Change\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComparison\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnadjusted Estimate (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAdjusted Estimate (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eChange\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined vs Exercise Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;0.97 (\u0026minus;\u0026thinsp;1.33 to \u0026minus;\u0026thinsp;0.60)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;0.83 (\u0026minus;\u0026thinsp;1.18 to \u0026minus;\u0026thinsp;0.48)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e+\u0026thinsp;0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined vs Manual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;2.68 (\u0026minus;\u0026thinsp;3.52 to \u0026minus;\u0026thinsp;1.84)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;2.64 (\u0026minus;\u0026thinsp;3.48 to \u0026minus;\u0026thinsp;1.80)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e+\u0026thinsp;0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExercise vs Manual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;1.72 (\u0026minus;\u0026thinsp;2.55 to \u0026minus;\u0026thinsp;0.88)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;1.81 (\u0026minus;\u0026thinsp;2.64 to \u0026minus;\u0026thinsp;0.98)***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026minus;0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are mean differences in VAS pain change scores. Negative values indicate greater improvement in the first group listed. Adjusted estimates are controlled for age, sex, BMI, baseline VAS, and baseline ODI. **\u003c/em\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e\u003cp\u003eThe sensitivity analyses used multiple imputation, per-protocol, and last-observation-carried-forward methods. The results were almost the same in all cases, showing that the findings were strong even with different ways of handling missing data (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSensitivity Analysis of Treatment Effects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnalysis Method\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCombined vs Exercise (VAS)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCombined vs Manual (VAS)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete Case (Primary)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.9 (-1.3 to -0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.7 (-3.5 to -1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWorst Case Scenario\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.9 (-1.3 to -0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.7 (-3.5 to -1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBest Case Scenario\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.9 (-1.3 to -0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.7 (-3.5 to -1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLOCF Analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.9 (-1.3 to -0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.7 (-3.5 to -1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues represent mean differences (95% confidence intervals). Negative values indicate greater improvement in the first group mentioned. ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all comparisons.\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e\u003ch2\u003e4.4. Secondary Outcomes\u003c/h2\u003e\u003cp\u003eMedication use decreased substantially in all groups, with the greatest reductions observed in the combined therapy group. NSAID use declined by 72.5% and opioid use by 97% in the combined therapy group, compared with smaller reductions in the exercise and manual therapy groups. Combined therapy also demonstrated the lowest recurrence rate of low back pain during follow-up (4.7% vs. 10.4% for exercise therapy and 18.2% for manual therapy; Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSecondary Outcomes by Treatment Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNSAIDs Before\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNSAIDs After\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOpioids Before\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOpioids After\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePain Recurrence\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eFollow-up Median (IQR)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e89/127 (70.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e35/127 (27.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e36/127 (28.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1/127 (0.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e6/127 (4.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.9 (2.9\u0026ndash;6.4) months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExercise Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e123/164 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e39/164 (23.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e43/164 (26.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0/164 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e17/164 (10.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.9 (2.7\u0026ndash;6.2) months*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eManual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9/11 (81.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4/11 (36.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4/11 (36.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0/11 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2/11 (18.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.7 (1.6-5.0) months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are presented as n (%) or median (IQR). NSAIDs\u0026thinsp;=\u0026thinsp;non-steroidal anti-inflammatory drugs. Combination medications were recoded into the predominant drug class for consistency. Exercise therapy group includes one extreme outlier (655.5 months). *\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median follow-up duration was 8.3 months (IQR 6.5\u0026ndash;10.2), which was comparable across treatment groups. Missingness for secondary outcomes was minimal and did not differ by group, supporting the validity of these results (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003e4.5 Subgroup Analyses\u003c/h2\u003e\u003cp\u003eSubgroup analyses showed that baseline pain severity and BMI significantly modified treatment outcomes. Patients with severe baseline pain achieved greater improvements in both VAS and ODI scores than those with moderate pain (p\u0026thinsp;=\u0026thinsp;0.008; Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;6).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePain Category Analysis by Treatment Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModerate Pain n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSevere Pain n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eModerate Pain Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eModerate ODI Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSevere Pain Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSevere ODI Change\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33/127 (26.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e94/127 (74.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-18.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-15.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExercise Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43/164 (26.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e121/164 (73.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-15.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-11.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eManual Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1/11 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10/11 (90.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-6.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are presented as n (%) or mean change scores. Negative values indicate improvement.\u003c/em\u003e\u003c/p\u003e\u003cp\u003eSimilarly, patients with BMI\u0026thinsp;\u0026lt;\u0026thinsp;30 demonstrated greater functional gains compared with obese patients, particularly for ODI improvement (p\u0026thinsp;=\u0026thinsp;0.003; Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment Effectiveness by BMI Category\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI Category\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOverall Pain Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOverall ODI Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBest Treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBest Pain Improvement\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTreatment Ranking\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e-15.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.4 points\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCT: 4.4\u0026thinsp;\u0026gt;\u0026thinsp;ET: 4.3\u0026thinsp;\u0026gt;\u0026thinsp;MT: 1.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e-14.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.3 points\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCT: 5.3\u0026thinsp;\u0026gt;\u0026thinsp;ET: 3.9\u0026thinsp;\u0026gt;\u0026thinsp;MT: 2.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e-11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCombined Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.8 points\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCT: 4.8\u0026thinsp;\u0026gt;\u0026thinsp;ET: 3.9\u0026thinsp;\u0026gt;\u0026thinsp;MT: 2.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eValues are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. CT\u0026thinsp;=\u0026thinsp;Combined Therapy; ET\u0026thinsp;=\u0026thinsp;Exercise Therapy; MT\u0026thinsp;=\u0026thinsp;Manual Therapy. Negative values indicate improvement.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn contrast, treatment effects were consistent across age groups and gender, with no statistically significant interaction effects (p\u0026thinsp;=\u0026thinsp;0.080 and p\u0026thinsp;=\u0026thinsp;0.454, respectively; Table S4, Supplementary; Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eThis study gives strong real-world evidence that combining manual therapy with exercise therapy is superior to either modality alone for chronic low back pain (CLBP). The results confirm that combined care improves both pain and function reflecting the advantage of a multimodal approach, including reduced medication reliance and lower recurrence rates. These findings strongly support the use of combined therapy in clinical practice and help fill important gaps in the current evidence.\u003c/p\u003e\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\u003ch2\u003e5.1. Primary Outcomes and Clinical Significance\u003c/h2\u003e\u003cp\u003eThe primary result of this study confirmed that combined therapy produce meaningful improvements in both pain and disability, demonstrated reduction in Pain by 5.0 points on the VAS, and improvement in disability by 15.9 points on the ODI. These changes were much greater than the established MCID thresholds [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. This provides strong real-world support for recent high-quality studies. For example, the review by Narenthiran and others [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] showed that 8 out of 10 studies found benefits when manual therapy was added to exercise. Our results strongly confirm this. The size of improvement in our combined therapy group (78% achieving meaningful improvement in both pain and disability) was almost the same as the trial by Blanco-Gim\u0026eacute;nez and others [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], which showed 87.7% improvement with combined therapy compared to 27.1% with exercise alone.\u003c/p\u003e\u003cp\u003eThe effect sizes for combined therapy compared to manual therapy alone were very large (d\u0026thinsp;=\u0026thinsp;1.67 for pain, d\u0026thinsp;=\u0026thinsp;1.23 for disability). Based on Cohen\u0026rsquo;s guidelines [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], these values are in the \u0026ldquo;large\u0026rdquo; range. This means the differences are clinically important and bring great improvements in patients\u0026rsquo; quality of life. In most studies, treatments usually give only small or moderate improvements in pain and disability [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Our results show that combining manual and exercise therapy can create stronger effects in real-world practice.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\u003ch2\u003e5.2. Mechanisms of Action\u003c/h2\u003e\u003cp\u003eThe superior results in the exercise therapy and combined therapy groups may be due to the different ways manual therapy and exercise therapy work. Manual therapy methods, such as mobilization and manipulation, are thought to give short-term pain relief [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Those techniques affecting pain through mechanical and nerve pathways and by improving movement in the spine, which helps patients return to activity sooner.\u003c/p\u003e\u003cp\u003eIn contrast, exercise therapy gives longer-lasting improvement. It works by reducing deconditioning, improving motor control, and addressing psychosocial factors related to long-term pain. Systematic Reviews have shown that the benefits of exercise continue even after treatment ends, with steady improvements in pain and function in the short, intermediate, and long term [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTogether, these effects suggest that manual therapy and exercise work best when combined. Manual therapy helps by giving quick pain relief and better movement, which makes it easier for patients to take part in exercise. Exercise then builds on this progress and keeps the recovery going. This teamwork between the two approaches likely explains why combined therapy gives better results than using only one treatment [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\u003ch2\u003e5.3. Secondary Outcomes: Comprehensive Treatment Benefits\u003c/h2\u003e\u003cdiv id=\"Sec32\" class=\"Section3\"\u003e\u003ch2\u003e5.3.1. Medication Reduction\u003c/h2\u003e\u003cp\u003eAn important result of this study is that combined therapy reduced the need for medicine more than single treatments. NSAID use reduced by 72.5% and opioid use by 97.2%. These reductions were much greater than those seen with either therapy alone. The reduction in opioid use is very large, but it should be read with ccautious because the number of opioid users in each group was small. The reduction in NSAID use was seen in larger groups, so it is more reliable and likely to be clinically important.\u003c/p\u003e\u003cp\u003eThese results align with other studies showing that non-drug treatments can lower the need for medicine. For example, early physical therapy has been linked to less opioid and non-opioid use at discharge [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Manual therapy has also been linked to less tramadol use over one year in adults with new low back pain [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In another trial, aerobic exercise gave pain relief similar to morphine before treatment [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The medication reduction in our study also matches the findings of Gedin and others [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], who found that combined therapy gave lower direct healthcare costs and the best QALY gains compared with single treatments. Their study did not look at medication use directly, but the lower costs may partly be due to less need for medicine as well as fewer other healthcare costs.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec33\" class=\"Section3\"\u003e\u003ch2\u003e5.3.2. Pain Recurrence Prevention\u003c/h2\u003e\u003cp\u003eA key result in our study is the significant lower pain recurrence with combined therapy (4.7%) compared with exercise therapy (10.4%) and manual therapy (18.2%). This is an important long-term outcome. Recurrent low back pain is linked to greater disability, longer absence from work, and greater healthcare and social costs [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In general, low back pain is one of the main causes of limited activity and economic burden worldwide [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur results on recurrence rate with evidence that exercise can reduce relapse risk. A Cochrane review summarized by Roren and others [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e] reported around a 50% reduction in 1-year recurrence compared with no treatment. Still, results in the wider literature are mixed. The TOPS trial found that exercise plus education did not reduce recurrence compared with an education booklet [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Koumantakis and others [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] also reported no added benefit when stabilization was added to general exercise for recurrent low back pain, although subgroup analyses suggested possible reductions. Despite these mixed results, the very low recurrence in our combined therapy group suggests that structured multimodal care may offer an advantage.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec34\" class=\"Section2\"\u003e\u003ch2\u003e5.4. Subgroup Analysis: Personalized Treatment Insights\u003c/h2\u003e\u003cp\u003eOur subgroup analysis showed that all patients improved, but some groups had larger benefits. The biggest differences were seen in baseline pain severity and body mass index. Patients with severe pain at baseline gained significantly greater than those with moderate pain (p\u0026thinsp;=\u0026thinsp;0.008). This suggests that intensive multimodal approach may be most useful for severe cases. These results differ from earlier studies, which found that milder cases often improved more [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In terms of BMI, overweight patients (25\u0026ndash;29.9) had the best disability improvement, while obese patients (\u0026ge;\u0026thinsp;30) showed smaller gains. This supports earlier evidence that obesity can limit physiotherapy outcomes [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn contrast, age and gender had little effect. Younger patients showed slightly better results, likely due to better healing and fewer comorbidities [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. However, these differences were not statistically significant. Both men and women improved in a similar way with combined therapy. This aligns with previous systematic reviews and guidelines, which found no important gender differences in low back pain outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThese results suggest that baseline severity and BMI are the most important factors that change how patients respond to treatment. Age and gender seem to have little effect. Rehabilitation plans that focus on these patient factors, especially extra support for obese patients, may help improve outcomes in chronic low back pain.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec35\" class=\"Section2\"\u003e\u003ch2\u003e5.5. Comparison with Previous Research and Clinical Guidelines\u003c/h2\u003e\u003cp\u003eOur results support and extend the current evidence for multimodal approaches in chronic low back pain. The systematic review by Gonz\u0026aacute;lez-G\u0026oacute;mez and others [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] showed no clear difference between manual therapy and exercise therapy when used alone. In contrast, our study showed that combined therapy was clearly better than either single treatment. This provides real-world support for clinical practice guidelines, such as those from the American College of Physicians, which now recommend multimodal care for chronic low back pain.\u003c/p\u003e\u003cp\u003eMoreover, our results contrasted the earlier study by Hsieh and others [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], that showed no benefit of combined therapy compared to single treatments in patients with subacute pain. The difference may be because our study focused on chronic patients, had a larger sample size, and used real-world clinical data that reflects normal practice.\u003c/p\u003e\u003cp\u003eAlthough, our study focused only on physical treatments, current guidelines [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] also highlight the importance of psychological care, such as cognitive behavioural therapy (CBT). Evidence shows that CBT gives small but steady benefits in lowering pain, disability, and emotional distress in people with chronic pain [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Our results show that physical multimodal approaches effective, but future studies should test if adding psychological care to combined therapy can give even better results.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec36\" class=\"Section2\"\u003e\u003ch2\u003e5.6. Clinical Implications and Implementation\u003c/h2\u003e\u003cdiv id=\"Sec37\" class=\"Section3\"\u003e\u003ch2\u003e5.6.1. Robust Statistical Analysis and Confounding Control\u003c/h2\u003e\u003cp\u003eOne strength of this study is that the treatment groups were balanced, with no significant differences in age, gender, BMI, or pain scores (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). This balance makes the results more reliable because it reduces the chance of bias. In addition, when we used regression analysis to adjust for possible confounders, the results were almost the same as the unadjusted results, with less than 0.15 points difference on the VAS scale. This shows that the findings are strong and not likely to change because of hidden factors. Giving both adjusted and unadjusted results also increases clarity and follows the STROBE guidelines for observational studies.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec38\" class=\"Section3\"\u003e\u003ch2\u003e5.6.1. Treatment Protocol Development\u003c/h2\u003e\u003cp\u003eThe strong results of combined therapy in different outcomes domains supports the development of standardized multimodal treatment protocols for chronic low back pain. These protocols should include both manual therapy and structured exercise programs. The level and length of treatment can then be adjusted depending on the baseline of pain severity at the start.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec39\" class=\"Section3\"\u003e\u003ch2\u003e5.6.2. Healthcare Resource Allocation\u003c/h2\u003e\u003cp\u003eThe cost-effectiveness of our results is important. While Combined therapy may need more resources, the superior outcomes in pain reduction, functional improvement, medication reduction, and recurrence prevention likely result in overall healthcare cost savings through reduced long-term healthcare utilization. This aligns with trial evidence showing that combination therapy offers superior cost-effectiveness compared with exercise or manual therapy alone [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and with epidemiological data showing low back pain creates a high economic burden on healthcare systems worldwide [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec40\" class=\"Section3\"\u003e\u003ch2\u003e5.6.3. Patient Education and Expectations\u003c/h2\u003e\u003cp\u003eThe wide benefits of combined therapy, such as reducing medication use and lowering recurrence rate, are important points for patient education. Patients can be advised that using more than one type of treatment not only gives better pain relief but also helps them depend less on medicine and avoid future episodes. From a clinical counseling perspective, patients can also be informed that combined therapy provides approximately a 72% chance of achieving meaningful improvement in both pain and function, compared with about 50% with exercise therapy alone. For clinicians, this translates to treating four patients with combined therapy instead of exercise therapy alone to achieve one additional successful outcome (NNT\u0026thinsp;=\u0026thinsp;4).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec41\" class=\"Section2\"\u003e\u003ch2\u003e5.7. Limitations and Statistical Considerations\u003c/h2\u003e\u003cp\u003eSeveral limitations should be considered when interpreting these results:\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConfounding and Causal Inference\u003c/strong\u003e\u003cp\u003eThis study used a retrospective design, which may allow unmeasured confounding to affect the results. Still, several factors strengthen causal inference in this study. First, the treatment groups baseline were balanced in all measured characteristics (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), suggesting minimal confounding by indication. Second, while carrying out multivariable adjustment for key confounders such as age, gender, BMI, and baseline scores, the results stayed almost the same as the unadjusted ones (less than 0.15 VAS points difference). This shows that the measured confounders did not bias the results. However, other unmeasured confounders like patient motivation, therapist skill, or treatment attendance may still play a role and limit how strong the conclusions are.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical Power and Manual Therapy Group Size\u003c/strong\u003e\u003cp\u003eOne important limitation of this study is the very small size of the manual therapy group (n\u0026thinsp;=\u0026thinsp;11). This makes it difficult to detect real differences and increases the chance of error. Under the conservative definition of clinically meaningful improvement (\u0026ge;\u0026thinsp;2-point VAS and \u0026ge;\u0026thinsp;10-point ODI), none of the manual therapy patients achieved both thresholds. This striking result should be interpreted with caution, as the group was underpowered (post-hoc power\u0026thinsp;~\u0026thinsp;30%) and may underestimate the true potential benefit of manual therapy. This means that the large effect size differences observed between manual therapy and the other groups could be overstated because of the small number of patients. Future studies should include at least 30 patients in each group to reach proper power (80%) and allow stronger comparisons.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMissing Data and Robustness of Findings\u003c/strong\u003e\u003cp\u003eA strength of this study is that outcome data were almost complete, with only 1.3% missing VAS scores and 2.0% missing ODI scores. Comprehensive sensitivity analyses using different assumptions for missing data (worst-case scenario, best-case scenario, and last observation carried forward) gave the same results as the main analysis. This shows that the results are robust and do not depend on missing data handling assumptions. The very small amount of missing data also lowers the chance of bias from differential dropout patterns across treatment groups.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eGeneralizability (External Validity)\u003c/strong\u003e\u003cp\u003eThe results of this study are likely generalizable to adult patients with non-specific chronic low back pain who are treated on similar tertiary care hospitals. This is most relevant for patients with similar demographics, such as a mean age of about 46 years and with 62% being female, and who have access to both manual and exercise therapy. However, there are some factors that may reduce how much the results can be applied to other settings.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e(1) Healthcare Setting - Results may be different in primary care, where treatment methods, therapist skills, and patient selection are not the same; (2) Geographic and Cultural Factors - This study was done in a Middle Eastern hospital, so cultural views on pain and treatment may affect outcomes in other regions; (3) Treatment Standardization- The specific manual therapy and exercise protocols used may not be universally available across different healthcare systems; (4) Patient Selection- The study included patients who completed at least four treatment sessions, potentially representing a more motivated population compared to typical clinical practice; (5) Healthcare Resources - In places with limited resources, it may be difficult to provide combined therapy.\u003c/p\u003e\u003cp\u003eHealthcare providers should consider local patient characteristics, available resources, and treatment protocols when applying these findings. Future multi-center studies across diverse healthcare settings would strengthen the evidence base for generalizability.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFollow-up Duration Variability\u003c/strong\u003e\u003cp\u003eAnother limitation of this study is the presence of extreme outliers in follow-up duration. For example, one patient had a follow-up period of 655.5 months. Although this did not change the median follow-up time, it shows the challenges of using retrospective data. This problem highlights the need for future prospective studies with standardized follow-up protocols. In addition, while many secondary outcomes were analyzed, some important measures such as return to work, healthcare use, and patient satisfaction were not available in the electronic health records. Including these outcomes in future studies would provide a more complete view of treatment effectiveness.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec42\" class=\"Section2\"\u003e\u003ch2\u003e5.8. Future Research Directions\u003c/h2\u003e\u003cp\u003eBased on our results, there are several important directions for future research. First, large randomized controlled trials are needed to confirm these findings and to define the best treatment protocols for combined therapy. Second, studies with longer follow-up should be done to test if the benefits last over time and to find which factors are linked with sustained improvement.\u003c/p\u003e\u003cp\u003eThird, future studies should test the optimal sequencing and timing of manual therapy and exercise components within combined programs. In addition, prospective studies should incorporate detailed recording of treatment intensity and session spacing, as the distribution of sessions (for example, concentrated within a few weeks versus spread over several months) may influence effectiveness.Fourth, research should also include economic studies to check if combined therapy is cost-effective in different healthcare systems and populations.\u003c/p\u003e\u003cp\u003eFinally, future studies should explore the mechanisms underlying the superior effectiveness of combined therapy. This includes examining the role of neurophysiological, biomechanical, and psychological factors that may explain the success of this approach.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec43\" class=\"Section2\"\u003e\u003ch2\u003e5.9. Conclusion\u003c/h2\u003e\u003cp\u003eThis study shows that using manual therapy and exercise therapy together works better than using each treatment alone for chronic low back pain. The combined approach not only reduced pain and improved function but also lowered the need for medication, reduced recurrence, and worked well in different patient groups. These benefits are likely because manual therapy helps with short-term pain relief, while exercise therapy gives longer-lasting functional improvement.\u003c/p\u003e\u003cp\u003eThe large effects seen, especially when comparing combined therapy with manual therapy alone, show clinically significant improvements in patient outcomes. The reductions in medication use and recurrence also suggest that this approach may save healthcare costs and guide future clinical recommendations. However, these findings should be viewed with caution because of the retrospective design, single-center setting, and the small sample size in the manual therapy group. Even with these limits, the study strongly supports combined therapy as a first-line option for chronic low back pain. Future studies should examine these results in large randomized controlled trials, consider the optimal sequencing of manual and exercise interventions, and explore mechanisms underlying treatment success across diverse populations.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e \u003cstrong\u003eYazeed Timraz\u003c/strong\u003e and Ali Sahari\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e \u003cstrong\u003eYazeed Timraz\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003eFaisal Alotaibi\u003c/strong\u003e,\u003c/strong\u003e and Shouq Almutairi\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Curation:\u003c/strong\u003e Ali Sahari, \u003cstrong\u003eFaisal Alotaibi\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e Shouq Almutairi, \u003cstrong\u003eAhmed Hammami\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003eAmal Alsaad\u003c/strong\u003e, \u003cstrong\u003eFay Almehrej\u003c/strong\u003e, \u003cstrong\u003eMayyer Alanazi\u003c/strong\u003e, \u003cstrong\u003eReem Aldosary\u003c/strong\u003e, \u003cstrong\u003eThikra Alotaibi\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFormal analysis:\u003c/strong\u003e \u003cstrong\u003eYazeed Timraz\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eRahaf Bin Salamah\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSoftware: Yazeed Timraz\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eValidation:\u003c/strong\u003e \u003cstrong\u003eAhmed Hammami\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eAmal Alsaad\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigation:\u003c/strong\u003e \u003cstrong\u003eAli Sahari\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003eFaisal Alotaibi,\u003c/strong\u003e \u003cstrong\u003eShouq Almutairi\u003c/strong\u003e, \u003cstrong\u003eAhmed Hammami\u003c/strong\u003e, \u003cstrong\u003eAmal Alsaad\u003c/strong\u003e, \u003cstrong\u003eFay Almehrej,\u003c/strong\u003e \u003cstrong\u003eMayyer Alanazi\u003c/strong\u003e, \u003cstrong\u003eReem Aldosary\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eThikra Alotaibi\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting\u0026mdash;original draft preparation: \u003cstrong\u003eYazeed Timraz\u003c/strong\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting\u0026mdash;review and editing:\u003c/strong\u003e \u003cstrong\u003eYazeed Timraz\u003c/strong\u003e, Ali Sahari, \u003cstrong\u003eFaisal Alotaibi\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e and \u003cstrong\u003eHomoud Rajab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisualization:\u003cstrong\u003eFay Almehrej\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupervision:\u003c/strong\u003e \u003cstrong\u003eYazeed Timraz\u003c/strong\u003e and \u003cstrong\u003eHomoud Rajab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProject administration:\u003c/strong\u003e Yazeed Timraz\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResources:\u003c/strong\u003e \u003cstrong\u003eHomoud Rajab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study received no external funding. The research was conducted as part of institutional academic activities. The sponsor had no role in study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u003c/strong\u003e Human Ethics and Consent to Participate declarations: The study protocol was approved by the Institutional Review Board of King Abdullah International Medical Research Center (IRB #00000169625). The IRB granted a waiver of individual informed consent due to the retrospective, de-identified nature of the data. All procedures were conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable. Individual consent was waived by the IRB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable. This was a retrospective cohort study and not a clinical trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable. This study was not prospectively registered as a clinical trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e The anonymized dataset was made available to editors and reviewers during peer review. It is not publicly archived but may be obtained from the corresponding author upon reasonable request and with appropriate ethical approval.\u003c/p\u003e\n\u003cp\u003eAcknowledgments:\u0026nbsp;The authors thank the rehabilitation therapists who generously contributed their time and expertise. We are also grateful to the Rehabilitation Department at the Ministry of National Guard\u0026ndash;Health Affairs for facilitating data collection and access to clinical areas.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest, financial or non-financial.\u003c/p\u003e\n\u003cp\u003eAI Declaration: AI tools, such as ChatGPT, were used only to edit language and paraphrase text to make it clearer and grammatically correct. The design of the study, data collection, analysis, and interpretation were all completed fully by the authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAwaji, M. A. Epidemiology of low back pain in Saudi Arabia. \u003cem\u003eJ. Adv. Med. Pharm. 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Psychological therapies for the management of chronic pain (excluding headache) in adults. \u003cem\u003eCochrane Database Syst. Rev.\u003c/em\u003e \u003cb\u003e2020\u003c/b\u003e (8), CD007407. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD007407.pub4\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD007407.pub4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chronic low back pain, Manual therapy, Exercise therapy, Combined therapy, Retrospective cohort, Pain management, Functional disability, Medication use, Recurrence, Body mass index","lastPublishedDoi":"10.21203/rs.3.rs-7720973/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7720973/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe best conservative treatment for chronic low back pain (CLBP) remains uncertain. This study aimed to evaluate the effectiveness of manual therapy (MT), exercise therapy (ET), and their combination (MT\u0026thinsp;+\u0026thinsp;ET) in real-world clinical practice. Secondary outcomes and subgroup analyses were also included.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective cohort study was conducted on 302 patients with chronic low back pain (CLBP) treated at the Rehabilitation Department of the National Guard Hospital in Riyadh, Saudi Arabia, between 2023 and 2024. The patients were divided into three groups: manual therapy (MT), exercise therapy (ET), and a combination of both (MT\u0026thinsp;+\u0026thinsp;ET). The main outcomes were pain intensity, measured with the Visual Analog Scale (VAS), and functional disability, assessed with the Oswestry Disability Index (ODI). Secondary outcomes included medication use, recurrence of pain, and follow-up duration. Subgroup analyses examined treatment effects according to age, gender, baseline pain severity, and body mass index (BMI).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAll three groups showed significant improvement in both pain and disability (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The combined therapy group achieved the greatest reductions in pain (mean change \u0026minus;\u0026thinsp;5.0) and disability (mean change \u0026minus;\u0026thinsp;15.9), compared to ET (pain \u0026minus;\u0026thinsp;4.0, disability \u0026minus;\u0026thinsp;12.4) and MT (pain \u0026minus;\u0026thinsp;2.3, disability \u0026minus;\u0026thinsp;6.0) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all). The combined therapy group achieved clinically meaningful improvement in 78% of patients compared to 55.5% for exercise therapy and 0% for manual therapy. Combined therapy showed superior medication reduction (72.5% NSAIDs reduction vs 51.2% ET vs 45.5% MT) and lowest recurrence rates (4.7% vs 10.4% vs 18.2%). Patients with severe baseline pain showed significantly greater improvement than those with moderate pain (p\u0026thinsp;=\u0026thinsp;0.008). BMI analysis revealed that overweight patients showed the greatest response to combined therapy (5.3 points pain reduction), while obese patients had significantly reduced functional improvement (p\u0026thinsp;=\u0026thinsp;0.003).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe combination of manual therapy and exercise therapy is more effective than either treatment alone for reducing pain, improving function, lowering medication use, and preventing recurrence in patients with chronic low back pain. The findings also show that treatment outcomes vary according to baseline pain severity and body mass index (BMI). Overweight patients had the best response to combined therapy, which suggests that treatment should be adjusted based on patient characteristics.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e\u003cp\u003eNot applicable. This study was not prospectively registered as a clinical trial.\u003c/p\u003e","manuscriptTitle":"Comparative Effectiveness of Manual Therapy, Exercise Therapy, and Combined Therapy for Chronic Low Back Pain: A Comprehensive Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 07:16:51","doi":"10.21203/rs.3.rs-7720973/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4590a611-a906-4678-b9db-b13d8f0aa0d8","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57399218,"name":"Health sciences/Diseases"},{"id":57399219,"name":"Health sciences/Health care"},{"id":57399220,"name":"Health sciences/Medical research"},{"id":57399221,"name":"Health sciences/Signs and symptoms"}],"tags":[],"updatedAt":"2026-01-18T21:53:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-14 07:16:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7720973","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7720973","identity":"rs-7720973","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}