What is the Optimal Timing to Assess the Effect of 5-ASA in Patients with Mild-to- Moderate Ulcerative Colitis? A Single-Center Prospective Observational Study

What is the Optimal Timing to Assess the Effect of 5-ASA in Patients with Mild-to- Moderate Ulcerative Colitis? 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A Single-Center Prospective Observational Study Yu Da, Fang Wang, Jiaqi Zhang, Tiantian Zhang, Xiaoning Liu, Jindan He, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7873738/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background First-line therapy for mild-to-moderate ulcerative colitis is 5-aminosalicylic acid. Optimal timing for the first evaluation after initiation remains unclear. Early follow-up may not reflect efficacy, while delayed assessment could be inefficient. We conducted a prospective observational cohort study to identify the optimal evaluation time after 5-aminosalicylic acid induction in newly diagnosed patients. Methods The cohort included 157 patients at Xijing Hospital. All received standard 5-aminosalicylic acid therapy, grouped by first follow-up timing: 4 weeks (W4; N = 41), 8 weeks (W8; N = 40), or 12 weeks (W12; N = 42). Dose adjustments followed physician assessment. Primary outcome was clinical response/remission rate at Week 12 (Partial Mayo score). Secondary outcomes included inflammatory markers, mucosal healing, and dose adjustments. Results At Week 4, 68.29% of the W4 group achieved early clinical response. 82.93% in the W4 group reduced 5-aminosalicylic acid dosage by Week 4, versus 67.50% in the W8 group by Week 8. Consequently, cumulative 5-ASA exposure was lower in the W4 group. At Week 12, remission rates were similarly high across groups. At 24 weeks, long-term outcomes were comparable. Conclusion Follow-up at 4 weeks enables timely dose optimization and reduced healthcare costs without compromising 6-month efficacy. Thus, 4 weeks may be optimal for first evaluation after starting 5-ASA in mild-to-moderate ulcerative colitis. Trial Registration This trial was retrospectively registered on ClinicalTrials.gov (NCT06998693) on May 6, 2025. Ulcerative colitis 5-aminosalicylic acid Follow-up timing Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon that imposes a substantial global health burden[ 1 ]. In 2023, the worldwide prevalence of UC was estimated at roughly 5 million cases[ 1 ], and sustained growth in UC prevalence persists globally across all epidemiological stages[ 2 ]. Typical clinical manifestations of UC include abdominal pain, diarrhea, mucopurulent bloody stools, and tenesmus; some patients also exhibit systemic symptoms such as fatigue, weight loss, and extraintestinal manifestations[ 3 ]. Even mild-to-moderate UC can significantly impair quality of life[ 4 ]. Ongoing inflammation also carries long-term risks, as repeated disease flares can cause physical and psychological harm and lead to cumulative bowel damage[ 5 ]. These epidemiological and clinical realities underscore the pressing need for optimized management strategies in UC. Contemporary practice guidelines recommend combined systemic and topical 5-aminosalicylic acid (5-ASA) as the first-line induction therapy for mild-to-moderate UC[ 5 , 6 ]. However, an evidence-based standard for the assessment timing of UC patients receiving 5-ASA has not been firmly established. In current clinical practice, follow-up intervals after initiating 5-ASA vary widely. Some clinicians schedule the first evaluation for patients with mild disease at 8–12 weeks. However, delaying efficacy assessment for two to three months may result in prolonged uncontrolled mucosal inflammation in suboptimal responders. In contrast, good responders incur unnecessary medication costs through sustained high-dose therapy. With the emergence of the “treat-to-target” concept, there is increasing recognition that earlier identification of inadequate responders allows clinicians to intervene sooner[ 7 ]. However, it remains unclear how soon is sufficiently early to balance giving 5-ASA adequate time to act versus avoiding undue delay in non-responders. A randomized controlled trial (RCT) indicated that clinical remission rates after 5-ASA treatment were 18%–25% at three weeks, increasing markedly to 35%–43% at six weeks[ 8 ]. Therefore, the American Gastroenterological Association consensus recommends assessing symptom improvement at 4–8 weeks of 5-ASA therapy to guide further medication decisions[ 9 ]. The American College of Gastroenterology Clinical Guidelines issued a key concept statement that patients with mildly to moderately active ulcerative colitis should be reassessed within 8 weeks to determine their response to induction therapy[ 6 ]. In the pharmacodynamic data (ASCEND II trial), the median time to cease rectal bleeding was nine days in patients receiving 4.8 g/d 5-ASA, and 16 days in patients receiving 2.4 g/d[ 10 ]. The finding suggests that the onset window for therapeutic action of 5-ASA is relatively short; clinical benefit generally emerges within 2–4 weeks after treatment initiation[ 11 ]. Another RCT demonstrated that among patients without improvement in rectal bleeding or stool frequency after 14 days of adequate 5-ASA treatment, 56% and 75%, respectively, continued to show no improvement after six weeks[ 12 ]. In contrast, 74%–86% of patients achieving clinical remission by day 14 maintained remission subsequently. These findings support the concept that early assessment of 5-ASA efficacy in moderately active UC can inform therapeutic decision-making. Based on this evidence, the European Crohn's and Colitis Organization (ECCO) suggests escalation therapy in UC patients without symptom improvement after 10–14 days of treatment[ 13 ]. However, Orchard et al. found that while 10–14 days of therapy may suffice for symptomatic improvement, rectal bleeding and abnormal stool frequency resolution requires 19–29 days[ 12 ]. This raises concern that efficacy assessment at 10–14 days might be premature for mild-to-moderate UC patients, potentially leading to inappropriate step-down therapy. Moreover, a randomized controlled trial demonstrated a continued rapid increase in clinical remission rates between weeks 2–4 post-treatment, with this upward trend plateauing only after week 4[ 14 , 15 ]. These findings further indicate that evaluation at 2 weeks risks misclassifying 5-ASA-responsive patients as suboptimal responders. This conflict creates a clinical challenge: identify a "sweet spot" between allowing adequate drug response time, avoiding prolonged ineffective therapy in non-responders, and preventing premature de-escalation in responders. To resolve this, we conducted a single-center prospective observational cohort study to compare three evidence-based assessment timepoints to assess the impact of different initial assessment timing on 5-ASA treatment response in newly diagnosed UC patients. Materials and Methods Trial design This study was designed as a single-center, prospective observational cohort study conducted in the Department of Gastroenterology at the First Affiliated Hospital of Air Force Medical University ( Fig. 1 ). The study protocol was reviewed and approved by the Institutional Ethics Committee of the First Affiliated Hospital of Air Force Medical University (KY20232344-F-1) before study initiation. Participants One hundred fifty-seven patients were recruited by convenience sampling from the hospital’s gastroenterology outpatient clinics. All patients provided written informed consent to participate. Eligible patients were adults aged 18–59 years diagnosed with new-onset mild-to-moderate active UC, defined by a Partial Mayo score of 3–10 according to the 2023 Chinese consensus guidelines, and patients for whom the treating physician had planned standard 5-ASA therapy, either as oral monotherapy or as a combination of oral and topical 5-ASA (suppositories or enemas). Patients also had to be willing and able to comply with the study procedures and to provide written informed consent. Exclusion criteria included recent use of prohibited medications: corticosteroids within 14 days, immunosuppressants within 90 days, or biologic therapies (e.g., infliximab, adalimumab, vedolizumab) within 60 days before enrollment; known allergy or intolerance to 5-ASA or other salicylates; significant comorbid conditions, such as a history of severe hepatic, renal, cardiac, pulmonary, hematologic, or pancreatic disease, or active malignancy; pregnancy or lactation (women who were pregnant or breastfeeding were excluded); and withdrawal of consent at any point before or during the study. Based on previous studies investigating clinical response rates to 5-ASA therapy in mild-to-moderate ulcerative colitis, we performed a power calculation with an alpha error of 0.05 and a power of 80% to determine the required sample size, and a minimum of 40 patients per group was needed, ensuring adequate statistical power to detect between-group differences. Grouping All participants received standard-of-care 5-ASA therapy as their initial treatment for UC. Depending on clinical need, this consisted of either oral 5-ASA alone or a combination of oral plus topical 5-ASA (5-ASA suppositories or enemas) at doses within the range of 2-4 g/day, as determined by the outpatient doctor. The cohort was observed without any experimental intervention, and patients were grouped based on the timing of their first post-treatment follow-up assessment. In routine practice, the first follow-up visit occurred at either approximately 4, 8, or 12 weeks after starting 5-ASA; accordingly, patients were stratified into three groups: Week 4 assessment group (group 1: W4), Week 8 assessment group (group 2: W8), and Week 12 assessment group (group 3: W12). Following each disease activity assessment, clinicians dynamically titrated 5-ASA therapy, adjusting doses of both oral and topical formulations based on treatment response. Throughout the 12-week intervention period, no patients transitioned to biologic therapy due to anticipated individual response variability in this newly diagnosed mild-to-moderate UC cohort. After 12 weeks of 5-ASA treatment, biologic agents were initiated in partial non-responders. Outcomes The primary outcomes were the change in clinical symptom severity from baseline to Week 12 (as measured by the Partial Mayo score (PMS)[16]), and the rates of clinical response and clinical remission at Week 12. For this study, clinical response was defined as a decrease in the PMS of ≥3 points or ≥30% from the baseline value (with an accompanying decrease of at least 1 point in the rectal bleeding subscore and an absolute rectal bleeding score ≤1), and clinical remission was defined as a total PMS ≤2 with no individual subscore >1. The secondary outcomes included changes in inflammatory biomarkers (hs-CRP and ESR levels) from baseline over the follow-up period, fecal occult blood (FOB) status (conversion to FOB-negative as an indicator of mucosal healing), any adjustments in mesalamine dosage or escalation of therapy (such as addition of corticosteroids or other medications) during the 12-week treatment phase, and changes in safety laboratory parameters (particularly liver and renal function tests) to monitor drug safety. Outcomes were assessed for both the short-term induction phase (up to 12 weeks) and longer-term maintenance through 24 weeks as appropriate. All the laboratory tests and colonoscopy examinations of the patients were conducted in the Department of Gastroenterology at the First Affiliated Hospital of Air Force Medical University. Statistical Analysis Descriptive statistics include demographic and clinical characteristics. Continuous variables are presented as mean ± SD (normally distributed) or median (range) (non-normal), while categorical variables are presented as frequencies (proportions). Independent group comparisons used chi-square tests for categorical variables, and Student’s t-test or Mann-Whitney U test for normal/non-normal continuous variables, respectively. Multi-group comparisons used chi-square tests for categorical variables, and One-way ANOVA test or Kruskal-Wallis test for normal/non-normal continuous variables, respectively. Paired comparisons between two time points of the same group employed the Wilcoxon signed-rank test for non-normal continuous variables. All statistical tests were two-sided, with a significance threshold set at p < 0.05. For any participants with missing data, they were excluded from the respective analyses, adopting a complete-case analysis approach. Data was analyzed using IBM SPSS Statistics software, version 25.0, and GraphPad Prism software (Version 10.4.1). Results All UC outpatients in Xijing Hospital were screened, and 157 patients with newly diagnosed mild-to-moderate active UC were included in the study (Fig. 1 ). Eligible patients aged 18–59 years, treated with either oral 5-ASA monotherapy or a combination of oral and topical 5-ASA (suppositories or enemas), were stratified according to the timing of their first follow-up visit into three groups: 4-week assessment group (Group 1: W4; N = 41), 8-week assessment group (Group 2: W8; N = 40), and 12-week assessment group (Group 3: W12; N = 42). During the initial 3-month treatment period, 34 patients discontinued follow-up: 8 switched to other treatments, and 26 were lost to follow-up. Among the remaining patients, 11 transitioned to biologics during the subsequent 24-week observation period. Baseline characteristics were comparable across groups. On average, clinical disease activity was mild at study entry (Table 1 , Table S1 ). Table 1 Baseline characteristics W4 (N = 41) W8 (N = 40) W12 (N = 42) P-value Age (years) 0.788 44 (31.5, 56) 43 (35.25, 58.75) 41.5 (34.75, 59) Gender 0.849 Male 24 (58.5%) 21 (52.5%) 24 (57.1%) Female 17 (41.5%) 19 (47.5%) 18 (42.9%) Extent 0.240 E1 28 (68.3%) 21 (52.5%) 20 (47.6%) E2 6 (14.6%) 9 (22.5%) 14 (33.3%) E3 7 (17.1%) 10 (25%) 8 (19.0%) Partial Mayo score 0.663 4 (3, 5) 3 (3, 5) 3 (3, 5) UCEIS 0.122 4 (3, 5) 4 (3, 5) 3 (2.75, 4) Disease activity 0.248 Mild 15 (36.6%) 19 (47.5%) 23 (54.8%) Moderate 26 (63.4%) 21 (52.5%) 19 (45.2%) Treatment medications received Oral 5-ASA 41 (100%) 40 (100%) 42 (100%) 5-ASA suppositories 31 (75.6%) 28 (70%) 26 (61.9%) 0.397 5-ASA enemas 1 (2.4%) 2 (5%) 3 (7.1%) 0.609 Probiotics 10 (24.4%) 15 (37.5%) 18 (42.9%) 0.194 Initial dose of oral 5-ASA (g/d) 0.053 3.39 ± 0.49 3.25 ± 0.69 3.05 ± 0.73 Extraintestinal manifestations 0.510 Joint 3 (7.3%) 0 (0.0%) 3 (7.1%) Liver 3 (7.3%) 4 (10%) 1 (2.4%) Skin 2 (4.9%) 1 (2.5%) 2 (4.8%) Symptom severity was monitored using the PMS at Weeks 4, 8, and 12 to assess short-term disease control. By Week 12, PMS values converged across all groups, with no significant differences observed (median 1.0 (0.0, 2.0) vs. 1.0 (0.0, 2.0) vs. 2.0 (0.0, 2.0); p = 0.2631) (Fig. 2 A). In the W4 group, symptom severity decreased significantly as early as Week 4 (median 2.0 (1.0, 2.0)) compared to baseline (median 4.0 (4.0, 6.0)) (p < 0.0001). This early improvement was substantial, and a further reduction by Week 8 was also significant (W8: median 2.0 (1.0, 2.0) vs W4: median 1.0 (0.0, 2.0)) (p = 0.0146). From Week 8 to Week 12, PMS remained stable at low levels (W8: median 1.0 (0.0, 2.0) vs W12: median 1.0 (0.0, 2.0)) (p = 0.7939) (Fig. 2 B). These findings indicate that all patients achieved similar disease control by Week 12, irrespective of initial follow-up timing, and that most improvement occurred within the first 4 weeks. In addition, as shown in Fig. 2 C, early clinical response rates (PMS reduction ≥ 3 points) of three groups differed according to the respective timing of their first follow-up (68.29% vs. 57.50% vs. 52.38%, p = 0.3228). Although these differences were not statistically significant, the trend suggests that earlier follow-up may better capture early symptomatic improvement. By Week 12, clinical remission rates (PMS ≤ 2) were high across all groups without significant differences (82.93% vs. 80.00% vs. 78.57%, p = 0.8783) (Fig. 2 D). Furthermore, the distribution of individual PMS changes within 12 weeks (categorized as decrease, maintenance, or increase) did not differ significantly across groups (p = 0.6124). The proportion of patients experiencing PMS decrease was highest in the W4 group (90.24%), followed by W8 (82.50%) and W12 (80.95%). Conversely, PMS increase proportions progressively rose across groups (W4: 2.44%; W8: 5.00%; W12: 9.52%), while maintenance proportions were 7.32%, 12.50%, and 9.52% respectively (Fig. 2 E). This distribution suggests that absence of early follow-up may allow unmitigated disease activity to persist, while earlier follow-up (as in the W4 group) was associated with more consistently favorable outcomes. These above findings support scheduling an initial follow-up at 4 weeks to improve short-term disease control in mild-to-moderate UC. We next examined inflammation markers to evaluate the physiological response to treatment. High-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) declined substantially from baseline to Week 12 in all groups (Fig. 3 A-B). ESR showed a statistically significant reduction only in the W4 group (median: 8.00 (6.00, 10.00) to 7.00 (4.25, 10.75); p = 0.0054), with non-significant reductions in W8 (7.00 (4.00–12.00) to 5.00 (2-9.5); p = 0.3172) and W12 (8.00 (6.00–12.00) to 6.00 (4–10); p = 0.1190). Similarly, hs-CRP reductions were not significant in any group. At Week 12, ESR levels did not differ significantly across the W4, W8, and W12 groups (p = 0.4153). However, a significant difference in hs-CRP levels was observed among the groups (p = 0.0284). Post-hoc pairwise comparisons revealed that the W4 group had significantly lower hs-CRP levels than the W12 group (p = 0.0256). These findings suggest that while ESR indicated comparable inflammation control across all follow-up schedules, the lower hs-CRP levels in the W4 group relative to the W12 group suggest that the timing of follow-up may influence hs-CRP-based assessment of inflammation control. In the W4 and W8 groups, inflammatory markers reached their lowest levels at Week 8, followed by a slight rebound by Week 12. In addition, at the first assessment, approximately half of the patients in each group remained positive for FOB, with no significant differences between groups (43.90% vs. 42.50% vs. 45.24%; p = 0.9693) (Fig. 3 C). Thus, delaying the first evaluation did not markedly increase the proportion of patients with resolved rectal bleeding. By Week 12, FOB positivity declined in all groups (Fig. 3 D). Patients in the W4 group, who received earlier assessments and potentially earlier treatment adjustments, showed higher FOB negativity rates compared to the W8 and W12 groups (53.66% vs. 42.50% vs.45.24%; p = 0.5753), suggesting greater mucosal healing. Although this trend did not reach statistical significance, the gradient supports the potential benefit of early follow-up, and more frequent early evaluation may promote faster and more complete mucosal healing during induction therapy. Early assessment also influenced medication management. Figure 4 A illustrates the trajectory of mean daily 5-aminosalicylic acid (5-ASA) dosing per patient stratified by assessment timing groups. Initial dosing was comparable across all three groups (W4: 3.29 g/day; W8: 3.23 g/day; W12: 3.05 g/day; p > 0.05) ( Fig. 4 A ) . At the 4-week assessment, the W4 group underwent significant dose reduction to 2.56 g/day. By week 12, this further decreased to 2.22 g/day, approaching the minimal maintenance dose for 5-ASA. The W8 group reduced dosing to 2.51 g/day at week 8, closely aligning with the W4 group’s week-4 levels. In contrast, the W12 group maintained a stable dose of 3.05 g/day throughout the 12 weeks. Consistently, the cumulative oral 5-ASA intake per patient over 3 months was significantly lower in the W4 group, while W8 and W12 groups had higher and comparable total exposure (median 240 (210, 270) vs. 255 (240, 330) vs. 270 (225, 360); p = 0.0422) (Fig. 4 B). This reduction translated into substantial cost savings: by month 3, medication expenditure per patient in the W4 group decreased by 32.5% compared to month 1. Over the 3-month induction phase, the W4 group saved approximately 400 CNY per patient relative to both later-assessment groups. At first follow-up dose adjustments, the W4 group showed higher reduction rates (82.93% reduction vs 14.63% stable vs 2.44% escalation) than the W8 group (67.50% vs 30.00% vs 2.50%), indicating earlier intervention increases 5-ASA optimization. Moreover, as shown in Fig. 4 C, the distribution of dose adjustments after Week 12 assessment further reflects the impact of follow-up timing. 82.93% of patients in the W4 group received a dose reduction at Week 12, compared to 70.00% and 71.43% in the W8 and W12 groups. More patients in the W12 group even underwent an escalation (0% vs. 5.00% vs. 9.52%). Despite the higher cumulative dosing in the W12 group, no adverse effects on liver function were observed (Fig. 4 D). After 12 weeks, liver function parameters were comparable across all groups. Likewise, renal function remained stable with no significant group differences (Fig. 4 E). Collectively, more frequent follow-up facilitated earlier dose reductions and lower cumulative drug exposure without affecting hepatic or renal safety over 12 weeks. To determine whether follow-up timing influenced long-term outcomes, we assessed key clinical and endoscopic measures at 24 weeks post-treatment. At 24 weeks after completion of initial 5-ASA therapy, key clinical and endoscopic outcomes were evaluated across all follow-up groups. Endoscopic disease activity, measured by the UCEIS[ 17 ], was low and did not differ significantly between groups (median 4(3, 5.25) vs. 4(3, 6) vs. 4(2.25, 5.25); p = 0.850) (Fig. 5 A). The daily oral 5-ASA maintenance dose at Week 24 was also comparable (median 2(1, 3) vs. 2(2, 3) vs. 2(2, 3); p = 0.3386) (Fig. 5 B), indicating that initial follow-up timing had no effect on long-term medication requirements. Clinical symptom severity, assessed by the PMS, remained uniformly mild with no significant group differences (median 0(0, 2) vs. 2(0, 3) vs. 2(0, 3); p = 0.2715) (Fig. 5 C). ESR values were equivalent across the W4, W8, and W12 groups at the 6-month mark (p = 0.933) (Fig. 5 D), showing no group-specific differences in systemic inflammation. In contrast, hs-CRP levels at 24 weeks were significantly lower in the W4 group compared to both W8 and W12 groups ((median 0.7770(0.7770, 1.073) vs. 1.025(0.7770, 1.693) vs. 1.070(0.7770, 1.790); p = 0.0453) ( Fig. 5 E ) , while W8 and W12 groups did not differ from each other, suggesting that earlier assessment may be associated with better long-term suppression of inflammatory activity. Mucosal healing, reflected by FOB negativity, showed no significant differences between groups (46.34% vs. 42.5% vs. 40.47%; p = 0.8609) ( Fig. 5 F ) . Taken together, these results indicate that despite differences in follow-up timing, 6-month clinical remission, endoscopic healing, inflammatory marker (except hs-CRP), and maintenance dose requirements were comparable across groups. Standard follow-up at 8 or 12 weeks was as effective as an early 4-week follow-up for long-term disease control in mild-to-moderate UC. Discussion In this study, the timing of initial follow-up had a clear impact on the early course of mild-to-moderate UC. The W4 group showed an early, rapid decline in PMS by Week 4 and fewer patients with persistent or worsening symptoms through 3 months. This finding underscores the clinical value of early follow-up in achieving prompt symptomatic control. Current practice in mild UC often waits ~ 12 weeks to evaluate response[ 18 ], but our data suggest this may leave some patients with unmitigated disease activity for too long. Our results make a compelling case for an initial assessment at 4 weeks to capture treatment non-responders and intensify therapy if needed. By Week 12, patients in the W4 group exhibited the highest rate of FOB negativity, which serves as a surrogate marker for mucosal healing[ 19 ], among the groups. However, this difference was not statistically significant. This trend is noteworthy given modern treat-to-target strategies emphasizing mucosal healing as a key endpoint. Endoscopic healing correlates with significantly improved long-term outcomes in UC[ 20 ]. Our findings imply that frequent early follow-up could promote mucosal healing, a vital element of long-term disease management. A key advantage of the 4-week follow-up strategy was its ability to optimize 5-ASA therapy and minimize medication exposure without sacrificing disease control. The W4 group responded quickly to clinical improvement, allowing them to taper their doses early and achieve an 80% success rate of dose reduction within 3 months. Consequently, they maintained a lower overall 5-ASA dosage than the groups monitored later. Importantly, this decreased drug exposure did not lead to increased relapse or inflammation at 3 months, indicating that many patients could be safely de-escalated to maintenance doses sooner. This has practical implications for patient adherence and safety. Nearly half of UC patients express a desire to reduce their 5-ASA pill burden, and a high pill count is a known factor in non-adherence in UC[ 21 ]. Therefore, earlier dose reduction not only limits drug exposure and potential costs but may also enhance adherence and patient satisfaction with treatment. Despite the differences observed in the early phase, by 24 weeks, all three follow-up strategies resulted in equivalent key outcomes in our mild-to-moderate UC patients. These findings suggest that standard follow-up at 8–12 weeks is sufficient to eventually attain remission in mild UC under optimal therapy, which provides reassurance about the current standard practice. It also suggests that early follow-up mainly confers a temporal benefit, reducing disease burden sooner, rather than a categorical difference in whether remission is achieved. However, it is notable that the significantly lower CRP in the W4 group at 24 weeks hints that early intervention may confer a deeper, more durable remission[ 19 , 22 ]. This subtle biochemical advantage did not manifest in different clinical or endoscopic outcomes by 6 months, possibly due to the mild disease severity across all arms. Longer-term follow-up would be valuable to see if the initial CRP advantage in the W4 group translates to fewer relapses or complications over 1–2 years. Implementing a 4-week early follow-up strategy is not without challenges. Our findings revealed a subtle but essential consideration – the potential for over-adjustment of therapy. In the W4 group (and to a lesser extent, the W8 group), inflammatory markers dropped rapidly by 8 weeks but exhibited a slight rebound by 12 weeks. If we reduce therapy at the first sign of improvement, we risk a “bounce-back” of disease activity. However, it emphasizes the importance of clear criteria and caution in early decision-making. An overlooked benefit of frequent early follow-up is improving patient–physician communication and education. Beyond the pharmacologic adjustments made at the 4-week visit, the interaction may contribute to better outcomes[ 21 , 23 ]. Patients seen earlier have more opportunity to discuss their symptoms, medication usage, diet, and concerns, reinforcing treatment plans and building trust. By early check-in, we suspect patients in the W4 group received additional counseling on 5-ASA adherence, lifestyle, and what to expect in their disease course. This could partly explain their superior short-term symptom control, as engagement and understanding often translate into better self-management. The strengths of this study include: (1) Firstly, this work represents the first investigation to establish the optimal timing for 5-ASA efficacy assessment in patients with mild-to-moderate ulcerative colitis (UC), providing actionable guidance for treatment monitoring protocols. (2) Secondly, concurrently evaluating both short-term clinical symptom resolution (within 3 months) and 24-week long-term outcomes offers a comprehensive perspective on therapeutic durability. However, there are also several limitations to this study. (1) Firstly, its single-center design and relatively small patient cohort may restrict the generalizability of findings to broader clinical populations. (2) Secondly, dose adjustments relied heavily on physicians’ clinical expertise, introducing potential variability in therapeutic decision-making that was not systematically quantified. (3) Thirdly, the inherent limitations of the observational design must be acknowledged. The most significant is the potential for confounding due to the non-randomized allocation to follow-up groups, despite the lack of significant baseline differences between groups (Table 1 , Table S1 ). Performance bias is possible as physicians and patients were not blinded to the follow-up schedule; however, the enhanced patient education in the 4-week group can be considered an integral benefit of the strategy itself. Attrition bias was mitigated as the proportion of patients lost to follow-up was comparable across groups. Furthermore, the use of objective biomarkers (hs-CRP, ESR) helps substantiate the findings from subjective clinical scores. However, our study included a well-characterized cohort of patients with mild-to-moderate UC, and the standard 5-ASA therapy employed is first-line treatment worldwide. Therefore, our findings remain applicable to other clinical environments. Future multi-center studies with larger, more diverse cohorts and standardized adjustment protocols are warranted to validate the generalizability of our conclusions. Conclusions The results of this study support a shift towards earlier initial follow-up for patients with mild-to-moderate UC starting 5-ASA therapy. Presently, some international guidelines consider a 3-month evaluation acceptable in mild disease. However, this study's results significantly benefit assessing patients as early as 4 weeks. These benefits include faster symptom relief, a trend toward quicker mucosal healing, reduced medication exposure through prompt dose adjustments, and an improved patient experience, all achieved without sacrificing long-term outcomes. This has direct clinical relevance: patients enjoy a better quality of life sooner, and clinicians can identify inadequate responders by one month, enabling earlier changes to alternative therapy if needed. Therefore, we recommend that mild-to-moderate UC patients be evaluated around 4 weeks after starting a new treatment, instead of the traditional 2–3 months’ timeframe, to confirm response or modify the treatment plan. Abbreviations 5-ASA: 5-Aminosalicylic Acid UC: Ulcerative Colitis PMS: Partial Mayo Score hs-CRP: High-sensitivity C-reactive Protein ESR: Erythrocyte Sedimentation Rate FOB: Fecal Occult Blood UCEIS: Ulcerative Colitis Endoscopic Index of Severity RCT: Randomized Controlled Trial ECCO: European Crohn's and Colitis Organization SD: Standard Deviation ANOVA: Analysis of Variance ALT: Alanine Aminotransferase AST: Aspartate Aminotransferase Tbil: Total Bilirubin Dbil: Direct Bilirubin Ibil: Indirect Bilirubin ALP: Alkaline Phosphatase TP: Total Protein Declarations Ethics approval and consent to participate: This study was conducted according to the guidelines of the Declaration of Helsinki, and proved by the Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University (reference number: KY20232344-F-1). Informed consent was obtained from all patients. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This work was supported by the following Independent Funds: the Natural Science Foundation of Shaanxi Province, Key Industrial Innovation Project Fund (2023-ZDLSF-44); the National Natural Science Foundation of China General Program (No. 82370588); National Natural Science Foundation of China Major Research Program Integration Project (No. 92259302); Independent Funds of the Key Laboratory (CBSKL2022ZZ34); The innovative medical research boosting project (XJZT25CX41); Special Project for Clinical New Technologies of Xijing Hospital (2024XJSY17). Authors' contributions: (1) study concept and design: Y.D., F.W. and J.L.; Acquisition of data: Y.D., J.Z., T.Z., J.H. and Y.S.; Analysis and interpretation of data: Y.D., T.Z., X.L. and J.L.; (2) drafting and critical revision of the article for important intellectual content: Y.D., J.Z., T.W. and J.L.; All authors have read and agreed to the published version of the manuscript. Acknowledgements: Not applicable. References Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet. 2023;402:571–84. doi: 10.1016/s0140-6736(23)00966-2 Hracs L, Windsor JW, Gorospe J, et al. Global evolution of inflammatory bowel disease across epidemiologic stages. Nature. 2025;642:458–66. doi: 10.1038/s41586-025-08940-0 Voelker R. What Is Ulcerative Colitis? Jama. 2024;331:716. doi: 10.1001/jama.2023.23814 Zheng K, Zhang S, Wang C, et al. Health-related quality of life in Chinese patients with mild and moderately active ulcerative colitis. 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Full, Partial, and Modified Permutations of the Mayo Score: Characterizing Clinical and Patient-Reported Outcomes in Ulcerative Colitis Patients. Crohns Colitis 360. 2021;3:otab007. doi: 10.1093/crocol/otab007 Travis SP, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013;145:987–95. doi: 10.1053/j.gastro.2013.07.024 D'Amico F, Magro F, Dignass A, et al. Practical management of mild-to-moderate ulcerative colitis: an international expert consensus. Expert Rev Gastroenterol Hepatol. 2024;18:421–30. doi: 10.1080/17474124.2024.2397650 Clough J, Colwill M, Poullis A, et al. Biomarkers in inflammatory bowel disease: a practical guide. Therap Adv Gastroenterol. 2024;17:17562848241251600. doi: 10.1177/17562848241251600 Parkes G, Ungaro RC, Danese S, et al. Correlation of mucosal healing endpoints with long-term clinical and patient-reported outcomes in ulcerative colitis. J Gastroenterol. 2023;58:990–1002. doi: 10.1007/s00535-023-02013-7 Amano T, Yoshihara T, Nishida T, et al. Optimizing 5-Aminosalicylic Acid Maintenance Treatment in Ulcerative Colitis from the Patient and Physician Perspective: A Cross-sectional Multicenter Study. Crohns Colitis 360. 2025;7:otaf038. doi: 10.1093/crocol/otaf038 Chang S, Malter L, Hudesman D. Disease monitoring in inflammatory bowel disease. World J Gastroenterol. 2015;21:11246–59. doi: 10.3748/wjg.v21.i40.11246 Peters LA, Brown EM. The relationship between illness identity and the self-management of Inflammatory Bowel Disease. Br J Health Psychol. 2022;27:956–70. doi: 10.1111/bjhp.12584 Additional Declarations No competing interests reported. Supplementary Files SupplementaryData.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 11 May, 2026 Reviews received at journal 17 Mar, 2026 Reviewers agreed at journal 10 Mar, 2026 Reviewers agreed at journal 22 Dec, 2025 Reviewers agreed at journal 19 Dec, 2025 Reviews received at journal 10 Dec, 2025 Reviewers agreed at journal 07 Dec, 2025 Reviewers invited by journal 07 Dec, 2025 Editor assigned by journal 06 Nov, 2025 Submission checks completed at journal 06 Nov, 2025 First submitted to journal 04 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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10:51:15","extension":"html","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":105636,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/2ab866f3a1d4ad26a1c7f72e.html"},{"id":97874291,"identity":"64bb911b-0df4-4e99-9edc-d19dd3da5737","added_by":"auto","created_at":"2025-12-10 10:51:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":174170,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram illustrating patient enrollment, allocation to follow-up timing groups (4-, 8-, or 12-week), and attrition during the 36-week observational study of 5-ASA therapy in mild-to-moderate ulcerative colitis.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/dc66e5ded11ed9c2709a3783.png"},{"id":97900661,"identity":"78108ae3-7277-4ab1-9fbd-58e3dea395f1","added_by":"auto","created_at":"2025-12-10 15:45:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":185198,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of efficacy with different adjustment intervals in patients with UC (W4: N=41; W8: N=40; W12: N=42). A-B.\u003c/strong\u003e Dynamic changes in PMS within 3 months of 5-ASA treatment after initial onset; \u003cstrong\u003eC. \u003c/strong\u003eClinical response rate (PMS reduction ≥3 points) at first follow-up (W4: 4 weeks; W8: 8 weeks; W12: 12 weeks); \u003cstrong\u003eD. \u003c/strong\u003eClinical remission rate (PMS ≤2 points) 3 months after initial onset; \u003cstrong\u003eE. \u003c/strong\u003eProportion of patients showing increased, decreased, or stable PMS within 3 months of 5-ASA treatment. (Statistical analysis: Kruskal-Wallis test/Wilcoxon test/Chi-square test; *P\u0026lt;0.05, ****P\u0026lt;0.0001; ns: not significant)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/32136761381984da6859dfaf.png"},{"id":97900626,"identity":"e76a7c63-87fa-4517-9c5c-0be36b3321ed","added_by":"auto","created_at":"2025-12-10 15:45:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":193829,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of different adjustment intervals on inflammatory markers and FOB in UC patients (W4: N=41; W8: N=40; W12: N=42). A. \u003c/strong\u003eTemporal changes in hs-CRP within 3 months of 5-ASA therapy after initial onset; \u003cstrong\u003eB. \u003c/strong\u003eTemporal changes in ESR within 3 months of 5-ASA therapy after initial onset;\u003cstrong\u003e C.\u003c/strong\u003e FOB positivity rate at first follow-up (W4: 4 weeks; W8: 8 weeks; W12: 12 weeks); \u003cstrong\u003eD. \u003c/strong\u003eFOB positivity rate after 3 months of 5-ASA therapy. (Statistical analysis: Kruskal-Wallis test/Wilcoxon test/Chi-square test; **P\u0026lt;0.01, ns: not significant)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/f0017bfa2df98cc2e617c919.png"},{"id":97874298,"identity":"45028d6a-2f9e-4ed2-a6a6-819adc71370e","added_by":"auto","created_at":"2025-12-10 10:51:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":179017,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of different adjustment intervals on the therapeutic dosage and safety of 5-ASA (W4: N=41; W8: N=40; W12: N=42).\u003c/strong\u003e \u003cstrong\u003eA.\u003c/strong\u003e Dynamic changes in patients' daily oral 5-ASA dosage (g/day) during the 3-month treatment period; \u003cstrong\u003eB.\u003c/strong\u003e Cumulative total oral 5-ASA intake (g) among patients over 3 months of treatment; \u003cstrong\u003eC.\u003c/strong\u003e Proportion of patients exhibiting increased, decreased, or unchanged 5-ASA dosage relative to the initial dose after 3 months of treatment; \u003cstrong\u003eD.\u003c/strong\u003e Changes in liver function parameters after 3 months of treatment (ALT, AST, Tbil, Dbil, Ibil, ALP, TP); \u003cstrong\u003eE.\u003c/strong\u003e Changes in renal function parameters after 3 months of treatment (Urea, Creatinine). (Statistical methods: Kruskal-Wallis test/Wilcoxon test/Chi-square test; *P\u0026lt;0.05, *P\u0026lt;0.05, ns: not significant)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/c14c2f828f3e372e4d8e2304.png"},{"id":97874306,"identity":"074219e8-495d-4a3c-bae5-97b2e2cfff22","added_by":"auto","created_at":"2025-12-10 10:51:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":195350,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of follow-up outcomes at 24 weeks after treatment completion among patients with different adjustment cycles (W4: N=38; W8: N=36; W12: N=38). A. UC endoscopic index of severity (UCEIS) score at 24 weeks after treatment completion; B. Daily 5-ASA maintenance dose (g/day) at 24 weeks after treatment completion; C. PMS at 24 weeks after treatment completion; D. Erythrocyte sedimentation rate (ESR, mm/h) at 24 weeks after treatment completion; E. High-sensitivity C-reactive protein (hs-CRP, mg/L) level at 24 weeks after treatment completion;F. The FOB analysis was performed at 24 weeks after treatment completion. Statistical analysis was performed using the \u003c/strong\u003eKruskal-Wallis test/Wilcoxon test/Chi-square test\u003cstrong\u003e, with significance levels indicated as *P\u0026lt;0.05, \u003c/strong\u003ens: not significant.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/575e0e155f9c019bd8625351.png"},{"id":98421143,"identity":"aefc7e38-f97d-49e0-81f3-1da573f43698","added_by":"auto","created_at":"2025-12-17 16:24:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2038404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/b34b4a4c-114b-41c5-a168-f122ea7abac9.pdf"},{"id":97874293,"identity":"3ab9434d-4591-4457-aa89-3052886b094d","added_by":"auto","created_at":"2025-12-10 10:51:15","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18782,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData.docx","url":"https://assets-eu.researchsquare.com/files/rs-7873738/v1/88f2017332014d60871d15b6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"What is the Optimal Timing to Assess the Effect of 5-ASA in Patients with Mild-to- Moderate Ulcerative Colitis? A Single-Center Prospective Observational Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUlcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon that imposes a substantial global health burden[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In 2023, the worldwide prevalence of UC was estimated at roughly 5\u0026nbsp;million cases[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and sustained growth in UC prevalence persists globally across all epidemiological stages[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Typical clinical manifestations of UC include abdominal pain, diarrhea, mucopurulent bloody stools, and tenesmus; some patients also exhibit systemic symptoms such as fatigue, weight loss, and extraintestinal manifestations[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Even mild-to-moderate UC can significantly impair quality of life[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Ongoing inflammation also carries long-term risks, as repeated disease flares can cause physical and psychological harm and lead to cumulative bowel damage[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These epidemiological and clinical realities underscore the pressing need for optimized management strategies in UC.\u003c/p\u003e\u003cp\u003eContemporary practice guidelines recommend combined systemic and topical 5-aminosalicylic acid (5-ASA) as the first-line induction therapy for mild-to-moderate UC[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, an evidence-based standard for the assessment timing of UC patients receiving 5-ASA has not been firmly established. In current clinical practice, follow-up intervals after initiating 5-ASA vary widely. Some clinicians schedule the first evaluation for patients with mild disease at 8\u0026ndash;12 weeks. However, delaying efficacy assessment for two to three months may result in prolonged uncontrolled mucosal inflammation in suboptimal responders. In contrast, good responders incur unnecessary medication costs through sustained high-dose therapy. With the emergence of the \u0026ldquo;treat-to-target\u0026rdquo; concept, there is increasing recognition that earlier identification of inadequate responders allows clinicians to intervene sooner[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, it remains unclear how soon is sufficiently early to balance giving 5-ASA adequate time to act versus avoiding undue delay in non-responders.\u003c/p\u003e\u003cp\u003eA randomized controlled trial (RCT) indicated that clinical remission rates after 5-ASA treatment were 18%\u0026ndash;25% at three weeks, increasing markedly to 35%\u0026ndash;43% at six weeks[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, the American Gastroenterological Association consensus recommends assessing symptom improvement at 4\u0026ndash;8 weeks of 5-ASA therapy to guide further medication decisions[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The American College of Gastroenterology Clinical Guidelines issued a key concept statement that patients with mildly to moderately active ulcerative colitis should be reassessed within 8 weeks to determine their response to induction therapy[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In the pharmacodynamic data (ASCEND II trial), the median time to cease rectal bleeding was nine days in patients receiving 4.8 g/d 5-ASA, and 16 days in patients receiving 2.4 g/d[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The finding suggests that the onset window for therapeutic action of 5-ASA is relatively short; clinical benefit generally emerges within 2\u0026ndash;4 weeks after treatment initiation[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Another RCT demonstrated that among patients without improvement in rectal bleeding or stool frequency after 14 days of adequate 5-ASA treatment, 56% and 75%, respectively, continued to show no improvement after six weeks[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, 74%\u0026ndash;86% of patients achieving clinical remission by day 14 maintained remission subsequently. These findings support the concept that early assessment of 5-ASA efficacy in moderately active UC can inform therapeutic decision-making. Based on this evidence, the European Crohn's and Colitis Organization (ECCO) suggests escalation therapy in UC patients without symptom improvement after 10\u0026ndash;14 days of treatment[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, Orchard et al. found that while 10\u0026ndash;14 days of therapy may suffice for symptomatic improvement, rectal bleeding and abnormal stool frequency resolution requires 19\u0026ndash;29 days[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This raises concern that efficacy assessment at 10\u0026ndash;14 days might be premature for mild-to-moderate UC patients, potentially leading to inappropriate step-down therapy. Moreover, a randomized controlled trial demonstrated a continued rapid increase in clinical remission rates between weeks 2\u0026ndash;4 post-treatment, with this upward trend plateauing only after week 4[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These findings further indicate that evaluation at 2 weeks risks misclassifying 5-ASA-responsive patients as suboptimal responders. This conflict creates a clinical challenge: identify a \"sweet spot\" between allowing adequate drug response time, avoiding prolonged ineffective therapy in non-responders, and preventing premature de-escalation in responders.\u003c/p\u003e\u003cp\u003eTo resolve this, we conducted a single-center prospective observational cohort study to compare three evidence-based assessment timepoints to assess the impact of different initial assessment timing on 5-ASA treatment response in newly diagnosed UC patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eTrial design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was designed as a single-center, prospective observational cohort study conducted in the Department of Gastroenterology at the First Affiliated Hospital of Air Force Medical University (\u003cstrong\u003eFig. 1\u003c/strong\u003e). The study protocol was reviewed and approved by the Institutional Ethics Committee of the First Affiliated Hospital of Air Force Medical University (KY20232344-F-1) before study initiation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne hundred fifty-seven patients were recruited by convenience sampling from the hospital\u0026rsquo;s gastroenterology outpatient clinics. All patients provided written informed consent to participate. Eligible patients were adults aged 18\u0026ndash;59 years diagnosed with new-onset mild-to-moderate active UC, defined by a Partial Mayo score of 3\u0026ndash;10 according to the 2023 Chinese consensus guidelines, and patients for whom the treating physician had planned standard 5-ASA therapy, either as oral monotherapy or as a combination of oral and topical 5-ASA (suppositories or enemas). Patients also had to be willing and able to comply with the study procedures and to provide written informed consent. Exclusion criteria included recent use of prohibited medications: corticosteroids within 14 days, immunosuppressants within 90 days, or biologic therapies (e.g., infliximab, adalimumab, vedolizumab) within 60 days before enrollment; known allergy or intolerance to 5-ASA or other salicylates; significant comorbid conditions, such as a history of severe hepatic, renal, cardiac, pulmonary, hematologic, or pancreatic disease, or active malignancy; pregnancy or lactation (women who were pregnant or breastfeeding were excluded); and withdrawal of consent at any point before or during the study.\u0026nbsp;Based on previous studies investigating clinical response rates to 5-ASA therapy in mild-to-moderate ulcerative colitis, we performed a power calculation with an alpha error of 0.05 and a power of 80% to determine the required sample size, and a minimum of 40 patients per group was needed, ensuring adequate statistical power to detect between-group differences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGrouping\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants received standard-of-care 5-ASA therapy as their initial treatment for UC. Depending on clinical need, this consisted of either oral 5-ASA alone or a combination of oral plus topical 5-ASA (5-ASA suppositories or enemas) at doses within the range of 2-4 g/day, as determined by the outpatient doctor.\u0026nbsp;The cohort was observed without any experimental intervention, and patients were grouped based on the timing of their first post-treatment follow-up assessment. In routine practice, the first follow-up visit occurred at either approximately 4, 8, or 12 weeks after starting 5-ASA; accordingly, patients were stratified into three groups: Week 4 assessment group (group 1: W4), Week 8 assessment group (group 2: W8), and Week 12 assessment group (group 3: W12). Following each disease activity assessment, clinicians dynamically titrated 5-ASA therapy, adjusting doses of both oral and topical formulations based on treatment response. Throughout the 12-week intervention period, no patients transitioned to biologic therapy due to anticipated individual response variability in this newly diagnosed mild-to-moderate UC cohort. After 12 weeks of 5-ASA treatment, biologic agents were initiated in partial non-responders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcomes were the change in clinical symptom severity from baseline to Week 12 (as measured by the Partial Mayo score (PMS)[16]), and the rates of clinical response and clinical remission at Week 12. For this study, clinical response was defined as a decrease in the PMS of \u0026ge;3 points or \u0026ge;30% from the baseline value (with an accompanying decrease of at least 1 point in the rectal bleeding subscore and an absolute rectal bleeding score \u0026le;1), and clinical remission was defined as a total PMS \u0026le;2 with no individual subscore \u0026gt;1. The secondary outcomes included changes in inflammatory biomarkers (hs-CRP and ESR levels) from baseline over the follow-up period, fecal occult blood (FOB) status (conversion to FOB-negative as an indicator of mucosal healing), any adjustments in mesalamine dosage or escalation of therapy (such as addition of corticosteroids or other medications) during the 12-week treatment phase, and changes in safety laboratory parameters (particularly liver and renal function tests) to monitor drug safety. Outcomes were assessed for both the short-term induction phase (up to 12 weeks) and longer-term maintenance through 24 weeks as appropriate. All the laboratory tests and colonoscopy examinations of the patients were conducted in the Department of Gastroenterology at the First Affiliated Hospital of Air Force Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics include demographic and clinical characteristics. Continuous variables are presented as mean \u0026plusmn; SD (normally distributed) or median (range) (non-normal), while categorical variables are presented as frequencies (proportions). Independent group comparisons used chi-square tests for categorical variables, and Student\u0026rsquo;s t-test or Mann-Whitney U test for normal/non-normal continuous variables, respectively. Multi-group comparisons used chi-square tests for categorical variables, and One-way ANOVA test or Kruskal-Wallis test for normal/non-normal continuous variables, respectively. Paired comparisons between two time points of the same group employed the Wilcoxon signed-rank test for non-normal continuous variables. All statistical tests were two-sided, with a significance threshold set at p \u0026lt; 0.05. For any participants with missing data, they were excluded from the respective analyses, adopting a complete-case analysis approach. Data was analyzed using IBM SPSS Statistics software, version 25.0, and GraphPad Prism software (Version 10.4.1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAll UC outpatients in Xijing Hospital were screened, and 157 patients with newly diagnosed mild-to-moderate active UC were included in the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Eligible patients aged 18\u0026ndash;59 years, treated with either oral 5-ASA monotherapy or a combination of oral and topical 5-ASA (suppositories or enemas), were stratified according to the timing of their first follow-up visit into three groups: 4-week assessment group (Group 1: W4; N\u0026thinsp;=\u0026thinsp;41), 8-week assessment group (Group 2: W8; N\u0026thinsp;=\u0026thinsp;40), and 12-week assessment group (Group 3: W12; N\u0026thinsp;=\u0026thinsp;42). During the initial 3-month treatment period, 34 patients discontinued follow-up: 8 switched to other treatments, and 26 were lost to follow-up. Among the remaining patients, 11 transitioned to biologics during the subsequent 24-week observation period.\u003c/p\u003e\u003cp\u003eBaseline characteristics were comparable across groups. On average, clinical disease activity was mild at study entry (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e).\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\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eW4\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eW8\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eW12\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.788\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 (31.5, 56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (35.25, 58.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.5 (34.75, 59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.849\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (58.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (52.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (41.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (47.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (42.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtent\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.240\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (68.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (52.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (47.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (14.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (17.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (19.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePartial Mayo score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.663\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUCEIS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.122\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (2.75, 4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDisease activity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.248\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMild\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (36.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (47.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (54.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (63.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (52.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (45.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment medications received\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOral 5-ASA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5-ASA suppositories\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (75.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (61.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.397\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5-ASA enemas\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (2.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.609\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProbiotics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (24.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (42.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.194\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInitial dose of oral 5-ASA (g/d)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtraintestinal manifestations\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJoint\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (4.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSymptom severity was monitored using the PMS at Weeks 4, 8, and 12 to assess short-term disease control. By Week 12, PMS values converged across all groups, with no significant differences observed (median 1.0 (0.0, 2.0) vs. 1.0 (0.0, 2.0) vs. 2.0 (0.0, 2.0); p\u0026thinsp;=\u0026thinsp;0.2631) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). In the W4 group, symptom severity decreased significantly as early as Week 4 (median 2.0 (1.0, 2.0)) compared to baseline (median 4.0 (4.0, 6.0)) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). This early improvement was substantial, and a further reduction by Week 8 was also significant (W8: median 2.0 (1.0, 2.0) vs W4: median 1.0 (0.0, 2.0)) (p\u0026thinsp;=\u0026thinsp;0.0146). From Week 8 to Week 12, PMS remained stable at low levels (W8: median 1.0 (0.0, 2.0) vs W12: median 1.0 (0.0, 2.0)) (p\u0026thinsp;=\u0026thinsp;0.7939) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). These findings indicate that all patients achieved similar disease control by Week 12, irrespective of initial follow-up timing, and that most improvement occurred within the first 4 weeks. In addition, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, early clinical response rates (PMS reduction\u0026thinsp;\u0026ge;\u0026thinsp;3 points) of three groups differed according to the respective timing of their first follow-up (68.29% vs. 57.50% vs. 52.38%, p\u0026thinsp;=\u0026thinsp;0.3228). Although these differences were not statistically significant, the trend suggests that earlier follow-up may better capture early symptomatic improvement. By Week 12, clinical remission rates (PMS\u0026thinsp;\u0026le;\u0026thinsp;2) were high across all groups without significant differences (82.93% vs. 80.00% vs. 78.57%, p\u0026thinsp;=\u0026thinsp;0.8783) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Furthermore, the distribution of individual PMS changes within 12 weeks (categorized as decrease, maintenance, or increase) did not differ significantly across groups (p\u0026thinsp;=\u0026thinsp;0.6124). The proportion of patients experiencing PMS decrease was highest in the W4 group (90.24%), followed by W8 (82.50%) and W12 (80.95%). Conversely, PMS increase proportions progressively rose across groups (W4: 2.44%; W8: 5.00%; W12: 9.52%), while maintenance proportions were 7.32%, 12.50%, and 9.52% respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE). This distribution suggests that absence of early follow-up may allow unmitigated disease activity to persist, while earlier follow-up (as in the W4 group) was associated with more consistently favorable outcomes. These above findings support scheduling an initial follow-up at 4 weeks to improve short-term disease control in mild-to-moderate UC.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWe next examined inflammation markers to evaluate the physiological response to treatment. High-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) declined substantially from baseline to Week 12 in all groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-B). ESR showed a statistically significant reduction only in the W4 group (median: 8.00 (6.00, 10.00) to 7.00 (4.25, 10.75); p\u0026thinsp;=\u0026thinsp;0.0054), with non-significant reductions in W8 (7.00 (4.00\u0026ndash;12.00) to 5.00 (2-9.5); p\u0026thinsp;=\u0026thinsp;0.3172) and W12 (8.00 (6.00\u0026ndash;12.00) to 6.00 (4\u0026ndash;10); p\u0026thinsp;=\u0026thinsp;0.1190). Similarly, hs-CRP reductions were not significant in any group. At Week 12, ESR levels did not differ significantly across the W4, W8, and W12 groups (p\u0026thinsp;=\u0026thinsp;0.4153). However, a significant difference in hs-CRP levels was observed among the groups (p\u0026thinsp;=\u0026thinsp;0.0284). Post-hoc pairwise comparisons revealed that the W4 group had significantly lower hs-CRP levels than the W12 group (p\u0026thinsp;=\u0026thinsp;0.0256). These findings suggest that while ESR indicated comparable inflammation control across all follow-up schedules, the lower hs-CRP levels in the W4 group relative to the W12 group suggest that the timing of follow-up may influence hs-CRP-based assessment of inflammation control. In the W4 and W8 groups, inflammatory markers reached their lowest levels at Week 8, followed by a slight rebound by Week 12. In addition, at the first assessment, approximately half of the patients in each group remained positive for FOB, with no significant differences between groups (43.90% vs. 42.50% vs. 45.24%; p\u0026thinsp;=\u0026thinsp;0.9693) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Thus, delaying the first evaluation did not markedly increase the proportion of patients with resolved rectal bleeding. By Week 12, FOB positivity declined in all groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). Patients in the W4 group, who received earlier assessments and potentially earlier treatment adjustments, showed higher FOB negativity rates compared to the W8 and W12 groups (53.66% vs. 42.50% vs.45.24%; p\u0026thinsp;=\u0026thinsp;0.5753), suggesting greater mucosal healing. Although this trend did not reach statistical significance, the gradient supports the potential benefit of early follow-up, and more frequent early evaluation may promote faster and more complete mucosal healing during induction therapy.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEarly assessment also influenced medication management. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA illustrates the trajectory of mean daily 5-aminosalicylic acid (5-ASA) dosing per patient stratified by assessment timing groups. Initial dosing was comparable across all three groups (W4: 3.29 g/day; W8: 3.23 g/day; W12: 3.05 g/day; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA\u003cb\u003e)\u003c/b\u003e. At the 4-week assessment, the W4 group underwent significant dose reduction to 2.56 g/day. By week 12, this further decreased to 2.22 g/day, approaching the minimal maintenance dose for 5-ASA. The W8 group reduced dosing to 2.51 g/day at week 8, closely aligning with the W4 group\u0026rsquo;s week-4 levels. In contrast, the W12 group maintained a stable dose of 3.05 g/day throughout the 12 weeks. Consistently, the cumulative oral 5-ASA intake per patient over 3 months was significantly lower in the W4 group, while W8 and W12 groups had higher and comparable total exposure (median 240 (210, 270) vs. 255 (240, 330) vs. 270 (225, 360); p\u0026thinsp;=\u0026thinsp;0.0422) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). This reduction translated into substantial cost savings: by month 3, medication expenditure per patient in the W4 group decreased by 32.5% compared to month 1. Over the 3-month induction phase, the W4 group saved approximately 400 CNY per patient relative to both later-assessment groups. At first follow-up dose adjustments, the W4 group showed higher reduction rates (82.93% reduction vs 14.63% stable vs 2.44% escalation) than the W8 group (67.50% vs 30.00% vs 2.50%), indicating earlier intervention increases 5-ASA optimization. Moreover, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC, the distribution of dose adjustments after Week 12 assessment further reflects the impact of follow-up timing. 82.93% of patients in the W4 group received a dose reduction at Week 12, compared to 70.00% and 71.43% in the W8 and W12 groups. More patients in the W12 group even underwent an escalation (0% vs. 5.00% vs. 9.52%). Despite the higher cumulative dosing in the W12 group, no adverse effects on liver function were observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). After 12 weeks, liver function parameters were comparable across all groups. Likewise, renal function remained stable with no significant group differences (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE). Collectively, more frequent follow-up facilitated earlier dose reductions and lower cumulative drug exposure without affecting hepatic or renal safety over 12 weeks.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTo determine whether follow-up timing influenced long-term outcomes, we assessed key clinical and endoscopic measures at 24 weeks post-treatment. At 24 weeks after completion of initial 5-ASA therapy, key clinical and endoscopic outcomes were evaluated across all follow-up groups. Endoscopic disease activity, measured by the UCEIS[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], was low and did not differ significantly between groups (median 4(3, 5.25) vs. 4(3, 6) vs. 4(2.25, 5.25); p\u0026thinsp;=\u0026thinsp;0.850) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). The daily oral 5-ASA maintenance dose at Week 24 was also comparable (median 2(1, 3) vs. 2(2, 3) vs. 2(2, 3); p\u0026thinsp;=\u0026thinsp;0.3386) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB), indicating that initial follow-up timing had no effect on long-term medication requirements. Clinical symptom severity, assessed by the PMS, remained uniformly mild with no significant group differences (median 0(0, 2) vs. 2(0, 3) vs. 2(0, 3); p\u0026thinsp;=\u0026thinsp;0.2715) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC). ESR values were equivalent across the W4, W8, and W12 groups at the 6-month mark (p\u0026thinsp;=\u0026thinsp;0.933) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD), showing no group-specific differences in systemic inflammation. In contrast, hs-CRP levels at 24 weeks were significantly lower in the W4 group compared to both W8 and W12 groups ((median 0.7770(0.7770, 1.073) vs. 1.025(0.7770, 1.693) vs. 1.070(0.7770, 1.790); p\u0026thinsp;=\u0026thinsp;0.0453) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE\u003cb\u003e)\u003c/b\u003e, while W8 and W12 groups did not differ from each other, suggesting that earlier assessment may be associated with better long-term suppression of inflammatory activity. Mucosal healing, reflected by FOB negativity, showed no significant differences between groups (46.34% vs. 42.5% vs. 40.47%; p\u0026thinsp;=\u0026thinsp;0.8609) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eF\u003cb\u003e)\u003c/b\u003e. Taken together, these results indicate that despite differences in follow-up timing, 6-month clinical remission, endoscopic healing, inflammatory marker (except hs-CRP), and maintenance dose requirements were comparable across groups. Standard follow-up at 8 or 12 weeks was as effective as an early 4-week follow-up for long-term disease control in mild-to-moderate UC.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the timing of initial follow-up had a clear impact on the early course of mild-to-moderate UC. The W4 group showed an early, rapid decline in PMS by Week 4 and fewer patients with persistent or worsening symptoms through 3 months. This finding underscores the clinical value of early follow-up in achieving prompt symptomatic control. Current practice in mild UC often waits\u0026thinsp;~\u0026thinsp;12 weeks to evaluate response[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], but our data suggest this may leave some patients with unmitigated disease activity for too long. Our results make a compelling case for an initial assessment at 4 weeks to capture treatment non-responders and intensify therapy if needed.\u003c/p\u003e\u003cp\u003eBy Week 12, patients in the W4 group exhibited the highest rate of FOB negativity, which serves as a surrogate marker for mucosal healing[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], among the groups. However, this difference was not statistically significant. This trend is noteworthy given modern treat-to-target strategies emphasizing mucosal healing as a key endpoint. Endoscopic healing correlates with significantly improved long-term outcomes in UC[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Our findings imply that frequent early follow-up could promote mucosal healing, a vital element of long-term disease management.\u003c/p\u003e\u003cp\u003eA key advantage of the 4-week follow-up strategy was its ability to optimize 5-ASA therapy and minimize medication exposure without sacrificing disease control. The W4 group responded quickly to clinical improvement, allowing them to taper their doses early and achieve an 80% success rate of dose reduction within 3 months. Consequently, they maintained a lower overall 5-ASA dosage than the groups monitored later. Importantly, this decreased drug exposure did not lead to increased relapse or inflammation at 3 months, indicating that many patients could be safely de-escalated to maintenance doses sooner. This has practical implications for patient adherence and safety. Nearly half of UC patients express a desire to reduce their 5-ASA pill burden, and a high pill count is a known factor in non-adherence in UC[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Therefore, earlier dose reduction not only limits drug exposure and potential costs but may also enhance adherence and patient satisfaction with treatment.\u003c/p\u003e\u003cp\u003eDespite the differences observed in the early phase, by 24 weeks, all three follow-up strategies resulted in equivalent key outcomes in our mild-to-moderate UC patients. These findings suggest that standard follow-up at 8\u0026ndash;12 weeks is sufficient to eventually attain remission in mild UC under optimal therapy, which provides reassurance about the current standard practice. It also suggests that early follow-up mainly confers a temporal benefit, reducing disease burden sooner, rather than a categorical difference in whether remission is achieved. However, it is notable that the significantly lower CRP in the W4 group at 24 weeks hints that early intervention may confer a deeper, more durable remission[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This subtle biochemical advantage did not manifest in different clinical or endoscopic outcomes by 6 months, possibly due to the mild disease severity across all arms. Longer-term follow-up would be valuable to see if the initial CRP advantage in the W4 group translates to fewer relapses or complications over 1\u0026ndash;2 years.\u003c/p\u003e\u003cp\u003eImplementing a 4-week early follow-up strategy is not without challenges. Our findings revealed a subtle but essential consideration \u0026ndash; the potential for over-adjustment of therapy. In the W4 group (and to a lesser extent, the W8 group), inflammatory markers dropped rapidly by 8 weeks but exhibited a slight rebound by 12 weeks. If we reduce therapy at the first sign of improvement, we risk a \u0026ldquo;bounce-back\u0026rdquo; of disease activity. However, it emphasizes the importance of clear criteria and caution in early decision-making.\u003c/p\u003e\u003cp\u003eAn overlooked benefit of frequent early follow-up is improving patient\u0026ndash;physician communication and education. Beyond the pharmacologic adjustments made at the 4-week visit, the interaction may contribute to better outcomes[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Patients seen earlier have more opportunity to discuss their symptoms, medication usage, diet, and concerns, reinforcing treatment plans and building trust. By early check-in, we suspect patients in the W4 group received additional counseling on 5-ASA adherence, lifestyle, and what to expect in their disease course. This could partly explain their superior short-term symptom control, as engagement and understanding often translate into better self-management.\u003c/p\u003e\u003cp\u003eThe strengths of this study include: (1) Firstly, this work represents the first investigation to establish the optimal timing for 5-ASA efficacy assessment in patients with mild-to-moderate ulcerative colitis (UC), providing actionable guidance for treatment monitoring protocols. (2) Secondly, concurrently evaluating both short-term clinical symptom resolution (within 3 months) and 24-week long-term outcomes offers a comprehensive perspective on therapeutic durability. However, there are also several limitations to this study. (1) Firstly, its single-center design and relatively small patient cohort may restrict the generalizability of findings to broader clinical populations. (2) Secondly, dose adjustments relied heavily on physicians\u0026rsquo; clinical expertise, introducing potential variability in therapeutic decision-making that was not systematically quantified. (3) Thirdly, the inherent limitations of the observational design must be acknowledged. The most significant is the potential for confounding due to the non-randomized allocation to follow-up groups, despite the lack of significant baseline differences between groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Performance bias is possible as physicians and patients were not blinded to the follow-up schedule; however, the enhanced patient education in the 4-week group can be considered an integral benefit of the strategy itself. Attrition bias was mitigated as the proportion of patients lost to follow-up was comparable across groups. Furthermore, the use of objective biomarkers (hs-CRP, ESR) helps substantiate the findings from subjective clinical scores. However, our study included a well-characterized cohort of patients with mild-to-moderate UC, and the standard 5-ASA therapy employed is first-line treatment worldwide. Therefore, our findings remain applicable to other clinical environments. Future multi-center studies with larger, more diverse cohorts and standardized adjustment protocols are warranted to validate the generalizability of our conclusions.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe results of this study support a shift towards earlier initial follow-up for patients with mild-to-moderate UC starting 5-ASA therapy. Presently, some international guidelines consider a 3-month evaluation acceptable in mild disease. However, this study's results significantly benefit assessing patients as early as 4 weeks. These benefits include faster symptom relief, a trend toward quicker mucosal healing, reduced medication exposure through prompt dose adjustments, and an improved patient experience, all achieved without sacrificing long-term outcomes. This has direct clinical relevance: patients enjoy a better quality of life sooner, and clinicians can identify inadequate responders by one month, enabling earlier changes to alternative therapy if needed. Therefore, we recommend that mild-to-moderate UC patients be evaluated around 4 weeks after starting a new treatment, instead of the traditional 2\u0026ndash;3 months\u0026rsquo; timeframe, to confirm response or modify the treatment plan.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e5-ASA: 5-Aminosalicylic Acid\u003c/p\u003e\n\u003cp\u003eUC: Ulcerative Colitis\u003c/p\u003e\n\u003cp\u003ePMS: Partial Mayo Score\u003c/p\u003e\n\u003cp\u003ehs-CRP: High-sensitivity C-reactive Protein\u003c/p\u003e\n\u003cp\u003eESR: Erythrocyte Sedimentation Rate\u003c/p\u003e\n\u003cp\u003eFOB: Fecal Occult Blood\u003c/p\u003e\n\u003cp\u003eUCEIS: Ulcerative Colitis Endoscopic Index of Severity\u003c/p\u003e\n\u003cp\u003eRCT: Randomized Controlled Trial\u003c/p\u003e\n\u003cp\u003eECCO: European Crohn\u0026apos;s and Colitis Organization\u003c/p\u003e\n\u003cp\u003eSD: Standard Deviation\u003c/p\u003e\n\u003cp\u003eANOVA: Analysis of Variance\u003c/p\u003e\n\u003cp\u003eALT: Alanine Aminotransferase\u003c/p\u003e\n\u003cp\u003eAST: Aspartate Aminotransferase\u003c/p\u003e\n\u003cp\u003eTbil: Total Bilirubin\u003c/p\u003e\n\u003cp\u003eDbil: Direct Bilirubin\u003c/p\u003e\n\u003cp\u003eIbil: Indirect Bilirubin\u003c/p\u003e\n\u003cp\u003eALP: Alkaline Phosphatase\u003c/p\u003e\n\u003cp\u003eTP: Total Protein\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was conducted according to the guidelines of the Declaration of Helsinki, and proved by the Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University (reference number: KY20232344-F-1). Informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This work was supported by the following Independent Funds: the Natural Science Foundation of Shaanxi Province, Key Industrial Innovation Project Fund (2023-ZDLSF-44); the National Natural Science Foundation of China General Program (No. 82370588); National Natural Science Foundation of China Major Research Program Integration Project (No. 92259302); Independent Funds of the Key Laboratory (CBSKL2022ZZ34); The innovative medical research boosting project (XJZT25CX41); Special Project for Clinical New Technologies of Xijing Hospital (2024XJSY17).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003e(1) study concept and design: Y.D., F.W. and J.L.; Acquisition of data: Y.D., J.Z., T.Z., J.H. and Y.S.; Analysis and interpretation of data: Y.D., T.Z., X.L. and J.L.; (2) drafting and critical revision of the article for important intellectual content: Y.D., J.Z., T.W. and J.L.; All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLe Berre C, Honap S, Peyrin-Biroulet L. 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Br J Health Psychol. 2022;27:956\u0026ndash;70. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/bjhp.12584\u003c/span\u003e\u003cspan address=\"10.1111/bjhp.12584\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ulcerative colitis, 5-aminosalicylic acid, Follow-up timing","lastPublishedDoi":"10.21203/rs.3.rs-7873738/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7873738/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eFirst-line therapy for mild-to-moderate ulcerative colitis is 5-aminosalicylic acid. Optimal timing for the first evaluation after initiation remains unclear. Early follow-up may not reflect efficacy, while delayed assessment could be inefficient. We conducted a prospective observational cohort study to identify the optimal evaluation time after 5-aminosalicylic acid induction in newly diagnosed patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe cohort included 157 patients at Xijing Hospital. All received standard 5-aminosalicylic acid therapy, grouped by first follow-up timing: 4 weeks (W4; N\u0026thinsp;=\u0026thinsp;41), 8 weeks (W8; N\u0026thinsp;=\u0026thinsp;40), or 12 weeks (W12; N\u0026thinsp;=\u0026thinsp;42). Dose adjustments followed physician assessment. Primary outcome was clinical response/remission rate at Week 12 (Partial Mayo score). Secondary outcomes included inflammatory markers, mucosal healing, and dose adjustments.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAt Week 4, 68.29% of the W4 group achieved early clinical response. 82.93% in the W4 group reduced 5-aminosalicylic acid dosage by Week 4, versus 67.50% in the W8 group by Week 8. Consequently, cumulative 5-ASA exposure was lower in the W4 group. At Week 12, remission rates were similarly high across groups. At 24 weeks, long-term outcomes were comparable.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eFollow-up at 4 weeks enables timely dose optimization and reduced healthcare costs without compromising 6-month efficacy. Thus, 4 weeks may be optimal for first evaluation after starting 5-ASA in mild-to-moderate ulcerative colitis.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e\u003cp\u003eThis trial was retrospectively registered on ClinicalTrials.gov (NCT06998693) on May 6, 2025.\u003c/p\u003e","manuscriptTitle":"What is the Optimal Timing to Assess the Effect of 5-ASA in Patients with Mild-to- Moderate Ulcerative Colitis? A Single-Center Prospective Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 10:51:10","doi":"10.21203/rs.3.rs-7873738/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-11T07:38:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-17T05:21:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180587170332839588641944006782516036976","date":"2026-03-10T08:59:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182694145240990848500790636501078001735","date":"2025-12-22T07:19:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306372601146927296155601906910212041487","date":"2025-12-20T02:51:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T04:30:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165392191909563404063288413063693335581","date":"2025-12-08T02:26:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-07T17:30:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-07T04:57:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-06T11:25:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2025-11-04T17:19:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4a083c42-402b-4356-9b53-339fb47fd391","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-11T07:38:38+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-22T07:10:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-10 10:51:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7873738","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7873738","identity":"rs-7873738","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}