Efficacy and safety of upadacitinib, a selective JAK-1 inhibitor in treatment of ankylosing spondylitis: a meta-analysis

Efficacy and safety of upadacitinib, a selective JAK-1 inhibitor in treatment of ankylosing spondylitis: a meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy and safety of upadacitinib, a selective JAK-1 inhibitor in treatment of ankylosing spondylitis: a meta-analysis Qi Yao, Yixuan Zhu, Yanling Ma, Yanfang Pu, Xueting Yang, Zhiqing Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4760609/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2025 Read the published version in BMC Rheumatology → Version 1 posted 12 You are reading this latest preprint version Abstract Objective : To systemically evaluate efficacy and safety of upadacitinib (UPA), a selective inhibitor of Janus kinase 1 (JAK1) in treatment of ankylosing spondylitis (AS). Methods : PubMed, Embase, Elsevier, Springer, Google Scholar, Cochrane Library, China national knowledge infrastructure (CNKI), and other databases were used to retrieve literatures of randomized controlled trials (RCTs) of UPA treating AS until February 2024. After that, the data were extracted and the Revman 5.4 software was used to conduct a meta-analysis. Results : A total of 6 articles and 1653 patients (920 in an UPA group (15 mg, q.d) and 733 in a placebo group) were selected in this study. Respectively, the UPA treatment significantly increased numbers of the AS patients with 40%, 20%, and partial remission (PR) improvement in assessment of spondylo arthritis international society (ASAS) (ASAS 40: 95%CI: 2.41 - 4.3, p < 0.00001; ASAS 20: 95%CI: 2.12 - 3.62, p < 0.00001; ASAS PR: 95%CI: 2.81 - 7.48, p < 0.00001), Bath ankylosing spondylitis disease activity index (BASDAI50) (95%CI: 2.28 ～ 4.10, p < 0.00001), quality of life (95%CI: 2.06 ～ 3.17, p < 0.00001), AS disease activity score low disease activity (ASDAS LDA) (95%CI: 3.07～9.96, p < 0.00001), ASDAS inactive disease (ID) (95%CI: 2.03 ～ 17.22, p = 0.001), short-form 36 physical component summary (SF-36PCS) (95%CI: 1.53 ～2.81, p < 0.00001), and markedly reduced ASDAS C-reactive protein (CRP) (95%CI: -1.22 ～ -0.42, p < 0.0001), total back pain score (95%CI: -2.01 ～ -0.51, p = 0.001), nighttime back pain score (95%CI: -1.96 ～ -0.54, p = 0.0006), spondylo arthritis research consortium of Canada magnetic resonance imaging (SPARCC MRI) spine score (95%CI: -7.78 - -3.50, p < 0.00001) and SPARCC MRI sacroiliac joint score (95%CI: -5.99 - -3.09, p < 0.00001), Bath ankylosing spondylitis function index (BASFI) score (95%CI: -1.45 ～ -0.81, p < 0.00001), Maastricht ankylosing spondylitis enthesitis score (MASES) (95%CI: -2.34～-0.35, p = 0.008). Except for neutropenia (95%CI: 1.25 ～ 15.60, p = 0.02), no other obvious adverse effects (AEs) were found after the UPA treatment. Conclusions : UPA exerts a significant therapeutic effect in the patients with AS, and it has relative higher safety. Upadacitinib Ankylosing spondylitis Efficacy Safety Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Axial spinal arthritis (axSpA) is a chronic inflammatory rheumatic disease that mainly damages spine and sacroiliac joint [ 1 ]. AxSpA can be classified as non-imaging axial spondylitis (nr axSpA) and ankylosing spondylitis (AS) according to imaging manifestations and clinical symptoms [ 2 , 3 ]. AS, also known as spinal arthritis or serum negative spinal arthropathy, is mainly characterized by inflammation of the sacroiliac joints and spinal attachments, which belongs to category of rheumatism with unclear etiology. It affects sacroiliac joints, causing spinal rigidity and fibrosis, resulting in lesions in eye, lung, muscle, and bone at varying degrees. Usually, AS appears in early adulthood, and the morbidities of different ethnic groups are varied from 0.1–1.4% [ 4 ]. AS often invades the sacroiliac joints and then upwards to the cervical spine. In the early stage, inflammatory pain in the joints occurs accompanied by surrounding muscle spasms and stiffness which is noticeable in morning. Also, it manifests as nocturnal pain relieved by physical activity or taking painkillers. With the progression of this disease, spinal segments and joints are gradually deformed, leaving a limitation in physical movement function. In the late stage, entire spine and lower limbs are forward-flexing. Due to its debilitating nature, long-term and irreversibly structural damage, and a negative impact on quality of life, the therapeutic goal is to control symptoms and elevate health-related quality of life (HRQL). Currently, it is recommended to apply long-term pharmacological and non-pharmacological treatments in the therapy of AS [ 5 ]. According to recommendations of the American society of rheumatology (ACR) and the American association for spondylitis, the first-line treatment of AS is nonsteroidal anti-inflammatory drugs (NSAIDs). For those patients with poor responses to the NSAIDs, biologically modified anti-rheumatic drugs (bDMARDs) such as tumor necrosis factor-α (TNF-α) antagonist or interleukin-17 (IL-17) receptor inhibitor will be taken into consideration [ 6 ]. Although bDMARDs in combination with NSAIDs can achieve a good therapeutic effect and delay the progression of AS, the long-term use of these two drugs will affect normal functions of organs such as liver, kidney, and gastrointestinal tract. Further, only 40%ཞ50% of the patients achieve ASAS 40 [ 7 , 8 ]. Thus, it is necessary to search for a more effective and safer strategy for AS. Currently, Janus kinase (JAK) inhibitors are becoming a new alternative for autoimmune diseases. Compared with the bDMARDs, the JAK inhibitors will prevent inflammation spreading and transferring more thoroughly [ 9 ]. In addition, its oral administration has become another unique and convenient advantage compared to other biological agents [ 9 , 10 ]. The ASAS and the European league against rheumatism (EULAR) recommend to use the JAK inhibitors for patients with high disease activity after receiving routine treatments [ 11 ]. Nowadays, the updated recommendations suggest that the JAK inhibitors can be used as an alternative when bDMARDs have poor biological efficacy. UPA is an oral and reversible JAK inhibitor that has been applied in clinic to cure psoriatic arthritis, ulcerative colitis, Crohn's disease, and atopic dermatitis [ 12 – 15 ]. At present, it has been reported that UPA is effective and well tolerated in the active AS patients with poor responses to NSAIDs or bDMARDs [ 16 ]. Up to now, few studies have systematically assessed the efficacy and safety of UPA in AS. Therefore, a meta-analysis was conducted to explore the efficacy and safety of this reagent in AS. Materials and methods Search strategy This meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Databases including PubMed, Embase, Elsevier, Springer, Google Scholar, Cochrane Library, and CNKI were used to select eligible references from inception to February 2024. Search terms were listed as follows. (i) “upadacitinib” (title/abstract/keywords/Medical Subject Headings (MeSH)); (ii) “ankylosing spondylitis” (title/abstract/keywords/MeSH); (iii) “randomized controlled trial (RCT)” (title/abstract/keywords/MeSH); these search queries were combined using “AND”. The references were retrieved regardless of language of publication, study design, and publication type. Retrieved the databases to search for the RCT literatures on UPA treating AS until February 2024, using the keywords "upadacitinib" and "spondylitis ankylosing". A total of 209 studies were screened and then the duplicates were removed. After that, read titles and abstracts of these articles to exclud non-RCT, reviews, comments, meta-analysis, and articles that didn’t match this study. Data extract Two researchers independently reviewed the retrieved literatures before deciding whether to include. If consensus was reached, the literatures would be included; Once disagreements occurred, a third researcher would intervene and resolve through a panel discussion ultimately. The extracted data included author, year of publication, number of cases, gender, grouping, treatment and duration, indicators, and adverse reactions. Risk of bias assessment Cochrane Risk of Bias Assessment Tool was used to evaluate risks of biases which included random sequences generation (selection bias) and allocation concealment (selection bias), blinding (implementation bias), blind evaluation (measurement bias), data integrity (follow-up bias), selective reporting (reporting bias), and other biases. The assessments of risks of biases of the included literatures were classified as low, high, and unclear. Data presentation and statistical analysis The meta-analysis was conducted by using the Revman 5.4 software available at https://training.cochrane.org/online-learning/core-software/revman . The data were analyzed by relative ratio (OR) represented as 95% confidence interval (95% CI). A p value of less than 0.05 is thought to be significant. The heterogeneity was analyzed by Q-test using the I 2 statistic suggested by the Cochrane Collaboration. When the heterogeneity was low (I 2 0.05), a fixed effects model (FEM) is used for meta-analysis. Conversely, a random effects model (REM) is used (I 2 > 50%, p < 0.05) [ 17 ]. Results General information of included studies Initially, 209 relevant studies were retrieved. Imported them into the Note Express for deduplication test, and then 88 articles left. Read the titles and abstracts of the included studies carefully to exclude non-RCT, meta-analysis, review, comments, and cell or animal experiment. After that, 14 studies were read carefully to exclude those having no consistent outcome indicators or complete data. Finally, 6 studies [ 16 , 18 – 22 ] were included, all of which met the quality standards. The screening process for the literatures was displayed in Fig. 1 . A total of 920 patients were included in this study. The patients in the treatment group (460) and control groups (460) received oral UPA (15 mg, q.d) and placebo for the continuous 14 weeks, respectively. Three studies [ 16 , 20 , 21 ] reported indicators including ASAS 40, ASAS 20, ASAS PR, BASDAI50, ASDAS LDA, and ASDAS ID; Two studies [ 18 , 19 ] reported SF-36PCS and quality of life; Two studies [ 16 , 20 ] reported ASDAS CRP, total back pain, and nocturnal back pain; Two studies [ 16 , 22 ] reported SPARCC MRI; Three studies [ 16 , 20 , 22 ] reported MASES and BASFI. The general information of the included studies was shown in Table 1 , and detailed definitions of these indicators were shown in Table 2 . Table 1 General information of included studies Study Language Number Number of gender (Male/Female) Age (Years) Placebo UPA Placebo UPA Placebo UPA Victoria, 2023 English 209 211 158/51 153/58 42.2 ± 11.8 42.6 ± 12.4 Kiltz, 2023 English 157 156 63/94 67/89 42.5 ± 12.4 41.6 ± 12.0 Deodhar, 2022a English 157 156 63/94 67/89 42.5 ± 12.4 41.6 ± 12.0 van der Heijde, 2022 English 209 211 158/51 153/58 42.2 ± 11.8 42.6 ± 12.4 Deodhar, 2022b English 94 93 69/25 63/30 43.7 ± 12.1 47.0 ± 11.8 van der Heijde, 2019 English 94 93 69/25 63/30 43.7 ± 12.1 47.0 ± 11.8 Table 2 Details of tested indicators Indicator Detail ASAS Assessment of spondylo arthritis international society improvement of 40% (ASAS 40): improvement of at least 3 in 4 indices ≥ 40% and improvement score ≥ 2 (total score 10) or ≥ 20 (total score 100) ASAS 20: improvement of at least 3 in 4 indices ≥ 20% and improvement score ≥ 1 (total score 10) or ≥ 10 (total score 100) ASAS PR: improvement of all 4 indices ≤ 20% and improvement score ≤ 2 (total score 10) or ≤ 20 (total score 100) BASDAI50 Bath ankylosing spondylitis disease activity index improvement of 50% ASDAS LDA ASDAS low disease activity [C-reactive protein (CRP) < 2.1mg/L] ASDAS ID ASDAS inactive disease (CRP < 1.32mg/L) BASFI Bath ankylosing spondylitis function index MASES Maastricht ankylosing spondylitis enthesitis score SPARCC MRI Spondylo arthritis research consortium of Canada magnetic resonance imaging spine SPARCC MRI sacroiliac joint ASDAS CRP Ankylosing spondylitis disease activity score C-reactive protein Improvement of quality of life ASQOL: Ankylosing spondylitis quality of life inventory ASAS HI: ASAS health index SF-36PCS Physical component summary score of the short form 36 Note: ASAS 40, ASAS 20, ASAS PR, BASDAI50, Improvement of quality of life, ASDAS LDA, ASDAS ID, and SF-36PCS refer to numbers of the AS patients in the placebo and UPA groups (15 mg, q.d, 14 w) whom reach criteria of these indices; ASDAS CRP, total back pain, nighttime back pain, SPARCC MRI, BASFI, and MASES refer to difference values of these indices’ scores between the treatment (Placebo or UPA treatment at 14th week) and the baseline (Placebo or UPA treatment at 0 week). Risk of bias One study [ 19 ] had high risk of bias, which was associated with random sequence generation (selection bias). Also, it [ 19 ] has unclear risk of bias for incomplete outcome data (attrition bias). In addition, two studies [ 18 , 20 ] had unclear risk of bias due to random sequence generation (selection bias). Briefly, the risk percentage of each bias of the included studies was shown in Fig. 2 A, and the risk assessment for the single item bias of the studies was summarized in Fig. 2 B. UPA exerts a significant therapeutic effect on AS Three studies [ 16 , 20 , 21 ] reported ASAS40, ASAS20, and ASAS PR. A FEM was used to compare differences in numbers of the patients with ASAS 40 and ASAS 20 between the placebo and UPA groups (ASAS 40: p = 0.77, I 2 = 0%; ASAS 20: p = 0.87, I 2 = 0%). Correspondingly, a REM was used to test the difference in ASAS PR between the two groups ( p = 0.08, I 2 = 60%). It demonstrated that UPA significantly increased the numbers of the AS patients with ASAS 40, ASAS 20, and ASAS PR compared to the placebo (ASAS 40: OR = 3.22, 95%CI: 2.41–4.3, p < 0.00001; ASAS 20: OR = 2.77, 95%CI: 2.12–3.62, p < 0.00001; ASAS PR: OR = 4.58, 95%CI: 2.81–7.48, p < 0.00001), respectively. Further, no obvious risk of publication bias was found in these studies (Fig. 3 A). BASDAI50 was reported in the three studies [ 16 , 20 , 21 ]. The meta-analysis by a FEM (I 2 = 0%, p = 0.59) showed that the number of the AS patients with BASDAI50 in the UPA group was more than that in the control group (OR = 3.05, 95%CI: 2.28–4.10, p < 0.00001) (Fig. 3 B). Three studies [ 16 , 20 , 21 ] reported low disease activity (LDA) score and inactive disease (ID) score after the UPA (15mg, q.d) or placebo treatment for continuous 14 weeks. The meta-analysis by a REM (I 2 = 66%, p = 0.05) revealed that the numbers of the AS patients with LDA or ID in the UPA group were more than those in the placebo group (LDA: OR = 5.53, 95%CI: 3.07–9.96, p < 0.00001; ID: OR = 5.91, 95%CI: 2.03–17.22, p = 0.001), respectively (Fig. 3 C and 3 D). Two studies [ 16 , 20 ] evaluated ASDAS CRP prior to and post to the UPA or placebo treatment. The meta-analysis by a REM (I 2 = 86%, p = 0.008) indicated that UPA for the continuous 14 weeks significantly reduced ASDAS CRP compared to the placebo (Mean Difference = -0.82, 95% CI: -1.22 - -0.42, p < 0.0001) (Fig. 3 E). BASFI and MASES scores of the AS patients were reported in three studies [ 16 , 20 , 22 ]. The meta-analysis by a FEM (I 2 = 0%, p = 0.67) showed a significant difference in BASFI between the UPA treatment and placebo (Mean Difference = -1.13, 95% CI: -1.45 - -0.81, p < 0.00001) (Fig. 3 F). Similarly, the meta-analysis by a REM (I 2 =75%, p = 0.02) showed that UPA markedly reduced MASES score compared to the placebo (Mean Difference = -1.34, 95%CI: -2.34 - -0.35, p = 0.008) (Fig. 3 G). Two studies [ 16 , 20 ] reported improvement of total back pain score and nighttime back pain score after the UPA treatment. The analyses by the REMs (Total back pain: I 2 = 77%, p = 0.04; Nighttime back pain: I 2 ༝ 69%, p = 0.07) showed that UPA significantly improved the total back pain score (Mean Difference = -1.26, 95%CI: -2.01 - -0.51, p = 0.001) and nighttime back pain score (Mean Difference = -1.25, 95%CI: -1.96 - -0.54, p = 0.0006), respectively (Fig. 3 H and 3 I). SPARCC MRI spine and joint scores were evaluated by three studies [ 16 , 20 , 22 ]. The meta-analysis by a FEM (I 2 = 0%, p = 0.48) demonstrated that the UPA treatment significantly improved SPARCC MRI spine score (Mean Difference = -5.64, 95%CI: -7.78 - -3.50, p < 0.00001) and SPARCC MRI sacroiliac joint score (Mean Difference = -4.54, 95%CI: -5.99 - -3.09, p < 0.00001) compared to the placebo, respectively (Fig. 3 J). Meanwhile, no obvious risk of publication bias was present in these studies. Taken together, compared with the placebo, the UPA (15mg, q.d) treatment for the continuous 14 weeks significantly improved joint functions, reduced joint inflammation and disease activity, and delayed disease progress, which exerted a significant therapeutic effect on AS. UPA improves quality of life and health status of AS patients Two studies [ 18 , 19 ] reported UPA improved the AS patients’ quality of life and health status. The meta-analysis by a FEM (I 2 = 0%, p = 0.69) showed that UPA significantly increased ASQOL (OR = 2.62, 95%CI: 1.95–3.54, p < 0.00001) and ASAS HI (OR = 2.48, 95%CI: 1.81–3.38, p < 0.00001), respectively (Fig. 4 A). In addition, UPA markedly elevated SF-36PCS of the AS patients (I 2 ༝ 0%, p = 0.69, OR = 2.08, 95%CI: 1.53–2.81, p < 0.00001) (Fig. 4 B). No obvious risk of publication bias was found in these included studies. AEs of UPA in AS patients Three studies [ 16 , 20 , 22 ] reported AEs after the UPA treatment. Except for neutropenia (OR = 4.42, 95%CI: 1.25–15.60, p = 0.02), there were no significant differences in other AEs such as serious AE (OR = 2.79, 95%CI: 0.88–8.84, p = 0.08), serious infection (OR = 5.06, 95%CI: 0.87–29.36, p = 0.07), anemia (OR = 3.01, 95%CI: 0.47–19.23, p = 0.24), lymphocytopenia (OR = 0.49, 95%CI: 0.04–5.48, p = 0.56), hepatic disorder (OR = 1.69, 95%CI: 0.73–3.91, p = 0.22), and uveitis (OR = 0.71, 95%CI: 0.14–3.61, p = 0.68) between the UPA group and placebo group (Fig. 5 ). Discussion AS is a chronic inflammatory rheumatic disease affecting axial skeleton. Further, it seriously threatens lives and quality of life of patients. Thus, it is necessary to control symptoms of this disease, including preventing structural damage, and maintaining normal functions of bone and joint. Currently, NSAIDs, TNF-α antagonist and IL-17 receptor inhibitor are commonly used to cure AS. However, some patients still respond poorly to these reagents. In recent years, UPA, a specific JAK-1 inhibitor, has been selected as an alternative of NSAIDs or TNF-α antagonist or IL-17 receptor inhibitor when the efficacy isn’t satisfactory [ 23 ]. JAK is an intracellular enzyme transmitting membranous signals generated by interactions of cytokines or growth factor receptors. In this event, the JAKs phosphorylate and activate the signal transduction and signal transcription activating factors (STAT), which regulates intracellular gene expression and other activities. Correspondingly, UPA regulates this signaling at the JAKs’ sites, blocking the phosphorylation and activation of STAT. JAKs transmit cytokine signals through their own pairing including JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, and JAK2/TYK2. The inhibitory effects of UPA on JAK1 and JAK2 are stronger than JAK3 and TYK2. Furthermore, its inhibitory effect on JAK1 and JAK1/JAK3-mediated STAT phosphorylation is stronger than JAK2/JAK2-mediated. Until now, UPA has been approved to treat moderate to severe AD and RA, active psA and AS, moderate to severe UC. At present, few studies have systematically evaluated the efficacy and safety of UPA in treating AS. So, this meta-analysis was conducted to investigate the efficacy and safety of UPA in AS. A total of 6 articles and 1653 patients were included in accordance with the related inclusion and exclusion criteria. The meta-analysis showed that high heterogeneity occurred in some indices such as ASDAS CRP, ASDAS LDA, ASDAS ID, SF-36PCS, total back pain score, and nighttime back pain score in the included studies. So, a REM was used to assay these indices above. Also, positive comorbidity was observed in the presence of high I 2 , which was usually thought to be significant heterogeneities across studies. However, some argued that high I 2 didn’t always equate to high heterogeneity in meta-analysis of prevalence. It might be influenced by number of included studies and point estimation which couldn’t provide distribution information of overall parameters [ 24 ]. No significant heterogeneities were observed in ASAS, BASDAI50, quality of life, SPARCC MRI, BASFI, SF-36PCS, and adverse reactions (AEs). Further, the numbers of AS patients with ASAS 40 and BASDAI 50 respectively increased to 45% and 45% after the UPA treatment for the continuous 14 weeks. The BASFI score decreased by about 1.15 at 14th week. Compared with commonly anti-TNF-α therapy for AS, the BASDAI50 reached 52% at 6th month, and the BASFI decreased by 2.6 [ 25 ]. In addition, both spinal MRI inflammation score and sacroiliac joint MRI inflammation score significantly decreased after the UPA therapy. Based on SF-36PCS and quality of life scores, UPA significantly improved quality of life of the AS patients compared to the placebo. The meta-analysis of safety found that except for neutropenia, other AEs including severe AEs, severe infection, anemia, lymphopenia, hepatic disorder, uveitis were not statistically significant between UPA group and the placebo group. Therefore, neutropenia was thought to be one main AE of UPA. The treatment methods for neutropenia include removing cause of disease, symptomatic treatment, increasing neutrophil count with hematopoietic growth factors, and others. Conclusions In summary, UPA exerts a significant therapeutic effect on AS, and significantly improves quality of life of the patients. In addition, UPA has no obvious AEs and has higher safety in treating AS. Abbreviations ACR, American society of rheumatology AEs, adverse effects AS, ankylosing spondylitis ASAS, assessment of spondylo arthritis international society ASDAS, ankylosing spondylitis disease activity score axSpA, axial spinal arthritis BASFI, Bath ankylosing spondylitis function index bDMARDs, biologically modified anti-rheumatic drugs CNKI, China national knowledge infrastructure CRP, C-reactive protein EULAR, european league against rheumatism FEM, fixed effects model HRQL, health-related quality of life ID, inactive disease IL-17, interleukin-17 JAK, janus kinase LDA, low disease activity MASES, Maastricht ankylosing spondylitis enthesitis score NSAIDs, nonsteroidal anti-inflammatory drugs OR, relative ratio PR, partial remission PRISMA, preferred reporting items for systematic reviews and meta-analyses RCTs, randomized controlled trials REM, random effects model SF-36PCS, short-form 36 physical component summary SPARCC MRI, spondylo arthritis research consortium of Canada magnetic resonance imaging TYK, tyrosine kinase TNF-α, tumor necrosis factor-α UPA, upadacitinib Declarations Ethics approval and consent to participate Not applicable Consent for publication Not applicable Availability of data and material All data generated or analysed during this study are included in the uploaded supplementary material. Competing interests The authors declare that they have no competing interests. Funding This work was supported by grants from 2022 High-Level Talent Research Project of Yunnan Provincial Health Commission (2023-KHRCBZ-A02), and Open Projects for Construction Unit of Clinical Pharmacy Center of Yunnan Province (2023YJZX-YX11, 2023YJZX-YX15, 2023YJZX-YX24). Authors' contributions Qi Yao analyzed the data, and wrote the English version of this manuscript. Yixuan Zhu collected the data, performed meta-analysis, and wrote the Chinese version of this manuscript. Yanling Ma and Yanfang Pu collected the data of this study. Zhiqing Zhang and Xueting Yang designed this study. All authors reviewed the manuscript. References Navarro-Compán V, Sepriano A, El-Zorkany B, van der Heijde D. Axial spondyloarthritis. Ann Rheum Dis. 2021;80(12):1511–21. 10.1136/annrheumdis-2021-221035 . Baraliakos X, Braun J. 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Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2019;71(4):599–611. 10.1002/art.40753 . Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler LS, Fleishaker D, et al. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2021;80(8):1004–13. 10.1136/annrheumdis-2020-219601 . Navarro-Compán V, Wei JC, Van den Bosch F, Magrey M, Wang L, Fleishaker D, et al. Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebo-controlled trial. RMD Open. 2022;8(2):e002253. 10.1136/rmdopen-2022-002253 . 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J Allergy Clin Immunol. 2020;145(3):877–84. 10.1016/j.jaci.2019.11.025 . Danese S, Vermeire S, Zhou W, Pangan AL, Siffledeen J, Greenbloom S, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113–28. 10.1016/S0140-6736(22)00581-5 . van der Heijde D, Baraliakos X, Sieper J, Deodhar A, Inman RD, Kameda H, et al. Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial. Ann Rheum Dis. 2022;81(11):1515–23. 10.1136/ard-2022-222608 . Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. 10.1002/sim.1186 . Navarro-Compán V, Baraliakos X, Magrey M, Östör A, Saffore CD, Mittal M, et al. Effect of Upadacitinib on Disease Activity, Pain, Fatigue, Function, Health-Related Quality of Life and Work Productivity for Biologic Refractory Ankylosing Spondylitis. Rheumatol Ther. 2023;10(3):679–91. 10.1007/s40744-023-00536-2 . Kiltz U, Kishimoto M, Walsh JA, Sampaio-Barros P, Mittal M, Saffore CD, et al. Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2. Rheumatol Ther. 2023;10(4):887–99. 10.1007/s40744-023-00550-4 . Deodhar A, Van den Bosch F, Poddubnyy D, Maksymowych WP, van der Heijde D, Kim TH, et al. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400(10349):369–79. 10.1016/S0140-6736(22)01212-0 . Deodhar A, van der Heijde D, Sieper J, Van den Bosch F, Maksymowych WP, Kim TH, Kishimoto M, Ostor A, Combe B, Sui Y, Chu AD, Song IH. Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One-Year Results of a Double-Blind, Placebo-Controlled Study and Open-Label Extension. Arthritis Rheumatol. 2022;74(1):70–80. 10.1002 /art. van der Heijde D, Song IH, Pangan AL, Deodhar A, van den Bosch F, Maksymowych WP, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019;394(10214):2108–17. 10.1016/S0140-6736(19)32534-6 . Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018;2:23. 10.1186/s41927-018-0031-x . Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012; 2012(9): CD006829. 10.1002 /14651858. CD006829.pub2. Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL, et al. Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010;49(3):563–70. 10.1093 /rheumatology/kep422. Additional Declarations No competing interests reported. Supplementary Files Originaldatainpapers.xlsx Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 2025 Read the published version in BMC Rheumatology → Version 1 posted Editorial decision: Revision requested 22 Oct, 2024 Reviewers agreed at journal 26 Sep, 2024 Reviews received at journal 25 Sep, 2024 Reviewers agreed at journal 22 Sep, 2024 Reviews received at journal 31 Aug, 2024 Reviewers agreed at journal 10 Aug, 2024 Reviewers agreed at journal 08 Aug, 2024 Reviewers invited by journal 08 Aug, 2024 Editor invited by journal 06 Aug, 2024 Editor assigned by journal 29 Jul, 2024 Submission checks completed at journal 25 Jul, 2024 First submitted to journal 18 Jul, 2024 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4760609","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":343005093,"identity":"98db56d7-8cb1-4f9a-b577-0e80100e777b","order_by":0,"name":"Qi Yao","email":"","orcid":"","institution":"First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Yao","suffix":""},{"id":343005094,"identity":"0f934aeb-5a0f-4e0a-b9ec-a3eada643fbf","order_by":1,"name":"Yixuan Zhu","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Yixuan","middleName":"","lastName":"Zhu","suffix":""},{"id":343005095,"identity":"3854c735-4af2-43ec-9d6e-870edf4030f8","order_by":2,"name":"Yanling Ma","email":"","orcid":"","institution":"First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Yanling","middleName":"","lastName":"Ma","suffix":""},{"id":343005096,"identity":"c6eeae35-e96a-4821-a7c0-0d57136409e8","order_by":3,"name":"Yanfang Pu","email":"","orcid":"","institution":"First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Yanfang","middleName":"","lastName":"Pu","suffix":""},{"id":343005097,"identity":"aedfed8e-99ef-46fe-bf2a-bbc26aacedf8","order_by":4,"name":"Xueting Yang","email":"","orcid":"","institution":"First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Xueting","middleName":"","lastName":"Yang","suffix":""},{"id":343005098,"identity":"401c2c5b-f285-4310-ba21-6f5ea807b7fc","order_by":5,"name":"Zhiqing Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBAC+/aGxAcf/0nI8bM3EKnFgOfAY8MZbBbGkj0HiNUi4fhMmoOtInHDjQQitZhLMCdIM/BIMM6c+XjjDYYam2iCWixntyUYF0hIMPNLpxVbMBxLy20gqOfOmYTkGQYSbJKzc8wkGBsOE6HlRv6HwzwJEjwGN88QqcXgRkJiM88BCQmDGzxEagGGbTLjzAYJA8keoF8SiPELMAbTf3xsqKvvZz+88caHGhsi/ILsSIkEUpRDtJCqYxSMglEwCkYGAADJgkFtfWQTwQAAAABJRU5ErkJggg==","orcid":"","institution":"First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science \u0026 Technology","correspondingAuthor":true,"prefix":"","firstName":"Zhiqing","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-07-18 07:12:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4760609/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4760609/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41927-025-00467-1","type":"published","date":"2025-02-18T15:57:37+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63365006,"identity":"55f80fcc-53bc-4b83-9de7-bff3ae771895","added_by":"auto","created_at":"2024-08-27 11:05:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":95432,"visible":true,"origin":"","legend":"\u003cp\u003eLiterature screening and disposition\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/635ec9fc44febb08468bea4d.jpg"},{"id":63365005,"identity":"8ddecac0-c186-4f49-aa1d-c924625e1fe9","added_by":"auto","created_at":"2024-08-27 11:05:41","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":224229,"visible":true,"origin":"","legend":"\u003cp\u003eRisks of biases of included studies. A, Risk percentage of each bias in the studies; B, Summary of risks’ assessments of the studies\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/ab5f61e27d6f4a071c038d9a.jpg"},{"id":63367174,"identity":"5be64c67-5171-4ee2-8647-03e7bceb24da","added_by":"auto","created_at":"2024-08-27 11:29:41","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":422983,"visible":true,"origin":"","legend":"\u003cp\u003eEfficacy of UPA in AS patients. A, Number of AS patients with ASAS criteria in groups; B, Number of AS patientswith BASDAI50 in groups; C, Number of AS patients with ASDAS LDA in groups; D, Number of AS patients with ASDAS ID in groups; E, ASDAS CRP of AS patients before and after UPA or placebo treatment; F, BASFI score of AS patients before and after UPA or placebo treatment; G, MASES score of AS patients before and after UPA or placebo treatment; H, Total back pain score of AS patients before and after UPA or placebo treatment; I, Nighttime back pain score of AS patients before and after UPA or placebo treatment; J, SPARCC MRI score of AS patients before and after UPA or placebo treatment\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/3d5196d6cdf33aa5c06b0815.jpg"},{"id":63366509,"identity":"eb93dc5e-c77a-481e-8f2d-909f2b2acdc9","added_by":"auto","created_at":"2024-08-27 11:21:41","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":154137,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of UPA on quality of life and health status of AS patients. A, Effect of UPA on ASQOL and ASAS HI of AS patients; B, Effect of UPA on SF-36PCS of AS patients\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/21ef3538e6d77cd9df06f2c2.jpg"},{"id":63365756,"identity":"c53e9f28-0020-474d-975e-d242ea828388","added_by":"auto","created_at":"2024-08-27 11:13:41","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":271371,"visible":true,"origin":"","legend":"\u003cp\u003eAEs of UPA in AS patients\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/01e1db0656dfade371c1027c.jpg"},{"id":77054026,"identity":"41a150e5-8c6e-439c-967d-65ffb1a660a1","added_by":"auto","created_at":"2025-02-24 16:31:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1844807,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/4160c36c-3e77-4473-a249-4345d7b2e5f4.pdf"},{"id":63365010,"identity":"cc0a5a64-2d1f-4e7c-8316-b165b57c9b64","added_by":"auto","created_at":"2024-08-27 11:05:42","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":3237119,"visible":true,"origin":"","legend":"","description":"","filename":"Originaldatainpapers.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4760609/v1/fbb12b4978d0996d12d99f3c.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of upadacitinib, a selective JAK-1 inhibitor in treatment of ankylosing spondylitis: a meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAxial spinal arthritis (axSpA) is a chronic inflammatory rheumatic disease that mainly damages spine and sacroiliac joint [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. AxSpA can be classified as non-imaging axial spondylitis (nr axSpA) and ankylosing spondylitis (AS) according to imaging manifestations and clinical symptoms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. AS, also known as spinal arthritis or serum negative spinal arthropathy, is mainly characterized by inflammation of the sacroiliac joints and spinal attachments, which belongs to category of rheumatism with unclear etiology. It affects sacroiliac joints, causing spinal rigidity and fibrosis, resulting in lesions in eye, lung, muscle, and bone at varying degrees.\u003c/p\u003e \u003cp\u003eUsually, AS appears in early adulthood, and the morbidities of different ethnic groups are varied from 0.1\u0026ndash;1.4% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. AS often invades the sacroiliac joints and then upwards to the cervical spine. In the early stage, inflammatory pain in the joints occurs accompanied by surrounding muscle spasms and stiffness which is noticeable in morning. Also, it manifests as nocturnal pain relieved by physical activity or taking painkillers. With the progression of this disease, spinal segments and joints are gradually deformed, leaving a limitation in physical movement function. In the late stage, entire spine and lower limbs are forward-flexing. Due to its debilitating nature, long-term and irreversibly structural damage, and a negative impact on quality of life, the therapeutic goal is to control symptoms and elevate health-related quality of life (HRQL). Currently, it is recommended to apply long-term pharmacological and non-pharmacological treatments in the therapy of AS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to recommendations of the American society of rheumatology (ACR) and the American association for spondylitis, the first-line treatment of AS is nonsteroidal anti-inflammatory drugs (NSAIDs). For those patients with poor responses to the NSAIDs, biologically modified anti-rheumatic drugs (bDMARDs) such as tumor necrosis factor-α (TNF-α) antagonist or interleukin-17 (IL-17) receptor inhibitor will be taken into consideration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Although bDMARDs in combination with NSAIDs can achieve a good therapeutic effect and delay the progression of AS, the long-term use of these two drugs will affect normal functions of organs such as liver, kidney, and gastrointestinal tract. Further, only 40%ཞ50% of the patients achieve ASAS 40 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Thus, it is necessary to search for a more effective and safer strategy for AS.\u003c/p\u003e \u003cp\u003eCurrently, Janus kinase (JAK) inhibitors are becoming a new alternative for autoimmune diseases. Compared with the bDMARDs, the JAK inhibitors will prevent inflammation spreading and transferring more thoroughly [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In addition, its oral administration has become another unique and convenient advantage compared to other biological agents [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The ASAS and the European league against rheumatism (EULAR) recommend to use the JAK inhibitors for patients with high disease activity after receiving routine treatments [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Nowadays, the updated recommendations suggest that the JAK inhibitors can be used as an alternative when bDMARDs have poor biological efficacy.\u003c/p\u003e \u003cp\u003eUPA is an oral and reversible JAK inhibitor that has been applied in clinic to cure psoriatic arthritis, ulcerative colitis, Crohn's disease, and atopic dermatitis [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. At present, it has been reported that UPA is effective and well tolerated in the active AS patients with poor responses to NSAIDs or bDMARDs [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Up to now, few studies have systematically assessed the efficacy and safety of UPA in AS. Therefore, a meta-analysis was conducted to explore the efficacy and safety of this reagent in AS.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eSearch strategy\u003c/h2\u003e\n \u003cp\u003eThis meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Databases including PubMed, Embase, Elsevier, Springer, Google Scholar, Cochrane Library, and CNKI were used to select eligible references from inception to February 2024. Search terms were listed as follows.\u003c/p\u003e\u003cspan\u003e\n \u003cp\u003e(i) \u0026ldquo;upadacitinib\u0026rdquo; (title/abstract/keywords/Medical Subject Headings (MeSH));\u003c/p\u003e\n \u003c/span\u003e \u003cspan\u003e\n \u003cp\u003e(ii) \u0026ldquo;ankylosing spondylitis\u0026rdquo; (title/abstract/keywords/MeSH);\u003c/p\u003e\n \u003c/span\u003e \u003cspan\u003e\n \u003cp\u003e(iii) \u0026ldquo;randomized controlled trial (RCT)\u0026rdquo; (title/abstract/keywords/MeSH);\u003c/p\u003e\n \u003c/span\u003e \u003cspan\u003e\n \u003cp\u003ethese search queries were combined using \u0026ldquo;AND\u0026rdquo;. The references were retrieved regardless of language of publication, study design, and publication type.\u003c/p\u003e\n \u003c/span\u003e\n \u003cp\u003eRetrieved the databases to search for the RCT literatures on UPA treating AS until February 2024, using the keywords \u0026quot;upadacitinib\u0026quot; and \u0026quot;spondylitis ankylosing\u0026quot;. A total of 209 studies were screened and then the duplicates were removed. After that, read titles and abstracts of these articles to exclud non-RCT, reviews, comments, meta-analysis, and articles that didn\u0026rsquo;t match this study.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eData extract\u003c/h2\u003e\n \u003cp\u003eTwo researchers independently reviewed the retrieved literatures before deciding whether to include. If consensus was reached, the literatures would be included; Once disagreements occurred, a third researcher would intervene and resolve through a panel discussion ultimately.\u003c/p\u003e\n \u003cp\u003eThe extracted data included author, year of publication, number of cases, gender, grouping, treatment and duration, indicators, and adverse reactions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e\n \u003cp\u003eCochrane Risk of Bias Assessment Tool was used to evaluate risks of biases which included random sequences generation (selection bias) and allocation concealment (selection bias), blinding (implementation bias), blind evaluation (measurement bias), data integrity (follow-up bias), selective reporting (reporting bias), and other biases. The assessments of risks of biases of the included literatures were classified as low, high, and unclear.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eData presentation and statistical analysis\u003c/h2\u003e\n \u003cp\u003eThe meta-analysis was conducted by using the Revman 5.4 software available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://training.cochrane.org/online-learning/core-software/revman\u003c/span\u003e\u003c/span\u003e. The data were analyzed by relative ratio (OR) represented as 95% confidence interval (95% CI). A \u003cem\u003ep\u003c/em\u003e value of less than 0.05 is thought to be significant. The heterogeneity was analyzed by Q-test using the I\u003csup\u003e2\u003c/sup\u003e statistic suggested by the Cochrane Collaboration. When the heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026lt;\u0026thinsp;50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), a fixed effects model (FEM) is used for meta-analysis. Conversely, a random effects model (REM) is used (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGeneral information of included studies\u003c/h2\u003e \u003cp\u003eInitially, 209 relevant studies were retrieved. Imported them into the Note Express for deduplication test, and then 88 articles left. Read the titles and abstracts of the included studies carefully to exclude non-RCT, meta-analysis, review, comments, and cell or animal experiment. After that, 14 studies were read carefully to exclude those having no consistent outcome indicators or complete data. Finally, 6 studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] were included, all of which met the quality standards. The screening process for the literatures was displayed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA total of 920 patients were included in this study. The patients in the treatment group (460) and control groups (460) received oral UPA (15 mg, q.d) and placebo for the continuous 14 weeks, respectively. Three studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported indicators including ASAS 40, ASAS 20, ASAS PR, BASDAI50, ASDAS LDA, and ASDAS ID; Two studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] reported SF-36PCS and quality of life; Two studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] reported ASDAS CRP, total back pain, and nocturnal back pain; Two studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported SPARCC MRI; Three studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported MASES and BASFI. The general information of the included studies was shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and detailed definitions of these indicators were shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eGeneral information of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLanguage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNumber of gender (Male/Female)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eAge (Years)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUPA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVictoria, 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e158/51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKiltz, 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63/94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67/89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e41.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeodhar, 2022a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63/94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67/89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e41.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evan der Heijde, 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e158/51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeodhar, 2022b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e43.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e47.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evan der Heijde, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e43.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e47.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetails of tested indicators\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDetail\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAssessment of spondylo arthritis international society improvement of 40% (ASAS 40): improvement of at least 3 in 4 indices\u0026thinsp;\u0026ge;\u0026thinsp;40% and improvement score\u0026thinsp;\u0026ge;\u0026thinsp;2 (total score 10) or \u0026ge;\u0026thinsp;20 (total score 100)\u003c/p\u003e \u003cp\u003eASAS 20: improvement of at least 3 in 4 indices\u0026thinsp;\u0026ge;\u0026thinsp;20% and improvement score\u0026thinsp;\u0026ge;\u0026thinsp;1 (total score 10) or \u0026ge;\u0026thinsp;10 (total score 100)\u003c/p\u003e \u003cp\u003eASAS PR: improvement of all 4 indices\u0026thinsp;\u0026le;\u0026thinsp;20% and improvement score\u0026thinsp;\u0026le;\u0026thinsp;2 (total score 10) or \u0026le;\u0026thinsp;20 (total score 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBASDAI50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBath ankylosing spondylitis disease activity index improvement of 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASDAS LDA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASDAS low disease activity [C-reactive protein (CRP)\u0026thinsp;\u0026lt;\u0026thinsp;2.1mg/L]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASDAS ID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASDAS inactive disease (CRP\u0026thinsp;\u0026lt;\u0026thinsp;1.32mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBASFI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBath ankylosing spondylitis function index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMASES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMaastricht ankylosing spondylitis enthesitis score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPARCC MRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpondylo arthritis research consortium of Canada magnetic resonance imaging spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\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\u003eSPARCC MRI sacroiliac joint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASDAS CRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnkylosing spondylitis disease activity score C-reactive protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eImprovement of quality of life\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASQOL: Ankylosing spondylitis quality of life inventory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASAS HI: ASAS health index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSF-36PCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysical component summary score of the short form 36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNote: ASAS 40, ASAS 20, ASAS PR, BASDAI50, Improvement of quality of life, ASDAS LDA, ASDAS ID, and SF-36PCS refer to numbers of the AS patients in the placebo and UPA groups (15 mg, q.d, 14 w) whom reach criteria of these indices; ASDAS CRP, total back pain, nighttime back pain, SPARCC MRI, BASFI, and MASES refer to difference values of these indices\u0026rsquo; scores between the treatment (Placebo or UPA treatment at 14th week) and the baseline (Placebo or UPA treatment at 0 week).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias\u003c/h2\u003e \u003cp\u003eOne study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] had high risk of bias, which was associated with random sequence generation (selection bias). Also, it [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] has unclear risk of bias for incomplete outcome data (attrition bias). In addition, two studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] had unclear risk of bias due to random sequence generation (selection bias). Briefly, the risk percentage of each bias of the included studies was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, and the risk assessment for the single item bias of the studies was summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eUPA exerts a significant therapeutic effect on AS\u003c/h2\u003e \u003cp\u003eThree studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported ASAS40, ASAS20, and ASAS PR. A FEM was used to compare differences in numbers of the patients with ASAS 40 and ASAS 20 between the placebo and UPA groups (ASAS 40: \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.77, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%; ASAS 20: \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.87, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%). Correspondingly, a REM was used to test the difference in ASAS PR between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;60%). It demonstrated that UPA significantly increased the numbers of the AS patients with ASAS 40, ASAS 20, and ASAS PR compared to the placebo (ASAS 40: OR\u0026thinsp;=\u0026thinsp;3.22, 95%CI: 2.41\u0026ndash;4.3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001; ASAS 20: OR\u0026thinsp;=\u0026thinsp;2.77, 95%CI: 2.12\u0026ndash;3.62, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001; ASAS PR: OR\u0026thinsp;=\u0026thinsp;4.58, 95%CI: 2.81\u0026ndash;7.48, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), respectively. Further, no obvious risk of publication bias was found in these studies (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBASDAI50 was reported in the three studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The meta-analysis by a FEM (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.59) showed that the number of the AS patients with BASDAI50 in the UPA group was more than that in the control group (OR\u0026thinsp;=\u0026thinsp;3.05, 95%CI: 2.28\u0026ndash;4.10, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eThree studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported low disease activity (LDA) score and inactive disease (ID) score after the UPA (15mg, q.d) or placebo treatment for continuous 14 weeks. The meta-analysis by a REM (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;66%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05) revealed that the numbers of the AS patients with LDA or ID in the UPA group were more than those in the placebo group (LDA: OR\u0026thinsp;=\u0026thinsp;5.53, 95%CI: 3.07\u0026ndash;9.96, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001; ID: OR\u0026thinsp;=\u0026thinsp;5.91, 95%CI: 2.03\u0026ndash;17.22, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003eTwo studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] evaluated ASDAS CRP prior to and post to the UPA or placebo treatment. The meta-analysis by a REM (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;86%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) indicated that UPA for the continuous 14 weeks significantly reduced ASDAS CRP compared to the placebo (Mean Difference = -0.82, 95% CI: -1.22 - -0.42, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE).\u003c/p\u003e \u003cp\u003eBASFI and MASES scores of the AS patients were reported in three studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The meta-analysis by a FEM (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.67) showed a significant difference in BASFI between the UPA treatment and placebo (Mean Difference = -1.13, 95% CI: -1.45 - -0.81, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF). Similarly, the meta-analysis by a REM (I\u003csup\u003e2\u003c/sup\u003e =75%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) showed that UPA markedly reduced MASES score compared to the placebo (Mean Difference = -1.34, 95%CI: -2.34 - -0.35, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eG).\u003c/p\u003e \u003cp\u003eTwo studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] reported improvement of total back pain score and nighttime back pain score after the UPA treatment. The analyses by the REMs (Total back pain: I\u003csup\u003e2\u003c/sup\u003e = 77%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04; Nighttime back pain: I\u003csup\u003e2\u003c/sup\u003e ༝ 69%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07) showed that UPA significantly improved the total back pain score (Mean Difference = -1.26, 95%CI: -2.01 - -0.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and nighttime back pain score (Mean Difference = -1.25, 95%CI: -1.96 - -0.54, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eH and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eI).\u003c/p\u003e \u003cp\u003eSPARCC MRI spine and joint scores were evaluated by three studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The meta-analysis by a FEM (I\u003csup\u003e2\u003c/sup\u003e = 0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.48) demonstrated that the UPA treatment significantly improved SPARCC MRI spine score (Mean Difference = -5.64, 95%CI: -7.78 - -3.50, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) and SPARCC MRI sacroiliac joint score (Mean Difference = -4.54, 95%CI: -5.99 - -3.09, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) compared to the placebo, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eJ). Meanwhile, no obvious risk of publication bias was present in these studies.\u003c/p\u003e \u003cp\u003eTaken together, compared with the placebo, the UPA (15mg, q.d) treatment for the continuous 14 weeks significantly improved joint functions, reduced joint inflammation and disease activity, and delayed disease progress, which exerted a significant therapeutic effect on AS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eUPA improves quality of life and health status of AS patients\u003c/h2\u003e \u003cp\u003eTwo studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] reported UPA improved the AS patients\u0026rsquo; quality of life and health status. The meta-analysis by a FEM (I\u003csup\u003e2\u003c/sup\u003e = 0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69) showed that UPA significantly increased ASQOL (OR\u0026thinsp;=\u0026thinsp;2.62, 95%CI: 1.95\u0026ndash;3.54, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) and ASAS HI (OR\u0026thinsp;=\u0026thinsp;2.48, 95%CI: 1.81\u0026ndash;3.38, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). In addition, UPA markedly elevated SF-36PCS of the AS patients (I\u003csup\u003e2\u003c/sup\u003e ༝ 0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69, OR\u0026thinsp;=\u0026thinsp;2.08, 95%CI: 1.53\u0026ndash;2.81, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). No obvious risk of publication bias was found in these included studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAEs of UPA in AS patients\u003c/h2\u003e \u003cp\u003eThree studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported AEs after the UPA treatment. Except for neutropenia (OR\u0026thinsp;=\u0026thinsp;4.42, 95%CI: 1.25\u0026ndash;15.60, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), there were no significant differences in other AEs such as serious AE (OR\u0026thinsp;=\u0026thinsp;2.79, 95%CI: 0.88\u0026ndash;8.84, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08), serious infection (OR\u0026thinsp;=\u0026thinsp;5.06, 95%CI: 0.87\u0026ndash;29.36, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07), anemia (OR\u0026thinsp;=\u0026thinsp;3.01, 95%CI: 0.47\u0026ndash;19.23, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.24), lymphocytopenia (OR\u0026thinsp;=\u0026thinsp;0.49, 95%CI: 0.04\u0026ndash;5.48, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.56), hepatic disorder (OR\u0026thinsp;=\u0026thinsp;1.69, 95%CI: 0.73\u0026ndash;3.91, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.22), and uveitis (OR\u0026thinsp;=\u0026thinsp;0.71, 95%CI: 0.14\u0026ndash;3.61, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.68) between the UPA group and placebo group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAS is a chronic inflammatory rheumatic disease affecting axial skeleton. Further, it seriously threatens lives and quality of life of patients. Thus, it is necessary to control symptoms of this disease, including preventing structural damage, and maintaining normal functions of bone and joint. Currently, NSAIDs, TNF-α antagonist and IL-17 receptor inhibitor are commonly used to cure AS. However, some patients still respond poorly to these reagents.\u003c/p\u003e \u003cp\u003eIn recent years, UPA, a specific JAK-1 inhibitor, has been selected as an alternative of NSAIDs or TNF-α antagonist or IL-17 receptor inhibitor when the efficacy isn\u0026rsquo;t satisfactory [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. JAK is an intracellular enzyme transmitting membranous signals generated by interactions of cytokines or growth factor receptors. In this event, the JAKs phosphorylate and activate the signal transduction and signal transcription activating factors (STAT), which regulates intracellular gene expression and other activities. Correspondingly, UPA regulates this signaling at the JAKs\u0026rsquo; sites, blocking the phosphorylation and activation of STAT.\u003c/p\u003e \u003cp\u003eJAKs transmit cytokine signals through their own pairing including JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, and JAK2/TYK2. The inhibitory effects of UPA on JAK1 and JAK2 are stronger than JAK3 and TYK2. Furthermore, its inhibitory effect on JAK1 and JAK1/JAK3-mediated STAT phosphorylation is stronger than JAK2/JAK2-mediated.\u003c/p\u003e \u003cp\u003eUntil now, UPA has been approved to treat moderate to severe AD and RA, active psA and AS, moderate to severe UC. At present, few studies have systematically evaluated the efficacy and safety of UPA in treating AS. So, this meta-analysis was conducted to investigate the efficacy and safety of UPA in AS.\u003c/p\u003e \u003cp\u003eA total of 6 articles and 1653 patients were included in accordance with the related inclusion and exclusion criteria. The meta-analysis showed that high heterogeneity occurred in some indices such as ASDAS CRP, ASDAS LDA, ASDAS ID, SF-36PCS, total back pain score, and nighttime back pain score in the included studies. So, a REM was used to assay these indices above. Also, positive comorbidity was observed in the presence of high I\u003csup\u003e2\u003c/sup\u003e, which was usually thought to be significant heterogeneities across studies. However, some argued that high I\u003csup\u003e2\u003c/sup\u003e didn\u0026rsquo;t always equate to high heterogeneity in meta-analysis of prevalence. It might be influenced by number of included studies and point estimation which couldn\u0026rsquo;t provide distribution information of overall parameters [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNo significant heterogeneities were observed in ASAS, BASDAI50, quality of life, SPARCC MRI, BASFI, SF-36PCS, and adverse reactions (AEs). Further, the numbers of AS patients with ASAS 40 and BASDAI 50 respectively increased to 45% and 45% after the UPA treatment for the continuous 14 weeks. The BASFI score decreased by about 1.15 at 14th week. Compared with commonly anti-TNF-α therapy for AS, the BASDAI50 reached 52% at 6th month, and the BASFI decreased by 2.6 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In addition, both spinal MRI inflammation score and sacroiliac joint MRI inflammation score significantly decreased after the UPA therapy. Based on SF-36PCS and quality of life scores, UPA significantly improved quality of life of the AS patients compared to the placebo.\u003c/p\u003e \u003cp\u003eThe meta-analysis of safety found that except for neutropenia, other AEs including severe AEs, severe infection, anemia, lymphopenia, hepatic disorder, uveitis were not statistically significant between UPA group and the placebo group. Therefore, neutropenia was thought to be one main AE of UPA. The treatment methods for neutropenia include removing cause of disease, symptomatic treatment, increasing neutrophil count with hematopoietic growth factors, and others.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, UPA exerts a significant therapeutic effect on AS, and significantly improves quality of life of the patients. In addition, UPA has no obvious AEs and has higher safety in treating AS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACR, American society of rheumatology\u003c/p\u003e\n\u003cp\u003eAEs, adverse effects\u003c/p\u003e\n\u003cp\u003eAS, ankylosing spondylitis\u003c/p\u003e\n\u003cp\u003eASAS, assessment of spondylo arthritis international society\u003c/p\u003e\n\u003cp\u003eASDAS, ankylosing spondylitis\u0026nbsp;disease\u0026nbsp;activity\u0026nbsp;score\u003c/p\u003e\n\u003cp\u003eaxSpA, axial spinal arthritis\u003c/p\u003e\n\u003cp\u003eBASFI, Bath ankylosing spondylitis function index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ebDMARDs, biologically modified anti-rheumatic drugs\u003c/p\u003e\n\u003cp\u003eCNKI, China national knowledge infrastructure\u003c/p\u003e\n\u003cp\u003eCRP, C-reactive protein\u003c/p\u003e\n\u003cp\u003eEULAR, european league against rheumatism\u003c/p\u003e\n\u003cp\u003eFEM, fixed effects model\u003c/p\u003e\n\u003cp\u003eHRQL, health-related quality of life\u003c/p\u003e\n\u003cp\u003eID, inactive disease\u003c/p\u003e\n\u003cp\u003eIL-17, interleukin-17\u003c/p\u003e\n\u003cp\u003eJAK, janus kinase\u003c/p\u003e\n\u003cp\u003eLDA, low disease activity\u003c/p\u003e\n\u003cp\u003eMASES, Maastricht ankylosing spondylitis enthesitis score\u003c/p\u003e\n\u003cp\u003eNSAIDs, nonsteroidal anti-inflammatory drugs\u003c/p\u003e\n\u003cp\u003eOR, relative ratio\u003c/p\u003e\n\u003cp\u003ePR, partial remission\u003c/p\u003e\n\u003cp\u003ePRISMA, preferred reporting items for systematic reviews and meta-analyses\u003c/p\u003e\n\u003cp\u003eRCTs, randomized controlled trials\u003c/p\u003e\n\u003cp\u003eREM, random effects model\u003c/p\u003e\n\u003cp\u003eSF-36PCS, short-form 36 physical component summary\u003c/p\u003e\n\u003cp\u003eSPARCC MRI, spondylo arthritis research consortium of Canada magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eTYK, tyrosine kinase\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha;, tumor necrosis factor-\u0026alpha;\u003c/p\u003e\n\u003cp\u003eUPA, upadacitinib\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in the uploaded supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from 2022 High-Level Talent Research Project of Yunnan Provincial Health Commission (2023-KHRCBZ-A02), and Open Projects for Construction Unit of Clinical Pharmacy Center of Yunnan Province (2023YJZX-YX11, 2023YJZX-YX15, 2023YJZX-YX24).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eQi Yao \u0026nbsp;analyzed the data, and wrote the English version of this manuscript. 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BMC Rheumatol. 2018;2:23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s41927-018-0031-x\u003c/span\u003e\u003cspan address=\"10.1186/s41927-018-0031-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012; 2012(9): CD006829. 10.1002 /14651858. CD006829.pub2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL, et al. Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010;49(3):563\u0026ndash;70. 10.1093 /rheumatology/kep422.\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":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Upadacitinib, Ankylosing spondylitis, Efficacy, Safety, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-4760609/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4760609/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eObjective\u003c/em\u003e: To systemically evaluate efficacy and safety of upadacitinib (UPA), a selective inhibitor of Janus kinase 1 (JAK1) in treatment of ankylosing spondylitis (AS).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMethods\u003c/em\u003e: PubMed, Embase, Elsevier, Springer, Google Scholar, Cochrane Library, China national knowledge infrastructure (CNKI), and other databases were used to retrieve literatures of randomized controlled trials (RCTs) of UPA treating AS until February 2024. After that, the data were extracted and the Revman 5.4 software was used to conduct a meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults\u003c/em\u003e: A total of 6 articles and 1653 patients (920 in an UPA group (15 mg, q.d) and 733 in a placebo group) were selected in this study. Respectively, the UPA treatment significantly increased numbers of the AS patients with 40%, 20%, and partial remission (PR) improvement in assessment of spondylo arthritis international society (ASAS) (ASAS 40: 95%CI: 2.41 - 4.3, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.00001; ASAS 20: 95%CI: 2.12 - 3.62, \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.00001; ASAS PR: 95%CI: 2.81 - 7.48, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.00001), Bath ankylosing spondylitis disease activity index (BASDAI50) (95%CI: 2.28 ～ 4.10, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), quality of life (95%CI: 2.06 ～ 3.17, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), AS disease activity score low disease activity (ASDAS LDA) (95%CI: 3.07～9.96, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), ASDAS inactive disease (ID) (95%CI: 2.03 ～ 17.22, \u003cem\u003ep \u003c/em\u003e= 0.001), short-form 36 physical component summary (SF-36PCS) (95%CI: 1.53 ～2.81, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), and markedly reduced ASDAS C-reactive protein (CRP) (95%CI: -1.22 ～ -0.42, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.0001), total back pain score (95%CI: -2.01 ～ -0.51, \u003cem\u003ep \u003c/em\u003e= 0.001), nighttime back pain score (95%CI: -1.96 ～ -0.54, \u003cem\u003ep \u003c/em\u003e= 0.0006), spondylo arthritis research consortium of Canada magnetic resonance imaging (SPARCC MRI) spine score (95%CI: -7.78 - -3.50, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001) and SPARCC MRI sacroiliac joint score (95%CI: -5.99 - -3.09, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), Bath ankylosing spondylitis function index (BASFI) score (95%CI: -1.45 ～ -0.81, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.00001), Maastricht ankylosing spondylitis enthesitis score (MASES) (95%CI: -2.34～-0.35, \u003cem\u003ep \u003c/em\u003e= 0.008). Except for neutropenia (95%CI: 1.25 ～ 15.60, \u003cem\u003ep \u003c/em\u003e= 0.02), no other obvious adverse effects (AEs) were found after the UPA treatment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusions\u003c/em\u003e: UPA exerts a significant therapeutic effect in the patients with AS, and it has relative higher safety.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of upadacitinib, a selective JAK-1 inhibitor in treatment of ankylosing spondylitis: a meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-27 11:05:36","doi":"10.21203/rs.3.rs-4760609/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-22T16:31:47+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"12950257048778886212814618704308435348","date":"2024-09-26T09:34:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-25T16:32:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"119783110704864460310401219428812550273","date":"2024-09-22T15:19:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-31T07:30:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"268812103773742215658689872879143895491","date":"2024-08-10T18:20:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217963105308912391286848795507086115340","date":"2024-08-08T09:30:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-08T06:20:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-06T11:56:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-29T23:14:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-25T12:44:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Rheumatology","date":"2024-07-18T07:11:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f43b9245-bca7-4471-af0d-5ab0f6d79721","owner":[],"postedDate":"August 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-24T16:24:34+00:00","versionOfRecord":{"articleIdentity":"rs-4760609","link":"https://doi.org/10.1186/s41927-025-00467-1","journal":{"identity":"bmc-rheumatology","isVorOnly":false,"title":"BMC Rheumatology"},"publishedOn":"2025-02-18 15:57:37","publishedOnDateReadable":"February 18th, 2025"},"versionCreatedAt":"2024-08-27 11:05:36","video":"","vorDoi":"10.1186/s41927-025-00467-1","vorDoiUrl":"https://doi.org/10.1186/s41927-025-00467-1","workflowStages":[]},"version":"v1","identity":"rs-4760609","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4760609","identity":"rs-4760609","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}