Short-Term (24 Weeks) Treatment Efficacy and Safety of Ruxolitinib Cream in Participants with Vitiligo: A Systematic Review and Meta-Analysis

Short-Term (24 Weeks) Treatment Efficacy and Safety of Ruxolitinib Cream in Participants with Vitiligo: A Systematic Review and 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 Short-Term (24 Weeks) Treatment Efficacy and Safety of Ruxolitinib Cream in Participants with Vitiligo: A Systematic Review and Meta-Analysis Yuan Yuan, Li Zheng, Shaohua Yu, Xiaotong Gu, Hu Du, Yatong Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3171294/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Oct, 2024 Read the published version in Systematic Reviews → Version 1 posted 5 You are reading this latest preprint version Abstract Importance Vitiligo is a chronic skin disorder causing depigmentation. There is lack of evidence-based medical evidence regarding ruxolitinib efficacy and safety for Vitiligo. Objective To assess the efficacy and safety of ruxolitinib cream in treatment vitiligo. Methods The databases of PubMed, Embase, and Cochrane Library were searched. The literature screening was independently conducted by two reviewers. Data extraction and synthesis For continuous variables, weighted mean difference (WMD) along with a 95% confidence interval (CI) was performed. For dichotomous outcomes, we calculated the odds ratios (ORs) or risk ratios (RRs), and their corresponding 95% CIs. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Main outcomes and measures Symptoms, quality of life, and safety were evaluated using various measures, including the Facial Vitiligo Area Scoring Index (F-VASI), Total Vitiligo Area Scoring Index (T-VASI), Facial Body Surface Area (F-BAS), Total Body Surface Area (T-BAS) and Treatment-emergent Adverse Events (TEAEs). Results Three trials, involving a total of 830 participants from nine countries were included (female: 388, 46.7%, male: 442, 53.3%). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI75 (OR, 4.34 [95% CI, 2.67-7.06]; high), F-VASI50 (OR, 4.71 [95% CI, 3.24-6.84]; high), T-VASI75 (OR, 2.78 [95% CI, 1.10-7.00]; moderate), and T-VASI50 (OR, 4.47 [95% CI, 2.52-7.92]; high) when compared ruxolitinib to vehicle. Ruxolitinib were associated with more lowered percentage change of F-VASI scores (MD, –32.79 [95% CI, −36.37 to −29.21]; moderate), and T-VASI scores (MD, –20.22 [95% CI, −23.11 to −17.33]; moderate) from baseline compared to vehicle. There may not be a significant difference in the occurrence of TEAEs between ruxolitinib and vehicle (RR, 1.46 [95% CI, 0.85-2.49]; high). Conclusions The findings suggest that ruxolitinib cream holds promise as a treatment option for vitiligo. Further long-term studies are needed to assess its sustained efficacy and safety profile. Ruxolitinib Efficacy Safety Systematic review Meta-analysis Figures Figure 1 Figure 2 Figure 3 Key Points Question: Does ruxolitinib cream effectively and safely treat vitiligo? Finding s: Three trials, involving a total of 830 participants from nine countries were included (female: 388, 46.7%, male: 442, 53.3%) in this systematic review. High evidence showed that a significant increase in the likelihood of participants achieving F-VASI75 (OR=4.34, 95%CI:2.67-7.06), F-VASI50 (OR=4.71, 95%CI:3.24-6.84), T-VASI75 (OR=2.78, 95%CI:1.10-7.00), and T-VASI50 (OR=4.47, 95%CI:2.52-7.92) when compared ruxolitinib to vehicle. Meaning: This study found that ruxolitinib cream holds promise as a treatment option for vitiligo. 1 Introduction Vitiligo is a dermatological condition characterized by the selective loss of melanocytes, resulting in depigmented patches on the skin [ 1 , 2 ] . Its global prevalence is estimated to be around 0.5-2.0%, affecting individuals of all ages and skin types [ 3 – 6 ] . Despite its impact on quality of life, vitiligo is often underestimated as a cosmetic issue, overshadowing the significant psychological and social burden it imposes [ 7 , 8 ] . Recognized as an autoimmune disease, vitiligo has witnessed substantial advancements in treatment approaches [ 9 ] . Among the emerging therapeutic options, Janus kinase (JAK) inhibitors have demonstrated promising outcomes in managing vitiligo [ 10 ] . Ruxolitinib, a potent inhibitor of JAK1 and JAK2, has been investigated in several well-designed clinical trials, presenting evidence of its efficacy in vitiligo patients [ 11 , 12 ] . However, a comprehensive systematic review and meta-analysis examining the available evidence in this domain is lacking. Systematic reviews and meta-analyses play a pivotal role in evidence-based medical decision-making and the formulation of clinical guidelines [ 13 ] . Hence, the primary objective of this study is to assess the short-term (24 weeks) treatment efficacy and safety of ruxolitinib cream in individuals with vitiligo. 2 Methods 2.1 Review methods and registration The methodology of this systematic review and meta-analysis is based on the Cochrane Handbook [14] , and the reporting follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement [15] . The study has been registered on the PROSPERO (CRD42023431112). 2.2 Search strategy A comprehensive search strategy was employed to identify relevant studies for inclusion in this systematic review and meta-analysis. We conducted searches in three major English databases, namely PubMed, Embase, and Cochrane Library, to ensure comprehensive coverage of the literature. In addition, we extended our search to include two clinical trial registration platforms, namely the U.S. ClinicalTrials.gov (https://clinicaltrials.gov/) and the Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx). The search period spanned from the inception of these databases until April 20, 2023. To ensure the currency of our findings, we conducted an additional updated search to identify any recently published studies that may have emerged since the initial search. Furthermore, to minimize the risk of overlooking relevant studies, we meticulously examined the reference lists of relevant reviews and sought the latest pharmaceutical information in the field. 2.3 Eligibility criteria Prior to the literature screening process, we established specific eligibility criteria in consultation with clinical experts. The eligibility criteria were as follows: Participants: The study participants had to be diagnosed with vitiligo, with no restrictions on the type of vitiligo or characteristics such as gender, age, race, etc. Intervention: The intervention group must have received Ruxolitinib, a specific treatment under investigation. The control group, on the other hand, received the same treatment as the intervention group, except for the administration of ruxolitinib. Study Design: Only randomized controlled trials (RCTs) were considered eligible for inclusion. We did not impose any restrictions on the language of publication, ensuring that studies from various regions and in different languages were considered. 2.4 Study Selection The literature screening was independently conducted by two reviewers in the app of Covidence (https://app.covidence.org): First, screening based on titles and abstracts was performed, and conflicts were resolved through discussion. Next, the full texts of the studies included in the previous step were read for final screening, with involvement from a third party to resolve any disagreements. If two or more studies reported the outcomes of the same trial, we combined these studies into a single study. Conversely, if a single study reported the outcomes of two or more trials, we treated each of these trials as separate studies. 2.5 Data extraction Four reviewers divided into two groups participated in the data extraction process. The data extraction included basic information such as study title, authors, publication year, funding, sample size, and intervention details (name, dosage, and administration). We extracted the outcomes of included trials with separate for continuous outcomes and dichotomous outcomes. We created a data extraction table in Excel and conducted a pilot test before the formal data extraction. The pilot test ensured that all reviewers had a unified understanding of the extraction criteria and content. Only after achieving consensus among all reviewers, we proceeded with the formal data extraction. Data verification and cleaning were carried out by a third reviewers. This approach helps to minimize errors and maintain data quality throughout the process. 2.6 Outcomes Based on the guidance of clinical experts and considering the reported outcomes in the included studies, the following outcomes were assessed (For more detailed information about these outcomes and their descriptions, please see in supplemental table 1 ): 1. Symptoms: The assessment of symptoms involved measuring the percentage change from baseline using various scoring indexes, including F-VASI (Facial Vitiligo Area Scoring Index), T-VASI (Total Vitiligo Area Scoring Index), F-BAS (Facial Body Surface Area), and T-BAS (Total Body Surface Area). Additionally, dichotomous outcomes were considered, such as the percentage of participants achieving a ≥ 90% improvement from baseline in F-VASI (F-VASI90), the percentage of participants achieving a ≥ 75% improvement from baseline in F-VASI (F-VASI75), the percentage of participants achieving a ≥ 50% improvement from baseline in F-VASI (F-VASI50), the percentage of participants achieving a ≥ 25% improvement from baseline in F-VASI (F-VASI25), the percentage of participants achieving a ≥ 90% improvement from baseline in T-VASI (T-VASI90), the percentage of participants achieving a ≥ 75% improvement from baseline in T-VASI (T-VASI75), the percentage of participants achieving a ≥ 50% improvement from baseline in T-VASI (T-VASI50), the percentage of participants achieving a ≥ 25% improvement from baseline in T-VASI (T-VASI25), and the percentage of participants achieving a VNS (Vitiligo Noticeability Scale) score of 4 or 5 from baseline. 2. Quality of Life: The assessment of quality of life involved measuring the change from baseline using the Dermatology Life Quality Index (DLQI). 3. Safety: Safety outcomes included the evaluation of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuation due to Adverse Events (AEs). 2.7 Risk of ‑ bias assessment Two reviewers, working in pairs and independently, assessed each trials using a modified Cochrane risk of bias tool [16] . The assessment focused on five aspects, including rias arising from the randomization process, bias due to deviations from the intended intervention, bias due to missing outcome data (considered high risk of bias if ≥20% missing data), bias in measurement of the outcome, and bias in selection of the reported results. 2.8 Synthesis analysis We conducted the meta-analysis using R (version 4.2.0) software. The analysis for continuous variables was performed using the weighted mean difference (WMD) along with a 95% confidence interval (CI). For dichotomous outcomes of symptoms, we calculated the odds ratios (ORs) and their corresponding 95% CIs. For dichotomous outcomes of safety, we calculated the risk ratios (RRs) and their corresponding 95% CIs. To assess the heterogeneity of pooled effect estimates among the included studies, we employed both the chi-squared test and the I 2 statistic. A significance level of P < 0.05 and an I 2 value greater than 50% were considered as indicators of significant heterogeneity. In such cases, a random-effects model was applied. On the other hand, if there was no significant heterogeneity ( P ≥ 0.05, I 2 ≤ 50%), a fixed-effect model was used. Subgroup analyses and assessments of publication bias were conducted only when an adequate number of studies were included in the meta-analysis. This approach ensures that the subgroup analyses have sufficient statistical power and that the assessment of publication bias is reliable. 2.9 Assessing certainty of evidence The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework [17] . This framework categorizes evidence into four levels of certainty: high, moderate, low, or very low. For randomized controlled trials (RCTs), the initial rating for certainty starts at high, but it could be rated down based on limitations due to risk of bias [18] , imprecision [19] , inconsistency (heterogeneity) [20] , indirectness [21] , and publication bias [22] . 3 Results 3.1 Included studies A systematic search was conducted, resulting in the identification of 217 records from multiple databases. Additionally, 293 records were obtained from trial registration sources. After removing duplicate records and screening the titles and abstracts, a total of 117 records were excluded based on predetermined criteria. Subsequently, the full-text articles of the remaining records underwent a thorough assessment, ultimately leading to the inclusion of three trials reported in two studies for the meta-analysis ( Figure 1 ). 3.2 Study characteristics Three trials, involving a total of 830 participants with vitiligo from nine countries, were included in the analysis. Detailed inclusion and exclusion criteria for patient selection can be found in supplement table 2 . Table 1 and supplement table 3 provide a summary of the characteristics of the included trials. Of the participants, 388 (46.7%) were female, while 442 (53.3%) were male, with the mean age ranging from 38.9 to 48.3 years and the mean duration of vitiligo ranging from 9.7 to 15.9 years. Among the participants, 11 (1.3%) had segmental vitiligo, while the remaining 819 (98.7%) had non-segmental vitiligo. The treatment interventions included the use of vehicle and four different doses of topical ruxolitinib cream: 0.15% (once a day), 0.5% (once a day), 1.5% (once a day), and 1.5% (twice a day). 3.3 Risk of Bias Assessment The risk of bias assessment for each domain and the overall level can be found in supplement table 4 . Notably, for every outcome reported in the three trials, the risk of bias was determined to be "low." 3.4 Findings on Symptoms F-VASI90, F-VASI75, F-VASI50 and F-VASI25 Three trials, involving a total of 830 patients, were included in the meta-analysis to assess the effectiveness of ruxolitinib compared to vehicle by F-VASI90, F-VASI75, F-VASI50 and F-VASI25. The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI90 (OR, 9.61 [95% CI, 3.67-25.19]; I 2 = 0%; GRADE assessment: moderate certainty), F-VASI75 (OR, 4.34 [95% CI, 2.67-7.06]; I 2 = 0%; GRADE assessment: high certainty), F-VASI50 (OR, 4.71 [95% CI, 3.24-6.84]; I 2 = 0%; GRADE assessment: high certainty), and F-VASI25 (OR, 4.74 [95% CI, 3.28-6.86]; I 2 = 35%; GRADE assessment: high certainty) when compared ruxolitinib to vehicle ( Figure 2 ; Table 2 ). T-VASI90, T-VASI75, T-VASI50 and T-VASI25 Three trials, involving a total of 830 patients, were included in the meta-analysis to assess the effectiveness of ruxolitinib compared to vehicle by T-VASI90, T-VASI75, T-VASI50 and T-VASI25. The meta-analysis results demonstrated that the use of ruxolitinib did not significantly increase the likelihood of participants achieving T-VASI90 compared to vehicle (OR, 1.47 [95% CI, 0.24-9.09]; I 2 = 0%; GRADE assessment: moderate certainty). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving T-VASI75 (OR, 2.78 [95% CI, 1.10-7.00]; I 2 = 0%; GRADE assessment: moderate certainty), T-VASI50 (OR, 4.47 [95% CI, 2.52-7.92]; I 2 = 0%; GRADE assessment: high certainty), and T-VASI25 (OR, 3.45 [95% CI, 2.40-4.96]; I 2 = 3%; GRADE assessment: high certainty) when compared ruxolitinib to vehicle ( Figure 2 ; Table 2 ). VNS-4 or 5 The meta-analysis of two trials, involving a total of 673 patients, demonstrated that the use of ruxolitinib led to a higher proportion of participants achieving VNS-4 or 5 (OR, 6.15 [95% CI, 3.14-12.05]; I 2 = 0%; GRADE assessment: moderate certainty) in comparison to vehicle ( Figure 2 ; Table 2 ). F-VASI and T-VASI Three trials, which included 830 patients, reported the outcome of percentage change from baseline of F-VASI scores. The results showed that ruxolitinib were associated with more lowered percentage change of F-VASI scores from baseline (MD, –32.79 [95% CI, −36.37 to −29.21]; I 2 = 97%; GRADE assessment: moderate certainty) compared to vehicle. Three trials, which included 830 patients, reported the outcome of percentage change from baseline of T-VASI scores. The results showed that ruxolitinib were associated with more lowered percentage change of T-VASI scores from baseline (MD, –20.22 [95% CI, −23.11 to −17.33]; I 2 = 98%; GRADE assessment: moderate certainty) compared to vehicle ( Figure 3 ; Table 2 ). F-BSA and T-BSA Two trials, which included 673 patients, reported the outcome of percentage change from baseline of F-BSA scores. The results showed that ruxolitinib were associated with more lowered percentage change of F-BSA scores from baseline (MD, –19.40 [95% CI, −19.91 to −18.89]; I 2 = 0%; GRADE assessment: high certainty) compared to vehicle. Two trials, which included 673 patients, reported the outcome of percentage change from baseline of T-BSA scores. The results showed that ruxolitinib were associated with more lowered percentage change of T-BSA scores from baseline (MD, –10.50 [95% CI, −13.34 to −7.67]; I 2 = 99%; GRADE assessment: high certainty) compared to vehicle ( Figure 3 ; Table 2 ). 3.5 Findings on quality of life Two trials, which included 673 patients, reported the outcome of change from baseline of DLQI scores. The results showed that ruxolitinib were associated with more lowered change of DLQI scores from baseline (MD, –0.46 [95% CI, −0.73 to −0.19]; I 2 = 95%; GRADE assessment: moderate certainty) compared to vehicle ( Supplement figure 1 ; Table 2 ). 3.6 Findings on safety Three trials, which included 830 patients, reported these outcomes of TEAEs, SAEs and discontinuation due to AEs. The meta-analysis results indicated that there may not be a significant difference in the occurrence of TEAEs (RR, 1.46 [95% CI, 0.85-2.49]; I 2 = 53%; GRADE assessment: high certainty), SAEs (RR, 2.25 [95% CI, 0.59-8.67]; I 2 = 0%; GRADE assessment: moderate certainty), and discontinuation due to AEs (RR, 0.38 [95% CI, 0.10-1.48]; I 2 = 0%; GRADE assessment: high certainty) between ruxolitinib and vehicle ( supplement figure 5 ; Table 2 ). 3.7 Another analyses Subgroup analyses and assessments of publication bias were not conducted due to the limited number of clinical trials included in the analysis (only three trials) and the fact that all trials were conducted by the same research group, performing subgroup analyses and assessing publication bias may not be appropriate or informative. 4 Discussion In patients with vitiligo, we found moderate-certainly or high-certainly evidence that ruxolitinib cream improves clinical symptoms compared to vehicle cream, particularly in reducing facial vitiligo. Although there is moderate-quality evidence that ruxolitinib cream improves quality of life in vitiligo patients compared to vehicle cream, the observed mean decrease of 0.46 scores was not practically significant in relation to a total score of 30. Current evidence supports the safety of ruxolitinib as a topical treatment for vitiligo. This systematic review and meta-analysis have several notable strengths. These include a comprehensive search strategy to identify eligible trials, independent assessment of study selection, data extraction, and risk of bias by two reviewers, and the application of the GRADE approach to evaluate the certainty of evidence. Furthermore, the presentation of absolute effect measures enhances the interpretability of the findings, facilitating a more meaningful understanding of the clinical implications. Limitations of this systematic review and meta-analysis are as follows: 1) All three trials were conducted by the same research group introduces potential bias and may impact the reliability of the results, but this also reduces inherent heterogeneity among the trials; 2) Despite the inclusion of large sample sizes, the limited number of trials results in wider CIs for certain outcomes, which lowers the level of certainty in the evidence; 3) All participants were from Europe and America, so it remains to be determined whether the findings of our study are applicable to patients of Asian and African; 4) Due to the limited number of trials, subgroup analyses predefined by clinical experts, different doses of ruxolitinib, could not be done; 5) The fingdings of our study are based on short-term treatment (24 weeks) with ruxolitinib, and the long-term efficacy and safety of ruxolitinib are currently unknown. Future trials should ideally address these issues, and it is necessary to update this study timely. Vitiligo is categorized into three distinct forms based on the distribution of skin lesions: non-segmental, segmental, and mixed vitiligo [ 23 ] . Non-segmental vitiligo is the most common form. The symmetrical nature of the white patches is a distinguishing feature of non-segmental vitiligo, differentiating it from other forms of the condition [ 2 ] . Non-segmental vitiligo and segmental vitiligo are believed to have distinct pathogenetic mechanisms due to their differing clinical patterns. However, recent data suggest that there may be overlapping inflammatory mechanisms involved in both segmental and non-segmental vitiligo that contributing to the development of both subtypes [ 24 ] . In our study, the majority (98.7%) of the vitiligo cases included were non-segmental vitiligo. Therefore, clinicians should carefully consider the evidence provided by this study when making treatment decisions for different subtypes of vitiligo. Future trials should be conducted to specifically investigate the efficacy of ruxolitinib in each subtype of vitiligo that can gain a clearer understanding of the treatment's efficacy and applicability in diverse patient populations. Currently, there are many treatment options for vitiligo, and in many clinical situations, combination therapy needs to be considered [ 25 ] . The majority of participants included in our study had a history of prior therapy, including topical corticosteroids, calcineurin inhibitors, phototherapy and photochemotherapy, indicating that they were not first-episode patients. Indeed, the effectiveness of ruxolitinib specifically for first-episode vitiligo patients and the potential benefits of combining it with other treatments require further investigation [ 26 , 27 ] . Conducting future trials based on these hypotheses would provide valuable insights into the comparative efficacy of ruxolitinib in different patient populations and the potential synergistic effects of combination therapies that will contribute to advancing our understanding of the optimal treatment strategies for vitiligo. The skin plays a central role in various aspects of life. Many patients with vitiligo experience elevated levels of stress and often face social stigma due to their visible skin depigmentation [ 28 – 30 ] . In addition to the effectiveness of the treatment, various factors can contribute to the overall quality of life of patients with vitiligo, such as age at onset, extent, distribution, stigma, self-esteem and self-concept. Therefore, the lack of practically significant improvement observed in our study does not show that ruxolitinib is incapable of improving the quality of life in individuals with vitiligo. Indeed, the duration of treatment and the follow-up period can also significantly impact the assessment of quality of life outcomes in patients with vitiligo. The short-term nature of the treatment duration in the current study (24 weeks) may not have been sufficient to capture the full potential of ruxolitinib in improving quality of life. Additionally, long-term follow-up is necessary to evaluate the sustained effects of the treatment on patients' well-being over time. It is plausible that extended treatment duration and longer follow-up periods could yield different results and potentially demonstrate a positive impact of ruxolitinib on the quality of life of individuals with vitiligo. Similarly, the safety assessment of ruxolitinib in the treatment of vitiligo would benefit from studies with longer follow-up periods and larger sample sizes. To our knowledge, this systematic review and meta-analysis is the first to evaluate the efficacy and safety of ruxolitinib for patients with vitiligo. Unlike previous reviews [ 9 , 31 – 33 ] , our study has several distinct features. Firstly, it exclusively incorporates evidence from randomized controlled trials. Secondly, we employed the GRADE approach to evaluate the certainty of the evidence, providing a comprehensive and standardized assessment of the quality of the included studies. Lastly, to facilitate interpretation, we presented the absolute effects of ruxolitinib treatment. 5 Conclusion The results of our study provide compelling evidence for the efficacy of ruxolitinib in the short-term treatment of vitiligo. These findings indicate that ruxolitinib cream has the potential to be a promising treatment option for vitiligo. However, it is important to note that further study is necessary to evaluate the sustained efficacy and safety of ruxolitinib over a longer duration. Long-term and larger sample sizes studies are crucial in determining the prolonged effects and safety profile of ruxolitinib in the treatment of vitiligo. Declarations Acknowledgements None. Contributors YY, HD and YTZ planned and designed the study. YY and LZ developed search strategies. YY, LZ, SHY, and XTG screened potential studies and extracted data from the included studies. YY and LZ managed the data and performed the statistical analysis. HD conducted the arbitration under disagreement and ensured that there were no errors. HD and YTZ provided methodological support and helped to interpret findings. YY wrote the first draft. HD and YTZ revised the draft. All authors approved the final version of the manuscript. Funding None. Competing interests None declared. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not applicable. Ethics approval Not applicable. Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request from the corresponding author. References Ezzedine K, Eleftheriadou V, Whitton M, et al. Vitiligo. Lancet. 2015;386(9988):74-84. Bergqvist C, Ezzedine K. Vitiligo: A Review. Dermatology. 2020;236(6):571-592. Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206-1212. Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-491. Zhang Y, Cai Y, Shi M, et al. The Prevalence of Vitiligo: A Meta-Analysis. PLoS One. 2016;11(9): e0163806. Sehgal VN, Srivastava G. 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Spreading of pre-existing segmental vitiligo after immunotherapy with house dust mite in a patient with atopic dermatitis. Clin Exp Dermatol. 2015;40(8): 920-921. Eleftheriadou V, Atkar R, Batchelor J, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021. Br J Dermatol. 2022;186(1): 18-29. Speeckaert R, van Geel N. Vitiligo: An Update on Pathophysiology and Treatment Options. Am J Clin Dermatol. 2017;18(6): 733-744. Cunningham KN, Rosmarin D. Vitiligo Treatments: Review of Current Therapeutic Modalities and JAK Inhibitors. Am J Clin Dermatol. 2023;24(2): 165-186. Silverberg JI, Silverberg NB. Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 2013;149(2): 159-164. Wong SM, Baba R. Quality of life among Malaysian patients with vitiligo. Int J Dermatol. 2012;51(2): 158-161. Morrison B, Burden-Teh E, Batchelor JM, et al. Quality of life in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2017;177(6): e338-e339. Hwang JR, Driscoll MS. Review of Ruxolitinib for Treatment of Non-Segmental Vitiligo. Ann Pharmacother. 2022: 10600280221143748. Tavoletti G, Avallone G, Conforti C, et al. Topical ruxolitinib: A new treatment for vitiligo. J Eur Acad Dermatol Venereol. 2023; 0: 1-9. Smith P, Yao W, Shepard S, et al. Developing a JAK Inhibitor for Targeted Local Delivery: Ruxolitinib Cream. Pharmaceutics. 2021;13(7): 1044. Tables Table 1. List of included trials and baseline characteristics Study Country Sample sizes Proportion of males, % Proportion of females, % Age, mean (SD), y Intervention (sample sizes) Control (sample sizes) Duration of vitiligo, mean (SD), y Type of vitiligo F-VASI scores, mean (SD) F-BSA scores, mean (SD) Funding Rosmarin 2020 USA 157 73, 46.5% 84, 53.5% 48.3 (12.9) Topical Ruxolitinib cream (0.15%), qd, 24 weeks (31) Vehicle cream (32) 9.7 (6.6) Segmental (11), non-Segmental (146) 1.3 (0.8) 1.5 (0.9) Incyte Topical Ruxolitinib cream (0.50%), qd, 24 weeks (31) Topical Ruxolitinib cream (1.50%), qd, 24 weeks (30) Topical Ruxolitinib cream (1.50%), bid, 24 weeks (33) Rosmarin 2022 (TRuE-V1) USA, Canada, Bulgaria, France, Germany, Italy, the Netherlands, Poland, Spain 330 144, 43.6% 186, 56.3% 40.2 (15.9) Topical Ruxolitinib cream (1.50%), qd, 24 weeks (221) Vehicle cream (109) 13.6 (11.1) Segmental (0), non-Segmental (330) 1.0 (0.6) 1.1 (0.7) Incyte Rosmarin 2022 (TRuE-V2) USA, Canada, Bulgaria, France, Germany, Italy, the Netherlands, Poland, Spain 343 171, 49.9% 172, 50.1% 38.9 (14.3) Topical Ruxolitinib cream (1.50%), qd, 24 weeks (228) Vehicle cream (115) 15.9 (11.9) Segmental (0), non-Segmental (343) 0.9 (0.5) 1.0 (0.6) Incyte Table 2. GRADE summary of findings for ruxolitinib versus vehicle cream treatment for vitiligo Outcome Timeframe Study results and measurements Absolute effect estimates Certainty of the Evidence (Quality of evidence) Plain language summary Vehicle cream Ruxolitinib Cream Percentage of participants achieving F-VASI90 Odds ratio: 9.61 (CI 95% 3.67 - 25.19) Based on data from 830 participants in 3 studies Follow up 24 weeks 12 per 1000 105 per 1000 Moderate Due to serious imprecision 1 Ruxolitinib cream probably improves percentage of participants achieving F-VASI90 Difference: 93 more per 1000 (CI 95% 31 more - 222 more) Percentage of participants achieving F-VASI75 Odds ratio: 4.34 (CI 95% 2.67 - 7.06) Based on data from 30 participants in 3 studies Follow up 24 weeks 78 per 1000 269 per 1000 High Ruxolitinib cream improves percentage of participants achieving F-VASI75 Difference: 191 more per 1000 (CI 95% 106 more - 296 more) Percentage of participants achieving F-VASI50 Odds ratio: 4.71 (CI 95% 3.24 - 6.81) Based on data from 830 participants in 3 studies Follow up 24 weeks 164 per 1000 480 per 1000 High Ruxolitinib cream improves percentage of participants achieving F-VASI50 Difference: 316 more per 1000 (CI 95% 225 more - 408 more) Percentage of participants achieving F-VASI25 Odds ratio: 4.74 (CI 95% 3.28 - 6.86) Based on data from 830 participants in 3 studies Follow up 24 weeks 273 per 1000 640 per 1000 High Ruxolitinib cream improves percentage of participants achieving F-VASI25 Difference: 367 more per 1000 (CI 95% 279 more - 447 more) Percentage of participants achieving T-VASI90 Odds ratio: 1.47 (CI 95% 0.24 - 9.09) Based on data from 830 participants in 3 studies Follow up 24 weeks 6 per 1000 9 per 1000 Moderate Due to serious imprecision 1 Ruxolitinib cream probably improves percentage of participants achieving T-VASI90 Difference: 3 more per 1000 (CI 95% 5 fewer - 46 more) Percentage of participants achieving T-VASI75 Odds ratio: 2.78 (CI 95% 1.1 - 7.0) Based on data from 830 participants in 3 studies Follow up 24 weeks 16 per 1000 43 per 1000 Moderate Due to serious imprecision 1 Ruxolitinib cream probably improves percentage of participants achieving T-VASI75 Difference: 27 more per 1000 (CI 95% 2 more - 86 more) Percentage of participants achieving T-VASI50 Odds ratio: 4.47 (CI 95% 2.52 - 7.92) Based on data from 830 participants in 3 studies Follow up 24 weeks 51 per 1000 194 per 1000 High Ruxolitinib cream improves percentage of participants achieving T-VASI50 Difference: 143 more per 1000 (CI 95% 68 more - 248 more) Percentage of participants achieving T-VASI25 Odds ratio: 3.45 (CI 95% 2.4 - 4.96) Based on data from 830 participants in 3 studies Follow up 24 weeks 191 per 1000 449 per 1000 High Ruxolitinib cream improves percentage of participants achieving T-VASI25 Difference: 258 more per 1000 (CI 95% 171 more - 348 more) Percentage of participants achieving VNS4 or 5 Odds ratio: 6.15 (CI 95% 3.14 - 12.05) Based on data from 673 participants in 2 studies Follow up 24 weeks 40 per 1000 204 per 1000 Moderate Due to serious imprecision 1 Ruxolitinib cream probably improves percentage of participants achieving VNS4 or 5 Difference: 164 more per 1000 (CI 95% 76 more - 294 more) Treatment-related adverse events Relative risk: 1.46 (CI 95% 0.85 - 2.49) Based on data from 830 participants in 3 studies Follow up 24 weeks 109 per 1000 159 per 1000 High Ruxolitinib cream has little or no difference on treatment-related adverse events Difference: 50 more per 1000 (CI 95% 16 fewer - 162 more) Serious adverse events Relative risk: 2.25 (CI 95% 0.59 - 8.67) Based on data from 830 participants in 3 studies Follow up 24 weeks 4 per 1000 9 per 1000 Moderate Due to serious imprecision 1 Ruxolitinib cream probably has little or no difference on serious adverse events Difference: 5 more per 1000 (CI 95% 2 fewer - 31 more) Adverse events leading to discontinuation Relative risk: 0.38 (CI 95% 0.1 - 1.48) Based on data from 830 participants in 3 studies Follow up 24 weeks 12 per 1000 5 per 1000 High Ruxolitinib cream has more or no difference on adverse events leading to discontinuation Difference: 7 fewer per 1000 (CI 95% 11 fewer - 6 more) Percentage change from baseline F-VASI scores Measured by: Scale: - Lower better Based on data from 830 participants in 3 studies Follow up 24 weeks -15.8 Mean -48.59 Mean Moderate Due to serious inconsistency 2 Ruxolitinib cream probably decreases percentage change from baseline F-VASI scores Difference: MD 32.79 lower (CI 95% 36.37 lower - 29.21 lower) Percentage change from baseline T-VASI scores Measured by: Scale: - Lower better Based on data from 830 participants in 3 studies Follow up 24 weeks -8.99 Mean -29.21 Mean Moderate Due to serious inconsistency 3 Ruxolitinib cream probably decreases percentage change from baseline T-VASI scores Difference: MD 20.22 lower (CI 95% 23.11 lower - 17.33 lower) Percentage change from baseline F-BSA scores Measured by: Scale: - Lower better Based on data from 673 participants in 2 studies Follow up 24 weeks -8.25 Mean -27.65 Mean High Ruxolitinib cream decreases percentage change from baseline F-BSA scores Difference: MD 19.4 lower (CI 95% 19.91 lower - 18.89 lower) Percentage change from baseline T-BSA scores Measured by: Scale: - Lower better Based on data from 673 participants in 2 studies Follow up 24 weeks -3.15 Mean -13.65 Mean High Ruxolitinib cream decreases percentage change from baseline T-BSA scores Difference: MD 10.5 lower (CI 95% 13.34 lower - 7.67 lower) Change from baseline DLQI scores Measured by: Scale: - Lower better Based on data from 673 participants in 2 studies Follow up 24 weeks 0.72 Mean -1.18 Mean Moderate Due to serious inconsistency 4 Ruxolitinib cream probably decreases change from baseline DLQI scores slightly Difference: MD 0.46 lower (CI 95% 0.73 lower - 0.19 lower) 1. Rated down 1 level for serious imprecision due to wide confidence intervals; 2. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=97%); 3. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=98%); 4. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=95%). Supplementary Files Appendix.docx PRISMA2020checklist.docx Cite Share Download PDF Status: Published Journal Publication published 02 Oct, 2024 Read the published version in Systematic Reviews → Version 1 posted Editorial decision: Minor revision 16 Jul, 2024 Reviewers agreed at journal 02 Jul, 2024 Reviewers invited by journal 17 Mar, 2024 Editor assigned by journal 23 Jul, 2023 First submitted to journal 14 Jul, 2023 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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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yatong","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2023-07-14 17:34:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3171294/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3171294/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13643-024-02653-7","type":"published","date":"2024-10-02T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53006073,"identity":"95a2acf9-fa47-43e5-ae99-d4f32cd18dee","added_by":"auto","created_at":"2024-03-19 15:06:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":877111,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of article selection for the meta-analysis\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/54c914dcd446bb86f62d4ced.png"},{"id":53006075,"identity":"e9d8f5ba-1474-488b-887b-7fdd585d0d7d","added_by":"auto","created_at":"2024-03-19 15:06:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2181738,"visible":true,"origin":"","legend":"\u003cp\u003eRuxolitinib vs vehicle cream on F-VASI90, F-VASI75, F-VASI50, F-VASI25, T-VASI90, T-VASI75, T-VASI50, T-VASI25 and VNS-4 or 5\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/63c58bd02e02c3e54656915a.png"},{"id":53006071,"identity":"ca7e111a-8f7f-4756-b720-d52506964dea","added_by":"auto","created_at":"2024-03-19 15:06:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":872466,"visible":true,"origin":"","legend":"\u003cp\u003eRuxolitinib vs vehicle cream on F-VASI, T-VASI, F-BSA and T-BSA\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/96e9682d09eb8f5f411a509c.png"},{"id":66096939,"identity":"24e77cff-f4b8-4884-b4b9-a6280bb7162e","added_by":"auto","created_at":"2024-10-07 16:11:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4691297,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/670d4d1f-519c-417a-9141-27a9bef428e1.pdf"},{"id":53006074,"identity":"c38e8479-57ac-49c4-90e1-065bce3604cd","added_by":"auto","created_at":"2024-03-19 15:06:07","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":3130605,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/e9139bfae07afdc454017192.docx"},{"id":53006069,"identity":"a55d4888-ef4b-449c-b90f-61377eaf5d8c","added_by":"auto","created_at":"2024-03-19 15:06:05","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":31958,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMA2020checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-3171294/v1/540d225373df356e45802a24.docx"}],"financialInterests":"","formattedTitle":"Short-Term (24 Weeks) Treatment Efficacy and Safety of Ruxolitinib Cream in Participants with Vitiligo: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Key Points","content":"\u003cp\u003e\u003cstrong\u003eQuestion:\u0026nbsp;\u003c/strong\u003eDoes ruxolitinib cream effectively and safely treat vitiligo?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinding\u003c/strong\u003e\u003cstrong\u003es:\u003c/strong\u003e Three trials, involving a total of 830 participants from nine countries were included (female: 388, 46.7%, male: 442, 53.3%) in this systematic review. High evidence showed that a significant increase in the likelihood of participants achieving F-VASI75 (OR=4.34, 95%CI:2.67-7.06), F-VASI50 (OR=4.71, 95%CI:3.24-6.84), T-VASI75\u0026nbsp;(OR=2.78, 95%CI:1.10-7.00), and\u0026nbsp;T-VASI50\u0026nbsp;(OR=4.47, 95%CI:2.52-7.92) when compared ruxolitinib to vehicle.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeaning:\u0026nbsp;\u003c/strong\u003eThis study found that ruxolitinib cream holds promise as a treatment option for vitiligo.\u003c/p\u003e"},{"header":"1 Introduction","content":"\u003cp\u003eVitiligo is a dermatological condition characterized by the selective loss of melanocytes, resulting in depigmented patches on the skin \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Its global prevalence is estimated to be around 0.5-2.0%, affecting individuals of all ages and skin types \u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Despite its impact on quality of life, vitiligo is often underestimated as a cosmetic issue, overshadowing the significant psychological and social burden it imposes \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Recognized as an autoimmune disease, vitiligo has witnessed substantial advancements in treatment approaches \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong the emerging therapeutic options, Janus kinase (JAK) inhibitors have demonstrated promising outcomes in managing vitiligo \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Ruxolitinib, a potent inhibitor of JAK1 and JAK2, has been investigated in several well-designed clinical trials, presenting evidence of its efficacy in vitiligo patients \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. However, a comprehensive systematic review and meta-analysis examining the available evidence in this domain is lacking. Systematic reviews and meta-analyses play a pivotal role in evidence-based medical decision-making and the formulation of clinical guidelines \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Hence, the primary objective of this study is to assess the short-term (24 weeks) treatment efficacy and safety of ruxolitinib cream in individuals with vitiligo.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Review methods and registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe methodology of this systematic review and meta-analysis is based on the Cochrane Handbook \u003csup\u003e[14]\u003c/sup\u003e, and the reporting follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement \u003csup\u003e[15]\u003c/sup\u003e. The study has been registered on the PROSPERO (CRD42023431112).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Search strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comprehensive search strategy was employed to identify relevant studies for inclusion in this systematic review and meta-analysis. We conducted searches in three major English databases, namely PubMed, Embase, and Cochrane Library, to ensure comprehensive coverage of the literature. In addition, we extended our search to include two clinical trial registration platforms, namely the U.S. ClinicalTrials.gov (https://clinicaltrials.gov/) and the Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx). The search period spanned from the inception of these databases until April 20, 2023.\u003c/p\u003e\n\u003cp\u003eTo ensure the currency of our findings, we conducted an additional updated search to identify any recently published studies that may have emerged since the initial search. Furthermore, to minimize the risk of overlooking relevant studies, we meticulously examined the reference lists of relevant reviews and sought the latest pharmaceutical information in the field.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Eligibility criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior to the literature screening process, we established specific eligibility criteria in consultation with clinical experts. The eligibility criteria were as follows:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eParticipants:\u003c/em\u003e\u003c/strong\u003e The study participants had to be diagnosed with vitiligo, with no restrictions on the type of vitiligo or characteristics such as gender, age, race, etc. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIntervention:\u003c/em\u003e\u003c/strong\u003e The intervention group must have received Ruxolitinib, a specific treatment under investigation. The control group, on the other hand, received the same treatment as the intervention group, except for the administration of ruxolitinib. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Design:\u003c/em\u003e\u003c/strong\u003e Only randomized controlled trials (RCTs) were considered eligible for inclusion. \u003c/p\u003e\n\u003cp\u003eWe did not impose any restrictions on the language of publication, ensuring that studies from various regions and in different languages were considered.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Study Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe literature screening was independently conducted by two reviewers in the app of Covidence (https://app.covidence.org): First, screening based on titles and abstracts was performed, and conflicts were resolved through discussion. Next, the full texts of the studies included in the previous step were read for final screening, with involvement from a third party to resolve any disagreements. If two or more studies reported the outcomes of the same trial, we combined these studies into a single study. Conversely, if a single study reported the outcomes of two or more trials, we treated each of these trials as separate studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Data extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFour reviewers divided into two groups participated in the data extraction process. The data extraction included basic information such as study title, authors, publication year, funding, sample size, and intervention details (name, dosage, and administration). We extracted the outcomes of included trials with separate for continuous outcomes and dichotomous outcomes. We created a data extraction table in Excel and conducted a pilot test before the formal data extraction. The pilot test ensured that all reviewers had a unified understanding of the extraction criteria and content. Only after achieving consensus among all reviewers, we proceeded with the formal data extraction. Data verification and cleaning were carried out by a third reviewers. This approach helps to minimize errors and maintain data quality throughout the process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6 Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on the guidance of clinical experts and considering the reported outcomes in the included studies, the following outcomes were assessed (For more detailed information about these outcomes and their descriptions, please see in \u003cstrong\u003esupplemental table 1\u003c/strong\u003e):\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e1. Symptoms:\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eThe assessment of symptoms involved measuring the percentage change from baseline using various scoring indexes, including F-VASI (Facial Vitiligo Area Scoring Index), T-VASI (Total Vitiligo Area Scoring Index), F-BAS (Facial Body Surface Area), and T-BAS (Total Body Surface Area). Additionally, dichotomous outcomes were considered, such as the percentage of participants achieving a \u0026ge; 90% improvement from baseline in F-VASI (F-VASI90), the percentage of participants achieving a \u0026ge; 75% improvement from baseline in F-VASI (F-VASI75), the percentage of participants achieving a \u0026ge; 50% improvement from baseline in F-VASI (F-VASI50), the percentage of participants achieving a \u0026ge; 25% improvement from baseline in F-VASI (F-VASI25), the percentage of participants achieving a \u0026ge; 90% improvement from baseline in T-VASI (T-VASI90), the percentage of participants achieving a \u0026ge; 75% improvement from baseline in T-VASI (T-VASI75), the percentage of participants achieving a \u0026ge; 50% improvement from baseline in T-VASI (T-VASI50), the percentage of participants achieving a \u0026ge; 25% improvement from baseline in T-VASI (T-VASI25), and the percentage of participants achieving a VNS (Vitiligo Noticeability Scale) score of 4 or 5 from baseline.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2. Quality of Life:\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eThe assessment of quality of life involved measuring the change from baseline using the Dermatology Life Quality Index (DLQI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3. Safety:\u003c/em\u003e\u003c/strong\u003e Safety outcomes included the evaluation of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuation due to Adverse Events (AEs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.7 Risk\u003c/strong\u003e\u003cstrong\u003eof\u003c/strong\u003e\u003cstrong\u003e‑\u003c/strong\u003e\u003cstrong\u003ebias assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo reviewers, working in pairs and independently, assessed each trials using a modified Cochrane risk of bias tool \u003csup\u003e[16]\u003c/sup\u003e. The assessment focused on five aspects, including rias arising from the randomization process, bias due to deviations from the intended intervention, bias due to missing outcome data (considered high risk of bias if \u0026ge;20% missing data), bias in measurement of the outcome, and bias in selection of the reported results. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 Synthesis analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted the meta-analysis using R (version 4.2.0) software. The analysis for continuous variables was performed using the weighted mean difference (WMD) along with a 95% confidence interval (CI). For dichotomous outcomes of symptoms, we calculated the odds ratios (ORs) and their corresponding 95% CIs. For dichotomous outcomes of safety, we calculated the risk ratios (RRs) and their corresponding 95% CIs. To assess the heterogeneity of pooled effect estimates among the included studies, we employed both the chi-squared test and the I\u003csup\u003e2\u003c/sup\u003e statistic. A significance level of \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05 and an I\u003csup\u003e2\u003c/sup\u003e value greater than 50% were considered as indicators of significant heterogeneity. In such cases, a random-effects model was applied. On the other hand, if there was no significant heterogeneity (\u003cem\u003eP \u003c/em\u003e\u0026ge; 0.05, I\u003csup\u003e2\u003c/sup\u003e \u0026le; 50%), a fixed-effect model was used. Subgroup analyses and assessments of publication bias were conducted only when an adequate number of studies were included in the meta-analysis. This approach ensures that the subgroup analyses have sufficient statistical power and that the assessment of publication bias is reliable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.9 Assessing certainty of evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework \u003csup\u003e[17]\u003c/sup\u003e. This framework categorizes evidence into four levels of certainty: high, moderate, low, or very low. For randomized controlled trials (RCTs), the initial rating for certainty starts at high, but it could be rated down based on limitations due to risk of bias \u003csup\u003e[18]\u003c/sup\u003e, imprecision \u003csup\u003e[19]\u003c/sup\u003e, inconsistency (heterogeneity) \u003csup\u003e[20]\u003c/sup\u003e, indirectness \u003csup\u003e[21]\u003c/sup\u003e, and publication bias \u003csup\u003e[22]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Included studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA systematic search was conducted, resulting in the identification of 217 records from multiple databases. Additionally, 293 records were obtained from trial registration sources. After removing duplicate records and screening the titles and abstracts, a total of 117 records were excluded based on predetermined criteria. Subsequently, the full-text articles of the remaining records underwent a thorough assessment, ultimately leading to the inclusion of three trials reported in two studies for the meta-analysis (\u003cstrong\u003eFigure 1\u003c/strong\u003e). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Study characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, involving a total of 830 participants with vitiligo from nine countries, were included in the analysis. Detailed inclusion and exclusion criteria for patient selection can be found in \u003cstrong\u003esupplement table 2\u003c/strong\u003e. \u003cstrong\u003eTable 1\u003c/strong\u003e and \u003cstrong\u003esupplement table 3\u003c/strong\u003e provide a summary of the characteristics of the included trials. Of the participants, 388 (46.7%) were female, while 442 (53.3%) were male, with the mean age ranging from 38.9 to 48.3 years and the mean duration of vitiligo ranging from 9.7 to 15.9 years. Among the participants, 11 (1.3%) had segmental vitiligo, while the remaining 819 (98.7%) had non-segmental vitiligo. The treatment interventions included the use of vehicle and four different doses of topical ruxolitinib cream: 0.15% (once a day), 0.5% (once a day), 1.5% (once a day), and 1.5% (twice a day).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Risk of Bias Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe risk of bias assessment for each domain and the overall level can be found in \u003cstrong\u003esupplement table 4\u003c/strong\u003e. Notably, for every outcome reported in the three trials, the risk of bias was determined to be \u0026quot;low.\u0026quot;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Findings on Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eF-VASI90, F-VASI75, F-VASI50 and F-VASI25\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, involving a total of 830 patients, were included in the meta-analysis to assess the effectiveness of ruxolitinib compared to vehicle by F-VASI90, F-VASI75, F-VASI50 and F-VASI25. The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI90 (OR, 9.61 [95% CI, 3.67-25.19]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: moderate certainty), F-VASI75 (OR, 4.34 [95% CI, 2.67-7.06]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: high certainty), F-VASI50 (OR, 4.71 [95% CI, 3.24-6.84]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: high certainty), and F-VASI25 (OR, 4.74 [95% CI, 3.28-6.86]; I\u003csup\u003e2\u003c/sup\u003e = 35%; GRADE assessment: high certainty) when compared ruxolitinib to vehicle (\u003cstrong\u003eFigure 2\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eT-VASI90, T-VASI75, T-VASI50 and T-VASI25\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, involving a total of 830 patients, were included in the meta-analysis to assess the effectiveness of ruxolitinib compared to vehicle by T-VASI90, T-VASI75, T-VASI50 and T-VASI25. The meta-analysis results demonstrated that the use of ruxolitinib did not significantly increase the likelihood of participants achieving T-VASI90 compared to vehicle (OR, 1.47 [95% CI, 0.24-9.09]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: moderate certainty). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving T-VASI75 (OR, 2.78 [95% CI, 1.10-7.00]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: moderate certainty), T-VASI50 (OR, 4.47 [95% CI, 2.52-7.92]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: high certainty), and T-VASI25 (OR, 3.45 [95% CI, 2.40-4.96]; I\u003csup\u003e2\u003c/sup\u003e = 3%; GRADE assessment: high certainty) when compared ruxolitinib to vehicle (\u003cstrong\u003eFigure 2\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eVNS-4 or 5\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe meta-analysis of two trials, involving a total of 673 patients, demonstrated that the use of ruxolitinib led to a higher proportion of participants achieving VNS-4 or 5 (OR, 6.15 [95% CI, 3.14-12.05]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: moderate certainty) in comparison to vehicle (\u003cstrong\u003eFigure 2\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eF-VASI and T-VASI\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, which included 830 patients, reported the outcome of percentage change from baseline of F-VASI scores. The results showed that ruxolitinib were associated with more lowered percentage change of F-VASI scores from baseline (MD, \u0026ndash;32.79 [95% CI, \u0026minus;36.37 to \u0026minus;29.21]; I\u003csup\u003e2\u003c/sup\u003e = 97%; GRADE assessment: moderate certainty) compared to vehicle. Three trials, which included 830 patients, reported the outcome of percentage change from baseline of T-VASI scores. The results showed that ruxolitinib were associated with more lowered percentage change of T-VASI scores from baseline (MD, \u0026ndash;20.22 [95% CI, \u0026minus;23.11 to \u0026minus;17.33]; I\u003csup\u003e2\u003c/sup\u003e = 98%; GRADE assessment: moderate certainty) compared to vehicle (\u003cstrong\u003eFigure 3\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eF-BSA and T-BSA\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo trials, which included 673 patients, reported the outcome of percentage change from baseline of F-BSA scores. The results showed that ruxolitinib were associated with more lowered percentage change of F-BSA scores from baseline (MD, \u0026ndash;19.40 [95% CI, \u0026minus;19.91 to \u0026minus;18.89]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: high certainty) compared to vehicle. Two trials, which included 673 patients, reported the outcome of percentage change from baseline of T-BSA scores. The results showed that ruxolitinib were associated with more lowered percentage change of T-BSA scores from baseline (MD, \u0026ndash;10.50 [95% CI, \u0026minus;13.34 to \u0026minus;7.67]; I\u003csup\u003e2\u003c/sup\u003e = 99%; GRADE assessment: high certainty) compared to vehicle (\u003cstrong\u003eFigure 3\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Findings on quality of life\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo trials, which included 673 patients, reported the outcome of change from baseline of DLQI scores. The results showed that ruxolitinib were associated with more lowered change of DLQI scores from baseline (MD, \u0026ndash;0.46 [95% CI, \u0026minus;0.73 to \u0026minus;0.19]; I\u003csup\u003e2\u003c/sup\u003e = 95%; GRADE assessment: moderate certainty) compared to vehicle (\u003cstrong\u003eSupplement figure 1\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.6 Findings on safety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, which included 830 patients, reported these outcomes of TEAEs, SAEs and discontinuation due to AEs. The meta-analysis results indicated that there may not be a significant difference in the occurrence of TEAEs (RR, 1.46 [95% CI, 0.85-2.49]; I\u003csup\u003e2\u003c/sup\u003e = 53%; GRADE assessment: high certainty), SAEs (RR, 2.25 [95% CI, 0.59-8.67]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: moderate certainty), and discontinuation due to AEs (RR, 0.38 [95% CI, 0.10-1.48]; I\u003csup\u003e2\u003c/sup\u003e = 0%; GRADE assessment: high certainty) between ruxolitinib and vehicle (\u003cstrong\u003esupplement figure 5\u003c/strong\u003e; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.7 Another analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubgroup analyses and assessments of publication bias were not conducted due to the limited number of clinical trials included in the analysis (only three trials) and the fact that all trials were conducted by the same research group, performing subgroup analyses and assessing publication bias may not be appropriate or informative.\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn patients with vitiligo, we found moderate-certainly or high-certainly evidence that ruxolitinib cream improves clinical symptoms compared to vehicle cream, particularly in reducing facial vitiligo. Although there is moderate-quality evidence that ruxolitinib cream improves quality of life in vitiligo patients compared to vehicle cream, the observed mean decrease of 0.46 scores was not practically significant in relation to a total score of 30. Current evidence supports the safety of ruxolitinib as a topical treatment for vitiligo.\u003c/p\u003e \u003cp\u003eThis systematic review and meta-analysis have several notable strengths. These include a comprehensive search strategy to identify eligible trials, independent assessment of study selection, data extraction, and risk of bias by two reviewers, and the application of the GRADE approach to evaluate the certainty of evidence. Furthermore, the presentation of absolute effect measures enhances the interpretability of the findings, facilitating a more meaningful understanding of the clinical implications.\u003c/p\u003e \u003cp\u003eLimitations of this systematic review and meta-analysis are as follows: 1) All three trials were conducted by the same research group introduces potential bias and may impact the reliability of the results, but this also reduces inherent heterogeneity among the trials; 2) Despite the inclusion of large sample sizes, the limited number of trials results in wider CIs for certain outcomes, which lowers the level of certainty in the evidence; 3) All participants were from Europe and America, so it remains to be determined whether the findings of our study are applicable to patients of Asian and African; 4) Due to the limited number of trials, subgroup analyses predefined by clinical experts, different doses of ruxolitinib, could not be done; 5) The fingdings of our study are based on short-term treatment (24 weeks) with ruxolitinib, and the long-term efficacy and safety of ruxolitinib are currently unknown. Future trials should ideally address these issues, and it is necessary to update this study timely.\u003c/p\u003e \u003cp\u003eVitiligo is categorized into three distinct forms based on the distribution of skin lesions: non-segmental, segmental, and mixed vitiligo \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Non-segmental vitiligo is the most common form. The symmetrical nature of the white patches is a distinguishing feature of non-segmental vitiligo, differentiating it from other forms of the condition \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Non-segmental vitiligo and segmental vitiligo are believed to have distinct pathogenetic mechanisms due to their differing clinical patterns. However, recent data suggest that there may be overlapping inflammatory mechanisms involved in both segmental and non-segmental vitiligo that contributing to the development of both subtypes \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In our study, the majority (98.7%) of the vitiligo cases included were non-segmental vitiligo. Therefore, clinicians should carefully consider the evidence provided by this study when making treatment decisions for different subtypes of vitiligo. Future trials should be conducted to specifically investigate the efficacy of ruxolitinib in each subtype of vitiligo that can gain a clearer understanding of the treatment's efficacy and applicability in diverse patient populations.\u003c/p\u003e \u003cp\u003eCurrently, there are many treatment options for vitiligo, and in many clinical situations, combination therapy needs to be considered \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The majority of participants included in our study had a history of prior therapy, including topical corticosteroids, calcineurin inhibitors, phototherapy and photochemotherapy, indicating that they were not first-episode patients. Indeed, the effectiveness of ruxolitinib specifically for first-episode vitiligo patients and the potential benefits of combining it with other treatments require further investigation \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Conducting future trials based on these hypotheses would provide valuable insights into the comparative efficacy of ruxolitinib in different patient populations and the potential synergistic effects of combination therapies that will contribute to advancing our understanding of the optimal treatment strategies for vitiligo.\u003c/p\u003e \u003cp\u003eThe skin plays a central role in various aspects of life. Many patients with vitiligo experience elevated levels of stress and often face social stigma due to their visible skin depigmentation \u003csup\u003e[\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. In addition to the effectiveness of the treatment, various factors can contribute to the overall quality of life of patients with vitiligo, such as age at onset, extent, distribution, stigma, self-esteem and self-concept. Therefore, the lack of practically significant improvement observed in our study does not show that ruxolitinib is incapable of improving the quality of life in individuals with vitiligo. Indeed, the duration of treatment and the follow-up period can also significantly impact the assessment of quality of life outcomes in patients with vitiligo. The short-term nature of the treatment duration in the current study (24 weeks) may not have been sufficient to capture the full potential of ruxolitinib in improving quality of life. Additionally, long-term follow-up is necessary to evaluate the sustained effects of the treatment on patients' well-being over time. It is plausible that extended treatment duration and longer follow-up periods could yield different results and potentially demonstrate a positive impact of ruxolitinib on the quality of life of individuals with vitiligo. Similarly, the safety assessment of ruxolitinib in the treatment of vitiligo would benefit from studies with longer follow-up periods and larger sample sizes.\u003c/p\u003e \u003cp\u003eTo our knowledge, this systematic review and meta-analysis is the first to evaluate the efficacy and safety of ruxolitinib for patients with vitiligo. Unlike previous reviews \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, our study has several distinct features. Firstly, it exclusively incorporates evidence from randomized controlled trials. Secondly, we employed the GRADE approach to evaluate the certainty of the evidence, providing a comprehensive and standardized assessment of the quality of the included studies. Lastly, to facilitate interpretation, we presented the absolute effects of ruxolitinib treatment.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eThe results of our study provide compelling evidence for the efficacy of ruxolitinib in the short-term treatment of vitiligo. These findings indicate that ruxolitinib cream has the potential to be a promising treatment option for vitiligo. However, it is important to note that further study is necessary to evaluate the sustained efficacy and safety of ruxolitinib over a longer duration. Long-term and larger sample sizes studies are crucial in determining the prolonged effects and safety profile of ruxolitinib in the treatment of vitiligo.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYY, HD and YTZ planned and designed the study. YY and LZ developed search strategies. YY, LZ, SHY, and XTG screened potential studies and extracted data from the included studies. YY and LZ managed the data and performed the statistical analysis. HD conducted the arbitration under disagreement and ensured that there were no errors. HD and YTZ provided methodological support and helped to interpret findings. YY wrote the first draft. HD and YTZ revised the draft. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eEzzedine K, Eleftheriadou V, Whitton M, et al. Vitiligo. Lancet. 2015;386(9988):74-84.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBergqvist C, Ezzedine K. Vitiligo: A Review. Dermatology. 2020;236(6):571-592.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKr\u0026uuml;ger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206-1212.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAlikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-491.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZhang Y, Cai Y, Shi M, et al. The Prevalence of Vitiligo: A Meta-Analysis. PLoS One. 2016;11(9): e0163806.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSehgal VN, Srivastava G. Vitiligo: compendium of clinico-epidemiological features. Indian J Dermatol Venereol Leprol. 2007;73(3):149-156.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eElbuluk N, Ezzedine K. Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients. Dermatol Clin. 2017;35(2):117-128. Bibeau K, Pandya AG, Ezzedine K, et al. Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA. J Eur Acad Dermatol Venereol. 2022;36(10):1831-1844.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOngenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res. 2003;16(2):90-100.\u003c/li\u003e\n \u003cli\u003eQi F, Liu F, Gao L. Janus Kinase Inhibitors in the Treatment of Vitiligo: A Review. Front Immunol. 2021; 12:790125.\u003c/li\u003e\n \u003cli\u003eRosmarin D, Passeron T, Pandya AG, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022;387(16):1445-1455.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020;396(10244):110-120.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRosmarin D, Passeron T, Pandya AG, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022;387(16):1445-1455.\u003c/li\u003e\n \u003cli\u003eGao Y, Yang K, Cai Y, et al. Updating systematic reviews can improve the precision of outcomes: a\u0026nbsp;comparative study. J Clin Epidemiol. 2020; 125:108-119.\u003c/li\u003e\n \u003cli\u003eHiggins JPT, Thomas J, Chandler J,\u0026nbsp;et al.\u0026nbsp;\u003cem\u003eCochrane Handbook for Systematic Reviews of Interventions\u003c/em\u003e version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.\u003c/li\u003e\n \u003cli\u003ePage MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Busse JW. Modification of Cochrane tool to assess risk of bias in randomized trials. https://www.evidencepartners.com/resources/methodological-resources/.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650): 924-926.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Vist G, et al. GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). J Clin Epidemiol. 2011;64(4): 407-415.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol. 2011;64(12): 1283-1293.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 7. Rating the quality of evidence--inconsistency. J Clin Epidemiol. 2011;64(12): 1294-1302.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 8. Rating the quality of evidence--indirectness. J Clin Epidemiol. 2011;64(12): 1303-1310.\u003c/li\u003e\n \u003cli\u003eGuyatt GH, Oxman AD, Montori V, et al. GRADE guidelines: 5. Rating the quality of evidence--publication bias. J Clin Epidemiol. 2011;64(12): 1277-1282.\u003c/li\u003e\n \u003cli\u003ePicardo M, Dell\u0026apos;Anna ML, Ezzedine K, et al. Vitiligo. Nat Rev Dis Primers. 2015;1: 15011.\u003c/li\u003e\n \u003cli\u003eShin S, Shin JY, Lee H, et al. Spreading of pre-existing segmental vitiligo after immunotherapy with house dust mite in a patient with atopic dermatitis. Clin Exp Dermatol. 2015;40(8): 920-921.\u003c/li\u003e\n \u003cli\u003eEleftheriadou V, Atkar R, Batchelor J, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021. Br J Dermatol. 2022;186(1): 18-29.\u003c/li\u003e\n \u003cli\u003eSpeeckaert R, van Geel N. Vitiligo: An Update on Pathophysiology and Treatment Options. Am J Clin Dermatol. 2017;18(6): 733-744.\u003c/li\u003e\n \u003cli\u003eCunningham KN, Rosmarin D. Vitiligo Treatments: Review of Current Therapeutic Modalities and JAK Inhibitors. Am J Clin Dermatol. 2023;24(2): 165-186.\u003c/li\u003e\n \u003cli\u003eSilverberg JI, Silverberg NB. Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 2013;149(2): 159-164.\u003c/li\u003e\n \u003cli\u003eWong SM, Baba R. Quality of life among Malaysian patients with vitiligo. Int J Dermatol. 2012;51(2): 158-161.\u003c/li\u003e\n \u003cli\u003eMorrison B, Burden-Teh E, Batchelor JM, et al. Quality of life in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2017;177(6): e338-e339.\u003c/li\u003e\n \u003cli\u003eHwang JR, Driscoll MS. Review of Ruxolitinib for Treatment of Non-Segmental Vitiligo. Ann Pharmacother. 2022: 10600280221143748.\u003c/li\u003e\n \u003cli\u003eTavoletti G, Avallone G, Conforti C, et al. Topical ruxolitinib: A new treatment for vitiligo. J Eur Acad Dermatol Venereol. 2023; 0: 1-9.\u003c/li\u003e\n \u003cli\u003eSmith P, Yao W, Shepard S, et al. Developing a JAK Inhibitor for Targeted Local Delivery: Ruxolitinib Cream. Pharmaceutics. 2021;13(7): 1044.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e List of included trials and baseline characteristics\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1019\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.360157016683022%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample sizes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.986261040235525%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProportion of males, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.77134445534838%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProportion of females, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, mean (SD), y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.21099116781158%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention (sample sizes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (sample sizes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.71540726202159%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of vitiligo, mean (SD), y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.243375858684985%\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of vitiligo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF-VASI scores, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF-BSA scores, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.360157016683022%\" rowspan=\"4\"\u003e\n \u003cp\u003eRosmarin 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\" rowspan=\"4\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\" rowspan=\"4\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.986261040235525%\" rowspan=\"4\"\u003e\n \u003cp\u003e73, 46.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.77134445534838%\" rowspan=\"4\"\u003e\n \u003cp\u003e84, 53.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\" rowspan=\"4\"\u003e\n \u003cp\u003e48.3 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.21099116781158%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (0.15%), qd, 24 weeks (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\" rowspan=\"4\"\u003e\n \u003cp\u003eVehicle cream (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.71540726202159%\" rowspan=\"4\"\u003e\n \u003cp\u003e9.7 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.243375858684985%\" rowspan=\"4\"\u003e\n \u003cp\u003eSegmental (11), non-Segmental (146)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\" rowspan=\"4\"\u003e\n \u003cp\u003e1.3 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\" rowspan=\"4\"\u003e\n \u003cp\u003e1.5 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\" rowspan=\"4\"\u003e\n \u003cp\u003eIncyte\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (0.50%), qd, 24 weeks (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (1.50%), qd, 24 weeks (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (1.50%), bid, 24 weeks (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.360157016683022%\"\u003e\n \u003cp\u003eRosmarin 2022\u003cbr\u003e\u0026nbsp;(TRuE-V1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003eUSA, Canada, Bulgaria, France, Germany, Italy, the Netherlands, Poland, Spain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.986261040235525%\"\u003e\n \u003cp\u003e144, 43.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.77134445534838%\"\u003e\n \u003cp\u003e186, 56.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003e40.2 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.21099116781158%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (1.50%), qd, 24 weeks (221)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003eVehicle cream (109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.71540726202159%\"\u003e\n \u003cp\u003e13.6 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.243375858684985%\"\u003e\n \u003cp\u003eSegmental (0), non-Segmental (330)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e1.0 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003e1.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003eIncyte\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.360157016683022%\"\u003e\n \u003cp\u003eRosmarin 2022\u003cbr\u003e\u0026nbsp;(TRuE-V2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003eUSA, Canada, Bulgaria, France, Germany, Italy, the Netherlands, Poland, Spain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.986261040235525%\"\u003e\n \u003cp\u003e171, 49.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.77134445534838%\"\u003e\n \u003cp\u003e172, 50.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003e38.9 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.21099116781158%\"\u003e\n \u003cp\u003eTopical Ruxolitinib cream (1.50%), qd, 24 weeks (228)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.182531894013739%\"\u003e\n \u003cp\u003eVehicle cream (115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.71540726202159%\"\u003e\n \u003cp\u003e15.9 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.243375858684985%\"\u003e\n \u003cp\u003eSegmental (0), non-Segmental (343)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003e0.9 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.458292443572129%\"\u003e\n \u003cp\u003e1.0 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.4769381746810595%\"\u003e\n \u003cp\u003eIncyte\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e GRADE summary of findings for ruxolitinib versus vehicle cream treatment for vitiligo\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"705\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eTimeframe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy results and measurements\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.24822695035461%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsolute effect estimates\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCertainty of the Evidence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(Quality of evidence)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlain language summary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eVehicle cream\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eRuxolitinib Cream\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving F-VASI90\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 9.61\u003c/p\u003e\n \u003cp\u003e(CI 95% 3.67 - 25.19)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e105\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious imprecision\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably improves percentage of participants achieving F-VASI90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e93 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 31 more - 222 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving F-VASI75\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 4.34\u003c/p\u003e\n \u003cp\u003e(CI 95% 2.67 - 7.06)\u003c/p\u003e\n \u003cp\u003eBased on data from 30 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e78\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e269\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream improves percentage of participants achieving F-VASI75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e191 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 106 more - 296 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving F-VASI50\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 4.71\u003c/p\u003e\n \u003cp\u003e(CI 95% 3.24 - 6.81)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e164\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e480\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream improves percentage of participants achieving F-VASI50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e316 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 225 more - 408 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving F-VASI25\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 4.74\u003c/p\u003e\n \u003cp\u003e(CI 95% 3.28 - 6.86)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e273\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e640\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream improves percentage of participants achieving F-VASI25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e367 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 279 more - 447 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving T-VASI90\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 1.47\u003c/p\u003e\n \u003cp\u003e(CI 95% 0.24 - 9.09)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious imprecision\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably improves percentage of participants achieving T-VASI90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e3 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 5 fewer - 46 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving T-VASI75\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 2.78\u003c/p\u003e\n \u003cp\u003e(CI 95% 1.1 - 7.0)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e43\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious imprecision\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably improves percentage of participants achieving T-VASI75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e27 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 2 more - 86 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving T-VASI50\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 4.47\u003c/p\u003e\n \u003cp\u003e(CI 95% 2.52 - 7.92)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e51\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e194\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream improves percentage of participants achieving T-VASI50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e143 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 68 more - 248 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving T-VASI25\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 3.45\u003c/p\u003e\n \u003cp\u003e(CI 95% 2.4 - 4.96)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e191\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e449\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream improves percentage of participants achieving T-VASI25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e258 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 171 more - 348 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage of participants achieving VNS4 or 5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eOdds ratio: 6.15\u003c/p\u003e\n \u003cp\u003e(CI 95% 3.14 - 12.05)\u003c/p\u003e\n \u003cp\u003eBased on data from 673 participants in 2 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e40\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e204\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious imprecision\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably improves percentage of participants achieving VNS4 or 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e164 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 76 more - 294 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003eTreatment-related adverse events\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eRelative risk: 1.46\u003c/p\u003e\n \u003cp\u003e(CI 95% 0.85 - 2.49)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e109\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e159\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream has little or no difference on treatment-related adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e50 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 16 fewer - 162 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003eSerious adverse events\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eRelative risk: 2.25\u003c/p\u003e\n \u003cp\u003e(CI 95% 0.59 - 8.67)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious imprecision\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably has little or no difference on serious adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e5 more per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 2 fewer - 31 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003eAdverse events leading to discontinuation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eRelative risk: 0.38\u003c/p\u003e\n \u003cp\u003e(CI 95% 0.1 - 1.48)\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eper 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream has more or no difference on adverse events leading to discontinuation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003e7 fewer per 1000\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 11 fewer - 6 more)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage change from baseline F-VASI scores\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eMeasured by:\u003c/p\u003e\n \u003cp\u003eScale: \u0026nbsp;- \u0026nbsp; \u0026nbsp; Lower better\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-15.8\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-48.59\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious inconsistency\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably decreases percentage change from baseline F-VASI scores\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003eMD 32.79 lower\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 36.37 lower - 29.21 lower)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage change from baseline T-VASI scores\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eMeasured by:\u003c/p\u003e\n \u003cp\u003eScale: \u0026nbsp;- \u0026nbsp; \u0026nbsp; Lower better\u003c/p\u003e\n \u003cp\u003eBased on data from 830 participants in 3 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-8.99\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-29.21\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious inconsistency\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably decreases percentage change from baseline T-VASI scores\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003eMD 20.22 lower\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 23.11 lower - 17.33 lower)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage change from baseline F-BSA scores\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eMeasured by:\u003c/p\u003e\n \u003cp\u003eScale: \u0026nbsp;- \u0026nbsp; \u0026nbsp; Lower better\u003c/p\u003e\n \u003cp\u003eBased on data from 673 participants in 2 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-8.25\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-27.65\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream decreases percentage change from baseline F-BSA scores\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003eMD 19.4 lower\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 19.91 lower - 18.89 lower)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003ePercentage change from baseline T-BSA scores\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eMeasured by:\u003c/p\u003e\n \u003cp\u003eScale: \u0026nbsp;- \u0026nbsp; \u0026nbsp; Lower better\u003c/p\u003e\n \u003cp\u003eBased on data from 673 participants in 2 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-3.15\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-13.65\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream decreases percentage change from baseline T-BSA scores\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003eMD 10.5 lower\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 13.34 lower - 7.67 lower)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.46808510638298%\" rowspan=\"2\"\u003e\n \u003cp\u003eChange from baseline DLQI scores\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.72340425531915%\" rowspan=\"2\"\u003e\n \u003cp\u003eMeasured by:\u003c/p\u003e\n \u003cp\u003eScale: \u0026nbsp;- \u0026nbsp; \u0026nbsp; Lower better\u003c/p\u003e\n \u003cp\u003eBased on data from 673 participants in 2 studies\u003c/p\u003e\n \u003cp\u003eFollow up 24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.72\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.624113475177305%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-1.18\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.113475177304963%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDue to serious inconsistency\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.4468085106383%\" rowspan=\"2\"\u003e\n \u003cp\u003eRuxolitinib cream probably decreases change from baseline DLQI scores slightly\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eDifference: \u003cstrong\u003eMD 0.46 lower\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(CI 95% 0.73 lower - 0.19 lower)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e1. Rated down 1 level for serious imprecision due to wide confidence intervals; 2. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=97%); 3. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=98%); 4. Rated down 1 level for serious inconsistency: serious due to statistical (I^2=95%).\u003c/p\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":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ruxolitinib, Efficacy, Safety, Systematic review, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-3171294/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3171294/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eImportance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVitiligo is a chronic skin disorder causing depigmentation. There is lack of evidence-based medical evidence regarding ruxolitinib efficacy and safety for Vitiligo.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the efficacy and safety of ruxolitinib cream in treatment vitiligo.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe databases of PubMed, Embase, and Cochrane Library were searched. The literature screening was independently conducted by two reviewers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction and synthesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor continuous variables, weighted mean difference (WMD) along with a 95% confidence interval (CI) was performed. For dichotomous outcomes, we calculated the odds ratios (ORs) or risk ratios (RRs), and their corresponding 95% CIs. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMain outcomes and measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSymptoms, quality of life, and safety were evaluated using various measures, including the Facial Vitiligo Area Scoring Index (F-VASI), Total Vitiligo Area Scoring Index (T-VASI), Facial Body Surface Area (F-BAS), Total Body Surface Area (T-BAS) and Treatment-emergent Adverse Events (TEAEs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree trials, involving a total of 830 participants from nine countries were included (female: 388, 46.7%, male: 442, 53.3%). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI75 (OR, 4.34 [95% CI, 2.67-7.06]; high), F-VASI50 (OR, 4.71 [95% CI, 3.24-6.84]; high), T-VASI75 (OR, 2.78 [95% CI, 1.10-7.00]; moderate), and T-VASI50 (OR, 4.47 [95% CI, 2.52-7.92]; high) when compared ruxolitinib to vehicle. Ruxolitinib were associated with more lowered percentage change of F-VASI scores (MD, –32.79 [95% CI, −36.37 to −29.21]; moderate), and T-VASI scores (MD, –20.22 [95% CI, −23.11 to −17.33]; moderate) from baseline compared to vehicle. There may not be a significant difference in the occurrence of TEAEs between ruxolitinib and vehicle (RR, 1.46 [95% CI, 0.85-2.49]; high).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings suggest that ruxolitinib cream holds promise as a treatment option for vitiligo. Further long-term studies are needed to assess its sustained efficacy and safety profile.\u003c/p\u003e","manuscriptTitle":"Short-Term (24 Weeks) Treatment Efficacy and Safety of Ruxolitinib Cream in Participants with Vitiligo: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-19 15:05:48","doi":"10.21203/rs.3.rs-3171294/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2024-07-16T04:53:35+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-07-02T21:02:23+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-17T11:34:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-07-24T02:39:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2023-07-14T13:34:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b41ead07-323e-4469-92c2-f8df4fb60aaf","owner":[],"postedDate":"March 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-07T16:03:50+00:00","versionOfRecord":{"articleIdentity":"rs-3171294","link":"https://doi.org/10.1186/s13643-024-02653-7","journal":{"identity":"systematic-reviews","isVorOnly":false,"title":"Systematic Reviews"},"publishedOn":"2024-10-02 15:57:57","publishedOnDateReadable":"October 2nd, 2024"},"versionCreatedAt":"2024-03-19 15:05:48","video":"","vorDoi":"10.1186/s13643-024-02653-7","vorDoiUrl":"https://doi.org/10.1186/s13643-024-02653-7","workflowStages":[]},"version":"v1","identity":"rs-3171294","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3171294","identity":"rs-3171294","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}