Dataset Information

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

ABSTRACT:

Background

Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA.

Methods

Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal.

Results

Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo.

Conclusion

Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.

SUBMITTER: He Y

PROVIDER: S-EPMC3819708 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

He Ying Y Wong Angel Y S AY Chan Esther W EW Lau Wallis C Y WC Man Kenneth K C KK Chui Celine S L CS Worsley Alan J AJ Wong Ian C K IC

BMC musculoskeletal disorders 20131018

<h4>Background</h4>Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA.<h4>Methods</h4>Electronic and clinical ...[more]

PMID: 24139404

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Project description:IntroductionPeficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment.MethodsWe searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity.ResultsThe network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes.ConclusionsPeficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors.

Project description:The aim of the present study was to conduct a meta-analysis of the effectiveness of tofacitinib, a novel oral Janus kinase inhibitor, recently approved for the treatment of active rheumatoid arthritis in patients who have failed previous treatment with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, and other databases till 3 May 2013. All included studies were analyzed with the use of the Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Nine randomized controlled trials (RCTs) comparing tofacitinib with placebo were identified. Two of them additionally provided the comparison with adalimumab. However, only eight RCTs met the inclusion criteria for the meta-analysis. The overall results of the meta-analysis showed that tofacitinib provided a statistically significant improvement according to the response criteria (ACR20/50/70) after 12 weeks of treatment when compared to placebo (p < 0.00001). Moreover, it was demonstrated that tofacitinib was significantly superior to adalimumab in achieving the ACR50 response criteria at week 12 (p = 0.003). For the safety analysis, there were no statistically significant differences between tofacitinib-, adalimumab-, and placebo-treated patients in respect to the risk of serious adverse events or treatment discontinuation due to adverse reactions (p > 0.05). The findings of this systematic review with meta-analysis indicate that tofacitinib monotherapy or with background methotrexate provides early statistically significant and clinically important improvement in rheumatoid arthritis symptoms and has an acceptable safety profile comparable to that of placebo. The results of the present meta-analysis show that the frequency of serious adverse events was not increased after tofacitinib treatment. In addition, tofacitinib might provide an effective treatment option compared to intravenous or subcutaneous biological DMARDs, as suggested by the result of the comparison made regarding tofacitinib vs. adalimumab ACR50 response rate.

Project description:BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.MethodsORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ?1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.ResultsORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.ConclusionsTofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.Clinical trial identifierNCT00856544 and NCT00413699.

Project description:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib).A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods.The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively.In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

Project description:BACKGROUND:Rheumatoid arthritis has the characteristics of slow progression, long course, and repeated attacks. At present, western medicine commonly used in clinical practice not only reduces pain and improves symptoms, but also has more adverse reactions, affecting the health, and life of patients. In ancient China, Huangqi Guizhi Wuwu decoction was used by doctors to treat rheumatoid arthritis, with remarkable effect. In recent years, many clinical studies have also shown that Huangqi Guizhi Wuwu decoction has reliable effect in treating rheumatoid arthritis, but there is no evidence of evidence-based medicine. Therefore, this study aims to systematically evaluate the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. METHODS:Using computer to retrieve PubMed, The Cochrance Library, Embase, Web of Science, CNKI, VIP and Wanfang database, in addition manually retrieve Google academic and Baidu academic to collect all randomized controlled trials for Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis, including relevant academic journal and conference papers, dissertations, from the establishment of the database to July 2020. After 2 evaluators independently screened the literature, extracted the data, and evaluated the risk of bias included in the study, RevMan5.3 software was used to analyze the data. RESULTS:This research evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction in treating Rheumatoid arthritis from the aspects of clinical efficacy rate, visual analog scale (VAS), swollen joint count (SJC), morning stiffness time, Rrythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and adverse reaction incidence. CONCLUSION:This study will provide reliable evidence for the clinical application of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. ETHICS AND DISSEMINATION:The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/RZY3V.

Project description:Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new Syk inhibitor, are either invalid or insufficient. Through a systematic review and meta-analysis, we evaluated the efficacy and safety of fostamatinib at different dosages in rheumatoid arthritis patients that display an inadequate response to methotrexate or disease-modifying antirheumatic drugs. Methods: Randomized controlled trials published between January 2000 and November 2018 were retrieved from PubMed, Embase, Medline, Web of Science, and The Cochrane Library. We also searched a relevant website (www.clinicaltrials.gov) for retrieval of unpublished data. These studies compared different dosages of fostamatinib to placebo, including the intake of 100 mg fostamatinib twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) vs. the intake of 100 mg bid. Results: Two investigators analyzed 11 randomized placebo-controlled trials consisting of 3,680 patients. Compared to placebo, fostamatinib resulted in an obvious reduction in the American College of Rheumatology 20% response standard [weighted mean difference (WMD) 1.96, 95% confidence interval (CI) [1.46, 2.61], P < 0.001] and disease activity score < 2.6 (WMD 4.70, 95% CI [3.14, 7.03], P < 0.001). Regarding safety, the incidence of serious adverse reactions was higher in the fostamatinib group than in the placebo group [risk ratio (RR) 2.10, 95% CI [1.57, 2.80], P < 0.001]. The same was true for other adverse events [RR 1.63, 95%CI [1.33, 2.01], P < 0.001]. Conclusions: Fostamatinib is an effective and safe therapeutic medicine administered to patients with rheumatoid arthritis over 24 weeks. It can alleviate the degree of swelling and inflammation of the joints. Furthermore, 100 mg bid can be considered the most beneficial regimen over a 24-week period. More data are however needed to clarify the incidence of other adverse events and serious adverse reactions.

Dataset Information

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

Similar Datasets

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