scholarly journals A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

2020 ◽  
Vol 7 (1) ◽  
pp. 10-23
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Janus Kinase ◽  
Sensitivity Analyses ◽  
Baseline Risk ◽  
Inadequate Response ◽  
Primary Analysis ◽  
American College Of Rheumatology ◽  
Meta Analyses

Background/Objectives: This article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response. Results: Nineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999–2017), during which patient characteristics and treatment approaches might have changed. Conclusion: This NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results.

scholarly journals POS0665 TRAJECTORIES OF GLUCOCORTICOID-THERAPY IN EARLY RHEUMATOID ARTHRITIS: FIRST RESULTS OF A SCOPING SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL COHORT STUDIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 575.1-575
Author(s):  
A. Palmowski ◽  
F. Buttgereit
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Search Strategy ◽  
Meta Analysis ◽  
Term Treatment ◽  
Sensitivity Analyses ◽  
Published Data ◽  
Glucocorticoid Treatment ◽  
Long Term Treatment ◽  
Meta Analyses

Background:Glucocorticoids (GCs) are regularly used as a bridging therapy in early rheumatoid arthritis (eRA). As long-term treatment, especially at higher dosages, may lead to undesirable adverse events, GCs should be tapered as rapidly as clinically feasible.Objectives:To assess real-world trajectories of GC-therapy initiated in patients with eRA and in methotrexate-naïve RA patients.Methods:We conducted a scoping search in MEDLINE (via PubMed) to find articles (years 2005 – 2020) reporting on eRA (or methotrexate-naïve RA) patients from observational cohorts who start or take GCs at baseline. Articles had to describe either dosages or proportions of patients who took GCs or were able to taper GCs at two (minimum) pre-specified time points. The articles were screened by one reviewer (AP). Random-effects meta-analyses pooled results per outcome and time point if ≥3 studies were available. R software with package metafor was used for statistical analyses. A research protocol was published with protocols.io (10.17504/protocols.io.bpyfmptn).Results:Our highly specific search strategy yielded 165 results. Twelve articles on nine cohorts were finally included. Eight cohorts originated in Europe, one in Africa. At baseline, about half of the patients with eRA were prescribed GCs with a mean dosage of 8mg/d prednisone equivalent (fig 1). Over time, both the proportion taking GCs and the mean dosage declined. There was substantial heterogeneity between studies.Conclusion:Our results indicate that GCs remain regularly used drugs in eRA patients and in methotrexate-naïve patients with RA. While about 40% of patients still receive GCs after 24 months, mean dosages were tapered to “low” dosages (≤7.5mg/d prednisone equivalent)1 in all cohorts that reported respective data. Heterogeneity might be caused by country-specific differences. Unfortunately, the validity of sensitivity analyses would be poor due to the paucity of published data regarding GC dosages and proportions of patients taking GCs in observational RA cohorts. Major limitations of this scoping review are the very specific (and consequently less sensitive) search strategy and that the screening was conducted by one reviewer only.References:[1]Buttgereit F, Da Silva JAP, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61(8):718-22. doi: 10.1136/ard.61.8.718.Figure 1.Meta-analyses of proportions taking glucocorticoids and mean dosages at baseline and 24 months. GCs: Glucocorticoids; CI: Confidence interval.Disclosure of Interests:None declared

scholarly journals Meta-Analysis of Proptosis Response in Thyroid Eye Disease: Efficacy of EUGOGO Recommended Treatment Regimen With IV Methylprednisolone

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A842-A842
Author(s):  
Raymond S Douglas ◽  
Ryan Batten ◽  
Rana A Qadeer ◽  
Chris Cameron
Keyword(s):  
Study Design ◽  
Observational Studies ◽  
Meta Analysis ◽  
Thyroid Eye Disease ◽  
Recommended Dose ◽  
Sensitivity Analyses ◽  
Controlled Study ◽  
Eye Disease ◽  
Primary Analysis ◽  
Meta Analyses

Abstract Background: The European Group on Graves’ Orbitopathy (EUGOGO) recommends intravenous methylprednisolone (IVMP) as the first line treatment for moderate-to-severe active thyroid eye disease (TED). While many studies with varying doses of IVMP have reported improvements in inflammation, via clinical activity score (CAS) reduction, the reported improvements in the major progressive outcome of TED, proptosis, vary widely. A reduction in proptosis of ≥2 millimeter (mm) is considered by clinicians and EUGOGO as clinically meaningful. A meta-analysis of existing literature on use of IVMP in TED management, specifically proptosis response, was conducted. Methods: PubMed and Embase were searched for relevant randomized controlled trials (RCTs) and observational studies that included patients with moderate-to-severe active TED receiving treatment with the EUGOGO recommended dose of IVMP (4.5-5g over 12 weeks) from the inception of the databases to date of search (October 2020); regular alerts were established to capture any recent studies. The outcome of interest was change from baseline to week 12 in proptosis in mms. Single-arm meta-analyses were conducted for IVMP using the DerSimonian-Laird random-effects models and forest plots were generated. Pooled means and corresponding 95% confidence intervals (CIs) were calculated. The primary analysis included all identified studies. Sensitivity analyses were conducted based on study design, study characteristics (smoking status), and methodologies (weighted Bayesian meta-analyses based on study design). Results: The search retrieved 12 studies (10 single-center, 8 RCTs, 4 observational studies: 7 from China, 4 from EU, 1 from Turkey), reporting proptosis for 498 patients that were used for the meta-analysis. No placebo-controlled study with the EUGOGO recommended dose of IVMP was found. All studies included patients who were 18 years or older with moderate-to-severe TED and most (n=11) studies included patients with CAS of ≥3. For studies that reported this data, the mean or median (if mean not reported) age ranged from 35 to 52 years and duration of TED symptoms ranged from 4 to 13.6 months. Treatment with IVMP resulted in a reduction of 0.94 mm (95% CI: -1.57 to -0.32) in proptosis from baseline to week 12. The results from the sensitivity analyses were aligned with those from the primary analysis. Conclusions: Among patients with moderate-to-severe TED, this meta-analysis found the EUGOGO-recommended dose of IVMP may result in modest, but not clinically meaningful, improvements in proptosis. However, these results should be interpreted with caution given the paucity of published data and the lack of risk/benefit analyses with glucocorticoid use as compared to the recently FDA-approved therapy, teprotumumab, for the treatment of TED.

scholarly journals Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Evelien Bergrath ◽  
Robert A. Gerber ◽  
David Gruben ◽  
Tatjana Lukic ◽  
Charles Makin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Adverse Events ◽  
Systematic Literature Review ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Comparable Efficacy ◽  
Cochrane Central Register ◽  
Inadequate Response ◽  
Severe Rheumatoid Arthritis

Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs.

scholarly journals Efficacy and safety of filgotinib in combination with methotrexate in Japanese patients with active rheumatoid arthritis who have an inadequate response to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 1)

2021 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tsukasa Matsubara ◽  
Tatsuya Atsumi ◽  
Koichi Amano ◽  
Naoki Ishiguro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Once Daily ◽  
American College Of Rheumatology ◽  
Grade 3

ABSTRACT Objectives Evaluate the efficacy and safety of the Janus kinase-1 inhibitor filgotinib in Japanese patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX). Methods Data from 147 Japanese patients in FINCH 1, a 52-week global Phase 3 study, were analysed up to 24 weeks. Patients received once-daily filgotinib 200 or 100 mg, biweekly adalimumab, or placebo, all with stable background MTX. Results In the Japanese population, American College of Rheumatology 20% response rates at Week 12 (primary endpoint) were 77.5%, 65.9%, 53.6%, and 36.8% for filgotinib 200 mg, filgotinib 100 mg, adalimumab, and placebo. Proportions of patients achieving Disease Activity Score with 28 joints <2.6 at Week 24: filgotinib 200 mg, 65.0%; filgotinib 100 mg, 51.2%; adalimumab, 42.9%; and placebo, 5.3%. Incidence rates of serious infections: filgotinib 200 mg, 2.5%; filgotinib 100 mg, 0%; adalimumab, 10.7%; and placebo, 5.3%. Treatment-emergent laboratory abnormalities Grade ≥3 occurred in five (12.5%) filgotinib 200 mg, three (7.3%) filgotinib 100 mg, one (3.6%) adalimumab, and no placebo patients. No deaths were reported among Japanese patients. Conclusions Filgotinib once daily combined with MTX was effective and generally safe and well tolerated up to Week 24 in Japanese patients with RA and inadequate response to MTX.

scholarly journals Comparative Efficacy (DAS28 remission) of Targeted Immune Modulators for Rheumatoid Arthritis: A Network Meta-Analysis

2020 ◽  
Author(s):  
Jennie H. Best ◽  
Yuting Kuang ◽  
Yilin Jiang ◽  
Rajpal Singh ◽  
Andreas Karabis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Odds Ratio ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Phase Iii ◽  
Inadequate Response ◽  
Jak Inhibitors ◽  
Immune Modulators ◽  
Das28 Remission

Abstract Background The objective of the study was to evaluate the relative efficacy of targeted immune modulators (TIMs) in TIM-naïve/mixed (≤ 20% TIM-experienced) and TIM-experienced (> 20% TIM-experienced) adults with moderately-to-severe rheumatoid arthritis with an inadequate response or intolerance to conventional disease-modifying antirheumatic drugs (cDMARDs). Methods A fixed effects Bayesian network meta-analysis (NMA) was performed using published study-level data form 41 randomized controlled trials (RCTs), identified from 2 recent systematic literature reviews conducted by the Institute for Clinical and Economic Review, and 2 additional phase III trials for filgotinib (FINCH-1, FINCH-2). RCTs that compared TIMs to each other, cDMARD or placebo were included. Treatments included Janus kinase (JAK) inhibitors, tumor necrosis factor alpha inhibitors (TNFi), and other non-TNFis. Efficacy was defined as achieving remission with a DAS28 score < 2.6 at 12 and 24 weeks. Results In the 12-week analysis for the TIM-naïve/mixed population, all TIMs combined with cDMARD were more likely to achieve remission compared to cDMARD alone (statistically significant), with intravenous tocilizumab showing a substantially greater magnitude of effect (odds ratio = 19.36, 95% credible interval: 11.01, 38.16). Similarly, in the 24-week analysis, intravenous and subcutaneous tocilizumab showed the highest odds ratio of achieving DAS28 remission compared to cDMARD. Similar trends were observed for the analyses on monotherapy or TIM-experienced population. Conclusion This NMA demonstrated that tocilizumab is associated with a greater likelihood of remission (DAS28 < 2.6) at 12 and 24 weeks compared to most other TIMs including new JAK inhibitors, when used in combination with a cDMARD or as monotherapy, among TIM-naïve/mixed or TIM-experienced populations.

scholarly journals AB0237 INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH RITUXIMAB AND ANTI-TNF INHIBITOR

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1144.2-1144
Author(s):  
N. Zehraoui ◽  
R. Benaziez.Boutaleb ◽  
H. Hafirassou ◽  
F. Mechid ◽  
N. Bahaz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Best Practice ◽  
Biological Therapy ◽  
Patient Characteristics ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Clinical Rheumatology ◽  
Number Of Patients ◽  
Serious Infections ◽  
Comparative Risk

Background:Biological therapies have significantly improved the management of rheumatoid arthritis (RA). These molecules are very effective, but are known for their specific risks, especially infectious. It depends on several factors including the type of molecule used.Objectives:The objective of our study is to compare the rate of infection in RA patients treated with rituximab and anti-TNFα.Methods:Prospective, observational, monocentric study. Were included RA patients (ACR / EULAR 2010 criteria) treated with rituximab and anti-TNFα (adalimumab, infliximab and Etanercept) after inadequate response to DMARDs.Demographic characteristics, comorbidities, association with methotrexate and corticosteroids were collected and compared for each group.The number, type and severity of the infections in both cases were noted.SPSS (Statistical Package for Social Science) was used for data analysis.Results:40 RA patients treated with rituximab and 31 patients who received anti-TNFα were included.Patient characteristics and Comparison of rate of infection in RA patients between the two groups are summarized in Table 1Table 1.ParametersRituximabAnti-TNFαpNumber of patients4031Average age (years)56,2846,060,01Sexratio0,140,110,7Average duration of evolution (years)15,8313,740,3Patients under corticosteroid (%)97,587,10,08Average corticosteroid dose6,415,480,3patients under methotrexate (%)37,545,20,5Diabetes (%)2016,10,7Patients with infection (%)32,551,60,1Number of infections18240,4Number of serious infections500,04Conclusion:The rate of infections in patients with RA treated with rituximab or anti-TNF was similar. However, the infections observed were more serious in patients with RA treated with rituximabReferences:[1]Fabiola Atzeni MD PhD and al. Infections and Biological Therapy in Patients with Rheumatic Diseases. IMAJ . VOL 18. march-APRIL 2016.[2]Huifeng Yun and al. Comparative Risk of Hospitalized Infection Associated with Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. ARTHRITIS & RHEUMATOLOGY. Vol. 68, No. 1, January 2016, pp 56–66.[3]Manjari Lahiri and al. Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. Best Practice & Research Clinical Rheumatology (2015) 1-16.Disclosure of Interests:None declared

scholarly journals FRI0136 PERIPHERAL PROTEIN BIOMARKER CHANGES FOLLOWING SELECTIVE INHIBITION OF JANUS KINASE 1 (JAK1) BY FILGOTINIB IN ADULTS WITH MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH PRIOR INADEQUATE RESPONSE TO METHOTREXATE (FINCH1)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 650.2-651
Author(s):  
P. C. Taylor ◽  
E. Elboudwarej ◽  
B. Downie ◽  
J. Liu ◽  
R. E. Hawtin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Active Rheumatoid Arthritis ◽  
Immune Cell ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Bone Biology ◽  
Janus Kinase 1 ◽  
Immune Cell Migration ◽  
Dose Dependent

Background:Filgotinib (FIL), an oral selective Janus kinase 1 (JAK1) inhibitor has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA), including those with prior inadequate response to methotrexate (MTX) therapy (FINCH1;NCT02889796).Objectives:A longitudinal study of protein biomarkers related to JAK signaling1, bone biology2, immune cell migration2, and inflammation2was conducted to identify RA-associated markers altered by FIL vs MTX or adalimumab (ADA).Methods:FINCH1 RA patients (pts) were randomized to receive either a stable dose of MTX with placebo (PBO+MTX), ADA+MTX, and either FIL100mg+MTX or FIL200mg+MTX, once daily. Plasma, serum, and urine samples were taken from a subset of pts (~548) at baseline (BL) and weeks (wks) 4 and 12. Twenty-six pre-defined cytokines (biomarkers) were evaluated using ELISA. BL correlation between biomarkers and clinical response measures (DAS28CRP, SJC28, TJC28, CDAI, Patient Assessment and FACIT), were analyzed by Spearman Rank. Multiscale bootstrap resampling evaluated significant intra-cluster biomarker membership. Mean changes in biomarker levels from BL to wks 4 and 12 were compared between arms using PBO-adjusted estimates from a linear mixed effects model. A 5% false-discovery rate was applied for all analyses.Results:At BL, distinct biomarker-based pt clusters (CL) were identified. The strongest intra-group correlations were in bone-cartilage resorption/inflammation (CL1; Rho range 0.37–0.88) and JAK activity (CL2; Rho range 0.41–0.71). Individual BL cytokine levels were significantly associated with DAS28CRP, with unique biomarkers specific to various subcomponents of the score. Eleven biomarkers were associated with DAS28CRP, while 5, 3, and 2 were associated with CDAI, SJC28, and TJC28, respectively. The magnitude of FIL-associated treatment effects was time- and dose-dependent. Significant biomarker changes from BL were observed in FIL pts, relative to PBO+MTX pts. FIL100mg+MTX led to a significant change in 8 biomarkers by either 4 or 12 wks of treatment; FIL200mg+MTX significantly changed these and an additional 4 biomarkers by either time point. The greatest effect of FIL200mg+MTX was at 12 wks for CXCL13 (-38.4%) and IL6 (-53.7%). All treatment arms led to significant reductions in TNFα relative to PBO+MTX. FIL200mg+MTX treatment led to larger reductions of TNFα than ADA+MTX treatment at both wk4 (-24.7% vs -17.9%) and wk12 (-20.5% vs -12.2%), although the differences were not statistically significant.FIL and ADA caused differential patterns of cytokine response at either wks 4 or 12. Of 12 biomarkers with a significant FIL200mg+MTX treatment effect, there was a significantly larger reduction in TNFSF13B and CTX1 relative to ADA+MTX at 12 wks. Of 8 biomarkers with FIL100mg+MTX effects, only 2 (CXCL10 at wk 4; CXCL13 at wks 4 and 12) had significant differences from ADA+MTX. Relative either to FIL200mg+MTX or FIL100mg+MTX, and despite the same direction of effect, ADA+MTX led to a significantly larger reduction in CCL2, CXCL10, CCL4, and CXCL13.Conclusion:Compared with PBO, 12 wks of FIL treatment significantly reduced cytokines associated with JAK activity1, bone biology2, inflammation2, and immune cell migration2in MTX-IR pts. The effects were largely FIL dose-dependent; most cytokines exhibited similar effects regardless of treatment arms, but differential changes between FIL+MTX and ADA+MTX were observed, supportive of the different mechanisms of action of these therapies.References:[1]Majoros A, et al. Front Immunol. 2017;8:29[2]Brennan F, and McInnes I. J Clin Invest. 2008;118:3537-45Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc.

SAT0136 RELATIVE EFFICACY AND SAFETY OF TOFACITINIB, BARICITINIB, UPADACITINIB, AND FILGOTINIB, IN COMPARISON WITH ADALIMUMAB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.1-1005
Author(s):  
Y. H. Lee ◽  
G. G. Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Response Rate ◽  
Meta Analysis ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Randomized Controlled ◽  
Acr20 Response Rate

Background:Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is the most widely used DMARD for the treatment of rheumatoid arthritis (RA). However, not all patients are responsive to the drug; 30% of the patients discontinue therapy within 1 year of commencing the treatment, usually because of the lack of efficacy or undesirable adverse effects Small-molecule Janus kinase inhibitors are clinically developed for the treatment of RA.Objectives:The aim of this study is to investigate the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison with adalimumab in patients with active RA and having inadequate responses to MTX.Methods:We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients having inadequate responses to MTX.Results:Four RCTs, comprising 5,451 patients, met the inclusion criteria. The baricitinib 4mg+MTX and upadacitinib 15mg+MTX group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the adalimumab 40mg+MTX group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4mg+MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15mg+MTX, tofacitinib 5mg+MTX, filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, and placebo+MTX. The upadacitinib 15mg+MTX and baricitinib 4mg+MTX groups showed significantly higher ACR50 and ACR70 response rates than adalimumab 40mg+MTX. In terms of Herpes zoster infection, the ranking probability based on the SUCRA indicated that placebo+MTX were likely to be the safest treatments, followed by filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, tofacitinib 5mg+MTX, upadacitinib 15mg+MTX, and baricitinib 4mg+MTX. Regarding safety analysis, no statistically significant differences were found between the respective intervention groups.Conclusion:In RA patients with an inadequate response to MTX, baricitinib 4mg+MTX and upadacitinib 15mg+MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.References:[1]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, DeMasi R, Soma K, Zhang R, Takiya LJTL (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. 390:457-468[2]Taylor PC, Keystone EC, van der Heijde D et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376:652-662[3]Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Zhou Y, Othman AA (2018) A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ARTHRITIS & RHEUMATOLOGY. WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, pp[4]Combe B, Kivitz A, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J (2019) LB0001 EFFICACY AND SAFETY OF FILGOTINIB FOR PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO METHOTREXATE: FINCH1 PRIMARY OUTCOME RESULTS. BMJ Publishing Group Ltd, ppDisclosure of Interests:None declared

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