Background Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals. Objective To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naïve to tumor necrosis factor inhibitor therapy (TNFi-naïve) or with an inadequate response (TNFi-IR). Methods A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, ≥75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes. Results The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naïve patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naïve and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naïve or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naïve patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable). Conclusions Tofacitinib p...
BackgroundTofacitinib is an oral JAK inhibitor for the treatment of psoriatic arthritis (PsA).ObjectivesTo perform a systematic literature review (SLR) and network meta-analysis (NMA) to evaluate the efficacy of tofacitinib 5 and 10 mg BID relative to biologic disease-modifying antirheumatic drugs (bDMARDs) or a targeted synthetic DMARD (apremilast [APR]) in tumour necrosis factor inhibitor-naïve (TNFi-N) patients with active PsA.MethodsThe SLR identified randomised controlled clinical trials (RCTs) evaluating tofacitinib, bDMARDs or APR to treat patients with active PsA who were TNFi-N. Outcomes included American College of Rheumatology (ACR)20 response and change from baseline in Health Assessment Questionnaire-Disability Index (ΔHAQ-DI), Dactylitis Severity Score (ΔDSS) and Leeds Enthesitis Index (ΔLEI). Treatment effects were only evaluated during placebo (PBO)-controlled trial phases. The Bayesian NMA (with non-informative priors) was conducted using WinBUGs. The binomial logit model was used for ACR20. ΔHAQ-DI, ΔDSS and ΔLEI were analysed using the normal identify link model. A fixed-effect model was fitted to the data. Median treatment rankings represent data from each iteration of the model from which inferences are based, following model convergence.ResultsThe SLR identified 25 RCTs and 21 were included in the NMA (see treatments in table 1). All trials allowed methotrexate use. PBO-controlled treatment durations ranged from 12–24 weeks. In general, patient characteristics were similar across trials. All treatments were associated with improvements in ACR20 and ΔHAQ-DI vs PBO. Tofacitinib 5 mg BID was associated with substantially decreased odds ratios (ORs) for ACR20 vs golimumab 50 and 100 mg Q4W, etanercept 25 mg BW, infliximab 5 mg/kg and secukinumab 150 mg QW-Q4W (table 1); ORs for all remaining comparators were not substantially different. Tofacitinib 10 mg BID was associated with a substantially increased OR for ACR20 vs APR 20 mg BID. Etanercept was associated with an improvement in ΔHAQ-DI vs tofacitinib 5 and 10 mg BID. There was no difference in ΔHAQ-DI for tofacitinib vs other bDMARDs. For ACR20, tofacitinib 5 and 10 mg BID were median ranked 14 (95% credible interval: 8, 17) and 9,5, 14 respectively, among 18 comparators. For ΔHAQ-DI, tofacitinib 5 and 10 mg BID were median ranked 114, 13 and 8,2, 13 respectively, among 14 comparators. Two studies evaluated ΔDSS and ΔLEI; there were no substantial differences in ΔDSS and ΔLEI for tofacitinib 5 and 10 mg BID vs adalimumab 40 mg Q2W and ixekizumab 80 mg Q2W and Q4W.Abstract THU0300 – Table 1Fixed-effect NMA data for ACR20 and ΔHAQ-DI in TNFi-N patients with PsA – comparison of bDMARDs or apremilast vs tofacitinib 5 and 10 mg BIDa,bConclusionsBased on the NMA of published RCTs in TNFi-N patients with PsA, tofacitinib 5 and 10 mg BID had similar efficacy vs many, but not all, bDMARDs and APR in improving ACR20 and ΔHAQ-DI.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by P Scutt of CMC and funded by Pfizer Inc...
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