Comparative efficacy and safety of targeted DMARDs for active psoriatic arthritis during induction therapy: A systematic review and network meta-analysis

Objective: To summarize and investigate the comparative efficacy and safety of targeted disease-modifying antirheumatic drugs (DMARDs) for active psoriatic arthritis (PsA). Methods: Randomized clinical trials (RCTs) evaluating efficacy and safety of targeted synthetic DMARDs (tofacitinib, apremilast) as well as biological DMARDs (guselkumab, ustekinumab, secukinumab, ixekizumab, brodalumab, clazakizumab, abatacept, adalimumab, etanercept, infliximab, certolizumab, and golimumab) were identified by systemic literature review. Traditional meta-analysis and network meta-analysis using a random effects model were performed to estimate pooled odds ratios (OR) and 95% CI to compare and rank these treatments according to ACR20 response, 75% improvement in psoriasis area and severity index (PASI75), numbers of adverse events (AE) and serious adverse events (SAE). Similar analyses were conducted among biologic-naive population and biologic-experienced/failed population. Results: We deemed 29 RCTs eligible, including 10,204 participants and 17 treatments. During induction therapy (first 12-16 weeks), all treatments except clazakizumab were more efficacious than placebo in achieving ACR20 and PASI75. Although tofacitinib, apremilast, and ixekinumab 80 mg every 2 weeks had a higher rate of AE, no significant difference was revealed for SAE among all treatments. Network meta-analysis demonstrated that infliximab, golimumab, etanercept, adalimumab, guselkumab, and secukinumab 300 mg outperformed other drugs in achieving both ACR20 and PASI75. Infliximab, guselkumab, adalimumab, golimumab, secukinumab (300 mg and 150 mg), and ustekinumab (45 mg and 90 mg) are characterized by both high efficacy and safety. Similar rankings were observed in the analysis among biologic-naive patients. Moreover, ustekinumab, secukinumab (300 mg and 150 mg), ixekizumab, abatacept, certolizumab pegol, tofacitinib, and apremilast were still associated with higher ACR20 compared to placebo while ustekinumab, secukinumab (300 mg), ixekizumab and tofacitinib with higher PASI75 among biologic-experienced/failed patients. Conclusion: Regarding the overall risk-benefit profile, infliximab, guselkumab, adalimumab, golimumab, secukinumab, and ustekinumab may be safer and more efficacious treatments than the other targeted DMARDs for active PsA during induction therapy. (C) 2019 Elsevier Inc. All rights reserved.