Comparative effectiveness of abatacept, apremilast, secukinumab and ustekinumab treatment of psoriatic arthritis: a systematic review and network meta-analysis

To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis factor alpha (TNF-alpha) biologic drugs in the treatment regimen of the disease. A systematic review and network meta-analysis (NMA) was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) requirements. Two investigators identified the studies, abstracted data, and assessed the risk of bias independently. The NMA was conducted for efficacy [American College of Rheumatology (ACR) criteria, ACR20 and ACR50; psoriasis area and severity index (PASI), PASI75] and safety outcomes [any adverse events (AEs) and serious adverse events (SAEs)]; treatments were ranked using the P score for each outcome. The PROSPERO registration number was 42017072200. MEDLINE/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from the inception of each database to July 10, 2017. Randomized controlled trials (RCTs) for abatacept, apremilast, secukinumab or ustekinumab in adults with moderate and severe PsA were included. The overall PsA population and anti-TNF-alpha-naive, anti-TNF-alpha-failure, or anti-TNF-alpha-experienced subpopulations were considered. We identified eight eligible RCTs and included them in the systematic review and NMA. Significant differences in ACR20 response rate were revealed between secukinumab 150 mg and apremilast 20 mg [relative risk; RR = 2.55 (CI-confidence interval; 1.24, 5.23)] and between secukinumab 300 mg and apremilast 20 or 30 mg [RR = 3.57 CI (1.48, 8.64) and RR = 2.84 CI (1.18, 6.86), respectively]. Any AEs occurred more often in apremilast 20 and 30 mg compared with placebo [RR = 0.58 CI (0.45, 0.74) and RR = 0.58 CI (0.45, 0.75), respectively] but also compared with secukinumab 150 mg [RR = 0.54 CI (0.35, 0.81) and RR = 0.45 CI (0.35, 0.82), respectively]. No significant differences were revealed for SAEs among biologics and between biologics and placebo. In the overall population, as well as in the anti-TNF-alpha-naive subpopulation, secukinumab at a dose of 300 and 150 mg was ranked the highest for the ACR20 endpoint, while in the anti-TNF-alpha-experienced subpopulation, secukinumab 300 mg and apremilast 30 mg revealed the highest rank. Secukinumab 75 mg was the safest drug in terms of any AEs, but for SEAs the safest was ustekinumab 90 mg. Our study revealed no significant differences among non-anti-TNF-alpha biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any AEs, and ustekinumab 90 mg presented the lowest overall risk of SAEs. Head-to-head trials and evaluation of comparative efficacy and safety between non-TNF-alpha biologics are warranted to inform clinical decision making with a relevant treatment paradigm.