Efficacy and safety of biologics targeting interleukin-6,-12/23 and-17 pathways for peripheral psoriatic arthritis: a network meta-analysis

To investigate the comparative efficacy, safety and tolerability of IL-6, IL-12/23 and IL-17 inhibitors for patients with active PsA. Randomized controlled trials evaluating the efficacy, safety and tolerability of IL-6, IL-12/23 and IL-17 inhibitors were identified by a comprehensive systematic literature review. Pairwise meta-analyses and Bayesian network meta-analyses using the random effects model were performed to estimate pooled odds ratios (ORs) and 95% credible intervals of attaining a 20% or 50% improvement in ACR criteria (ACR20 and ACR50, respectively) across trials. Six trials were identified that included 2411 participants and 11 treatments. Pairwise meta-analysis showed that secukinumab, ustekinumab and ixekizumab demonstrated superior efficacy over placebo in achieving an ACR20 and ACR50 response. However, ixekizumab has a higher incidence of adverse events (AEs) than placebo. In contrast, ustekinumab has a higher tolerability (less likely to be discontinued due to AEs) than placebo. Network meta-analysis showed that secukinumab (300 mg monthly) had the highest efficacy in achieving ACR20 and ACR50, whereas clazakizumab (200 mg monthly), ustekinumab (45 mg 12 weekly) and secukinumab (150 mg monthly) had the lowest probability of having AEs, serious AEs and intolerability, respectively. Considering the overall risk-benefit profile, secukinumab (150 mg monthly) may offer an optimal balance for peripheral PsA patients. Secukinumab may be the safest and most efficacious short-term treatment for peripheral PsA among all the new biologics targeting IL-6, IL-12/23 and IL-17 pathways.