Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta‐analysis

Abstract

Background The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. Objectives To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. Methods We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10-16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. Results We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10-16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short-term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short-term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. Conclusions Using our methodology we found that most biologics cluster together with respect to short-term efficacy and tolerability, and we did not identify any

Comparative Efficacy and Relative Ranking of Biologics and Oral Therapies for Moderate-to-Severe Plaque Psoriasis: A Network Meta-analysis

“…For example, Sbidian et al [ 15 ] suggested that anti-IL-17 agents (ixekizumab, secukinumab, bimekizumab, and brodalumab), anti-IL-23 agents (risankizumab and guselkumab), and infliximab were significantly more effective, in terms of PASI 90 response rates, than ustekinumab and other anti-TNF agents (adalimumab, certolizumab, and etanercept). Mahil et al [ 13 ] showed that in terms of achieving clear/nearly clear skin status, ixekizumab was associated with the highest SUCRA value followed by risankizumab. Sawyer et al [ 12 ] reported that the anti-IL-17 agents guselkumab and risankizumab were more efficacious than tildrakizumab, ustekinumab, anti-TNF agents, and non-biologic systemic treatments.…”

“…While several recent network meta-analyses (NMAs) have been conducted to compare the relative efficacy of treatments for moderate-tosevere plaque psoriasis, knowledge gaps still exist [12][13][14][15][16][17][18][19]. First, PASI 100 results were not available in some of the recent NMAs [13,15]. Second, such NMAs may lack sufficient statistical power to detect potential differences between treatments with the highest PASI 90 and 100 response rates.…”

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

“…Agents targeting the IL-23/Th17 pathway have led to high hurdle responses in psoriasis, in excess of those seen with TNF inhibitors, 3 4 confirming the key pathogenetic role of IL-23/Th17 in the skin in psoriasis. By contrast, in PsA, there are limited head-to-head studies 5 6 and effects of treatment on joints appear more heterogeneous than in the skin.…”

Methotrexate vs secukinumab safety in psoriasis patients with metabolic syndrome

“…showing a neutral effect on the principal metabolic parameters. 8 The objective of the study was to compare the safety of methotrexate vs secukinumab in psoriasis patients with metabolic syndrome.…”

“…Studies investigating the safety profile in psoriasis patients with concomitant metabolic syndrome treated with methotrexate are scarce 7 . Secukinumab is a fully human monoclonal antibody that selectively blocks IL‐17A showing a neutral effect on the principal metabolic parameters 8 …”