Number Needed to Treat Network Meta-Analysis to Compare Biologic Drugs for Moderate-to-Severe Psoriasis

Abstract

Introduction: Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT.

Methods: The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12.

Results: Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12.

Conclusions: Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.

Keywords: Biologics; Meta-analysis; NNT; Psoriasis.

Fig. 1

Evidence network for NMA of PASI 90 at week 12. A total of 35 RCTs and 20 treatments are included. Lines represent direct comparisons using RCTs (n). Numbers and thicknesses of lines represent the number of RCTs included in each comparison (N). ^a200 mg at Weeks 0 and 4, then every 12 weeks; ^b100 mg at Weeks 0 and 4, then every 12 weeks; ^c100 mg at Weeks 0 and 4, then every 8 weeks; ^d80 mg at Week 0, 40 mg at week 1, then 40 mg Q2W. ADA adalimumab (anti-TNF agent), BIW twice weekly, BRO brodalumab (anti-IL-17 agent), CZP certolizumab pegol (anti-TNF agent), ETN etanercept (anti-TNF agent), GUS guselkumab (anti-IL-23 agent), IFX infliximab (anti-TNF agent), IXE ixekizumab (anti-IL-17 agent), NMA network meta-analysis, PASI Psoriasis Area and Severity Index, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, Q12W every 12 weeks, RCT randomized controlled trial, RIS risankizumab (anti-IL-23 agent), SEC secukinumab (anti-IL-17 agent), TIL tildrakizumab (anti-IL-23 agent), UST ustekinumab (anti-IL-12/-23 agent)

Fig. 2

NNT to achieve PASI 90 and PASI 100 responses at weeks 12, 16, and 48/52. Data are mean relative to placebo. Missing data are marked NA. Studies included in the analysis are listed in the Supplementary Material. ADA adalimumab, BRO brodalumab, Crl credible interval, CZP certolizumab pegol, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, NA not applicable, NNT number needed to treat, PASI Psoriasis Area and Severity Index, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab

Fig. 3

Treatment effects on PASI 90 and 100 response rates at week 12, week 16, and week 48/52. Data are mean relative to placebo. Missing data are marked NA. Studies included in the analysis are listed in the Supplementary Material. ADA adalimumab, BRO brodalumab, CZP certolizumab pegol, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, NA not applicable, PASI Psoriasis Area and Severity Index, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab

Fig. 4

a Relative response of biologic treatments of moderate-to-severe plaque psoriasis based on BNMA for PASI 90 at week 48/52. b NNT to achieve PASI 90 at week 48/52. PASI 100 data are in panels (c) and (d). Missing data are marked NA. Studies included in the analysis from the studies are listed in the Supplementary Material. ADA adalimumab, BNMA Bayesian network meta-analysis, BRO brodalumab, Crl credible interval, CZP certolizumab pegol, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, NA not applicable, NNT number needed to treat, PASI Psoriasis Area and Severity Index, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab