Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab

Abstract

SummaryBackground Head-to-head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available. Objectives To assess efficacy and quality of life using matching-adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab. Methods Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis. Results In the meta-analysis of studies with active comparators, PASI 90 response rates were 12Á7% [95% confidence interval (CI) 5Á5-19Á8, P = 0Á0005], 10Á0% (95% CI 2Á1-18Á0, P = 0Á01) and 11Á2% (95% CI 3Á2-19Á1, P = 0Á006) higher and PASI 100 response rates were 11Á7% (95% CI 5Á9-17Á5, P < 0Á001), 12Á7% (95% CI 6Á0-19Á4, P < 0Á001) and 13Á1% (95% CI 6Á3-19Á9, P < 0Á001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly. Conclusions Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons.

Ixekizumab or secukinumab in psoriasis: what difference does it make?

“…In this issue of the BJD , Warren and colleagues present a systematic review and meta‐analysis indirectly comparing the efficacy of two interleukin (IL)‐17 antibodies, ixekizumab and secukinumab, in psoriasis . In collaboration with scientists from Eli Lilly, they show that ixekizumab has greater efficacy than secukinumab at 12 weeks when phase III data for both drugs are analysed with various meta‐analysis methods.…”

“…In conclusion, IL‐17 antagonists allow many patients to become free or almost free of psoriasis in the short term. Warren and colleagues provide substantial evidence that among IL‐17 antagonists, ixekizumab has a greater short‐term efficacy than secukinumab . It remains to be shown if this translates to better long‐term persistence in clinical practice and in sustained benefits for patients.…”

Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses

“…Biologic therapies have transformed the treatment of moderate-to-severe psoriasis and have markedly improved multiple patient outcomes [3,4]. Several biologics are available, including inhibitors of interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor (adalimumab, certolizumab pegol, etanercept, infliximab) [5,6].…”

Combination of several matching adjusted indirect comparisons (MAICs) with an application in psoriasis

“…Note that from the studies included in the etanercept bridge network, another placebo bridge network was also available. However, as discussed previously, placebo response rates are very low (nearly zero) across studies and are therefore noninformative, and low responses in this group make confidence intervals around the odds ratios unstable and difficult to interpret. Moreover, combination of the placebo bridge network with the etanercept bridge network is not possible since our method assumes independent networks.…”