Biologics for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-analysis

Abstract

Introduction: Moderate-to-severe plaque psoriasis is a chronic disease impacting quality of life (QoL). This network meta-analysis (NMA) compared efficacy and safety of all biologics approved for the treatment of moderate-to-severe plaque psoriasis to better inform providers on mid-term outcomes, with a focus on the interleukin-23 p19 inhibitor tildrakizumab.

Methods: MEDLINE®, Embase, and CENTRAL were searched for randomized clinical trials (RCT) from inception through January 2024. RCTs comparing biologics against placebo or each other reporting Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) 0/1, or Dermatology Life Quality Index (DLQI) 0/1 responses and safety outcomes (adverse events [AEs] or serious AEs [SAEs]) were sought. Bayesian NMAs were performed at week 28 as the primary time point of interest. Analyses were also performed at weeks 12 and 16. Findings were expressed as risk ratios (RR; efficacy outcomes), risk differences (RD; safety outcomes), and numbers needed to treat (NNT) with 95% credible intervals.

Results: Of 7418 publications screened, 187 describing 124 RCTs of 12 biologics were included in the systematic literature review, and 103 RCTs were included for NMA. All treatments demonstrated improved efficacy and QoL vs. placebo at week 28. Tildrakizumab efficacy at week 28 was comparable to risankizumab and guselkumab, respectively, for PASI 75 (RR 8.74 vs. 8.92 and 8.91), PASI 90 (RR 14.09 vs. 14.81 and 14.77), and PGA 0/1 (RR 9.34 vs. 10.29 and 10.23). No biologics exhibited an increased risk of SAEs vs. placebo; tildrakizumab exhibited no increased risk vs. placebo for AEs.

Conclusions: The investigated biologics demonstrated improved efficacy and QoL relative to placebo at week 28, with no increased risk of SAEs vs. placebo through week 16. At week 28, efficacy of tildrakizumab, risankizumab, and guselkumab was comparable. Limitations include lack of placebo comparators after week 12 or 16, which could affect results.

Keywords: Biologics; Network meta-analysis; Psoriasis; Systematic review; Tildrakizumab.

Fig. 1

Study selection process

Fig. 2

Network diagram of included trials and comparisons. A network diagram depicting the totality of RCTs included in the review (N = 103 studies) is shown above. Edges are proportionately sized to reflect the relative numbers of studies informing each treatment comparison. The structure of the network and the number of included RCTs per NMA varied according to the availability of data per study. ADA adalimumab, BIM bimekizumab, BIW twice weekly, BRO brodalumab, CZP certolizumab pegol, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, Q#W every # weeks, QW once weekly, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab

Fig. 3

Forest plot of NNTs vs. placebo for PASI 75/90/100 at week 28. Estimates of the NNT derived from random effects NMAs adjusted for placebo group response are presented for all interventions at week 28 for PASI 75, 90, and 100 response. Values of NNT closer to 1 are indicative of preferred interventions. Interventions are sorted in terms of increasing magnitude of NNT for PASI 75 response. *Statistically significant vs. placebo. ADA adalimumab, BIM bimekizumab, BIW twice weekly, BRO brodalumab, CrI credible interval, CZP certolizumab pegol, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, NNT number needed to treat, PASI Psoriasis Area and Severity Index, Q#W every # weeks, QW once weekly, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab

Fig. 4

Forest plot of NNTs vs. placebo for PGA 0/1 and DLQI 0/1 at week 28. Estimates of the NNT derived from random effects NMAs adjusted for placebo group response are presented for all interventions at week 28 for PGA 0/1 and DLQI 0/1 response. Values of NNT closer to 1 are indicative of preferred interventions. Interventions are sorted in terms of increasing magnitude of NNT for PASI 75 response as per Fig. 3 for consistency. *Statistically significant vs. placebo. ADA adalimumab, BIM bimekizumab, BIW twice weekly, BRO brodalumab, CrI credible interval, CZP certolizumab pegol, DLQI Dermatology Life Quality Index, ETN etanercept, GUS guselkumab, IFX infliximab, IXE ixekizumab, NNT number needed to treat, PGA Physician Global Assessment, Q#W every # weeks, QW once weekly, RIS risankizumab, SEC secukinumab, TIL tildrakizumab, UST ustekinumab