Interleukin-17 A/F Inhibitor vs Interleukin-17 Receptor Blocker: The Tale of the Sponge and the Plug

Abstract

Introduction Brodalumab (BRO) and bimekizumab (BIM) are treatments for moderate-to-severe psoriasis with distinct mechanisms of action. BRO, an interleukin (IL)-17 receptor A antagonist, selectively binds and inhibits receptor interactions with cytokine IL-17 isoforms A, C, E, and F. BIM, an IL-17A and -17F antagonist, selectively binds circulating IL-17A/F to inhibit IL-17 receptor complex interaction. Thus, BRO acts as a plug, binding to the receptor, whereas BIM acts as a sponge, attaching to circulating cytokines. As there are no head-to-head trials, we present clinical profile comparisons to assist clinicians in understanding key differences between BRO and BIM.

Methods Data were extracted from clinical , network meta-analyses (NMAs) of clinical trials, prescribing information, and real-world studies. Precedence was given to studies providing comparisons between BRO and BIM.

Results A retrospective study reported nonsignificant differences at week 36 between BRO and BIM, respectively, in 90% improvement from baseline in psoriasis area and severity index (PASI 90; 76% vs 83%) and PASI 100 (67% vs 74%). Likewise, an NMA reported similar efficacy vs placebo in PASI 90 risk ratios (RRs) at week 28 (BRO, 13.98; BIM, 14.76). However, 2 NMAs reported superior PASI 90 for BIM vs BRO. Regarding onset of action, a retrospective study reported that BRO vs BIM had significantly lower PASI 100 (P<0.05), but not PASI 90 rates (P≥0.05), at week 4. Additionally, an NMA reported similar average times to achieve PASI 90 for BRO and BIM (46.7 vs 41.5 days). Phase 3 trial post hoc analyses reported higher PASI 100 rates with BIM in patients with prior biologic exposure (BIM, 72% [week 156]; BRO, 50%-55% [week 120]). Specialized psoriasis treatment comparisons were limited by inconsistent endpoints. Still, for nail psoriasis, an NMA reported higher probability of achieving complete resolution at weeks 24-28 with BRO (37%) vs BIM (30%). For safety results, a retrospective study of BRO vs BIM reported fewer eczematous reactions (0 vs 2) and candidiasis cases (1 vs 4). Candidiasis rates were lower for BRO vs BIM in pharmacovigilance reports (<1% vs 9%) and prescribing information (<1% vs 10% [mostly oral candidiasis]), and an NMA reported lower infection RR with BRO (1.15) vs BIM (1.36). BRO inhibits more IL-17 cytokines than BIM (A/C/E/F vs A/F, respectively). BRO (210 mg) is given as subcutaneous injection (SC) at weeks 0, 1, and 2, with maintenance dosing every 2 weeks. BIM (320 mg) is given SC at weeks 0, 4, 8, 12, and 16, with maintenance every 8 weeks and considerations for every 4 weeks in patients weighing ≥120 kg.

Conclusions Studies demonstrate comparable efficacy and onset of action between BRO and BIM, with some favoring BIM. Increased rates of eczematous eruptions and fungal infections are associated with BIM. Balanced decision-making that considers efficacy and adverse events is warranted when choosing between BRO and BIM.