Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: Results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial

J Am Acad Dermatol. 2018 Aug;79(2):277-286.e10. doi: 10.1016/j.jaad.2018.03.037. Epub 2018 Mar 30.

Abstract

Background: Neutralizing interleukin (IL) 17F in addition to IL-17A might provide a more complete and specific approach to inhibiting inflammation.

Objective: Assess the efficacy and safety of bimekizumab, a monoclonal antibody that potently and selectively neutralizes IL-17A and IL-17F, in patients with moderate-to-severe plaque psoriasis.

Methods: Double-blinded, placebo-controlled phase 2b study (NCT02905006). Patients (randomized 1:1:1:1:1:1) received subcutaneous bimekizumab every 4 weeks at doses of 64 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, 480 mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at week 12.

Results: There was a significant (P < .0001) dose-dependent response for PASI90 (week 12); more patients achieved PASI90 in the bimekizumab groups (46.2%-79.1%) than patients in the placebo group (0%; P < .0001 all doses). Across all doses, there were significant improvements from baseline for all secondary endpoints (PASI90 week 8, PASI75 week 12, PASI100 week 12, and Investigators Global Assessment clear or almost clear weeks 8 and 12; P ≤ .0003) compared with placebo. More bimekizumab-treated patients than placebo-treated patients achieved PASI100 (week 12) (27.9%-60.0% vs 0%; P ≤ .0002 all doses). Treatment-emergent adverse events were reported by 126 of 208 (61%) bimekizumab-treated patients and 15 of 42 (36%) placebo-treated patients.

Limitations: No active comparator.

Conclusion: Dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings.

Keywords: PASI100; PASI90; anti-IL-17; anti-IL-17A; anti-IL-17F; bimekizumab; biologic therapy; clear or almost clear skin; dose ranging; efficacy; interleukin 17A; interleukin 17F; phase 2b; plaque psoriasis; randomized clinical trial; safety.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Chronic Disease
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interleukin-17 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / immunology*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Dermatologic Agents
  • IL17A protein, human
  • IL17F protein, human
  • Interleukin-17
  • bimekizumab