Efficacy and safety of bimekizumab in patients with active PsA

Dual neutralisation of IL-17A and IL-17F with bimekizumab was linked to substantial improvements in both musculoskeletal and skin outcomes in patients with active psoriatic arthritis (PsA). Response rates increased after week 12 and were sustained from week 24 to 48. “Patients achieved similar ACR and PASI responses as compared with the overall study population. The safety profile of bimekizumab was consistent with previous reports, and bimekizumab is currently being evaluated in phase 3 trials” concluded Dr Christopher Ritchlin (University of Rochester Medical Centre, USA) [1].

Therapeutic options for psoriasis include biologic drugs such as tumour necrosis factor inhibitors (TNFi) and IL-12/23 inhibitors. Bimekizumab is a monoclonal antibody that selectively neutralises both, IL-17 homo-, and heterodimers,” said Dr Ritchlin. “The rationale for blocking both IL-17A and IL-17F is the recent discovery that both contribute to the development of PsA. IL-17A and IL-17F are different isoforms of IL-17 having structural homology and overlapping biological functions. Both are expressed in sites of inflammation and independently cooperate with other cytokines. The study objective was to assess the dose-response, long-term efficacy, and safety of bimekizumab over 48 weeks in patients with active PsA.

The randomised, double- and dose-blind, placebo-controlled, BE ACTIVE phase 2B trial included adult PsA patients (n=206), who had both ≥3 tender and ≥3 swollen joints and a CASPAR score ≥3. Patients were randomised (1:1:1:1:1) to receive subcutaneous bimekizumab 16 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, or placebo every 4 weeks, for a double-blind period of 12 weeks. After week 12, patients receiving placebo or bimekizumab 16 mg were re-randomised (1:1) to receive bimekizumab 160 mg or 320 mg for the remaining 36 weeks. All other patients continued on their initial dose (dose-blind period). The primary endpoint was the occurrence of disease worsening, defined by the disease-specific composite measures, including ACR criteria or PASI scores, or clinically significant worsening leading to a major change in treatment.

At baseline, the patients had an average tender joint count of 21.7, an average swollen joint count of 11.5, and 66.5% had a psoriasis body surface area of ≥3% or above. The dropout rate for the study was 8%.

The results showed that at week 12, significantly more patients receiving bimekizumab had achieved an ACR50 response, with rates of 26.8% at the 16 mg dose, 41.5% at the 160 mg dose, and 46.3% at the 160 mg dose + 320 mg loading dose, compared with 7.1% in the placebo group. The 24.4% ACR50 response rate in patients taking the 320 mg dose was not significantly different from placebo. “This may be due in part to this group having more active skin and joint disease than the other groups,” said Dr Ritchlin. By week 48, ACR50 response rates in the 320 mg dose group, including those re-allocated at 12 weeks, had improved in line with those of the other groups. PASI100 response rates among patients receiving bimekizumab ranged from 17.2% to 50.0% at week 12 vs 7.1% in those receiving placebo. These rates continued to increase, reaching up to 61% to 73% at week 48. The safety profile of bimekizumab was consistent with previous reports, with no apparent relationship between dose and treatment-emergent adverse events.

1. Ritchlin C. T. , et al. Abstract OP0108. EULAR 2019

Posted on 4 September 201916 February 2024