Efficacy and Safety of Bimekizumab in the Treatment of Moderate to Severe Plaque Psoriasis - BE READY Study Results

Targeting IL-17

Within the interleukin 17 family, IL-17A and IL-17F play a key role in the pathogenesis of psoriasis. Inhibiting these two interleukins leads to a rapid and significant reduction in clinical symptoms in patients with plaque psoriasis. IL-17A inhibitors are characterized by a fast onset of action, although, according to recent comparative studies, maintaining the therapeutic response may not be as robust compared to IL-23 inhibitors.

Available evidence suggests that simultaneous inhibition of IL-17A and IL-17F may offer a more effective therapeutic response compared to the inhibition of IL-17A alone, while avoiding the undesired broader blockade of the IL-17RA receptor.

Bimekizumab is a humanized monoclonal IgG1 antibody that selectively binds with high affinity to the IL-17A, IL-17F, and IL-17AF cytokines, representing a promising therapeutic modality for adult patients with moderate to severe plaque psoriasis where systemic treatment is indicated.

Study Methodology, Course, and Goals

The multicenter randomized double-blind placebo-controlled phase III clinical trial, BE READY, was conducted in 77 centers across 9 countries on different continents. Patients older than 18 years with moderate to severe plaque psoriasis were included, stratified by region and prior exposure to biologics, and then randomized in a 4:1 ratio to receive bimekizumab at a dose of 320 mg every 4 weeks or placebo every 4 weeks.

The study's co-primary goals were to assess the proportion of patients achieving ≥ 90% improvement in the Psoriasis Area Severity Index (PASI90) and the proportion of patients achieving a score of 0 (clear) and 1 (almost clear) on a 5-point Investigator's Global Assessment (IGA) scale at week 16 of therapy. Participants who achieved PASI90 at week 16 were reallocated in a 1:1:1 ratio to receive bimekizumab 320 mg every 4 weeks, every 8 weeks, or placebo for the next 40 weeks (up to week 56 of therapy).

Findings

From February 5, 2018, to January 7, 2020, a total of 435 patients were enrolled in the study, of which 349 were randomized to bimekizumab and 86 to placebo. Baseline demographic and initial characteristics were similar in both groups. The treatment discontinuation rate was comparably low in both groups.

PASI90 score was achieved at week 16 by 91% of patients on bimekizumab and only 1% on placebo (risk difference 89.8; 95% confidence interval [CI] 86.1–93.4; p < 0.0001). The IGA score of 0 and 1 was achieved by 93% of patients on bimekizumab and only 1% on placebo (risk difference 91.5; 95% CI 88.0–94.9; p < 0.0001).

Complete treatment response assessed by PASI100 was observed in 68% of patients on bimekizumab and 1% on placebo. An IGA score of 0 was recorded in 70% of patients on bimekizumab and 1% on placebo. At week 16 of therapy, a significant improvement in scalp psoriasis was observed in patients on bimekizumab compared to placebo. Objective clinical improvement was supported by similar improvements in patient-reported outcomes.

A similar therapeutic response was subsequently maintained up to week 56 of therapy in both bimekizumab dosing regimens. The median time to disease relapse characterized by PASI < 75 in patients reallocated at week 16 to placebo was 28 weeks (95% CI 24–32; p < 0.0001; 32 weeks from the last dose of bimekizumab).

Treatment-related adverse events occurred in 61% of patients on bimekizumab and 41% on placebo during the initial period (up to week 16 of therapy). In the therapeutic period after patient reallocation, they were observed in 74% of patients on bimekizumab every 4 weeks, 77% on bimekizumab every 8 weeks, and 69% on placebo. The most common adverse events (> 5%) were nasopharyngitis, oral candidiasis, and upper respiratory tract infections. Serious adverse events were rare, leading to treatment discontinuation in a minimal number of cases, and no deaths were observed during the study.

Conclusion

In the BE READY study, bimekizumab demonstrated high clinical efficacy in the treatment of moderate to severe plaque psoriasis. The high therapeutic response rate was maintained for up to 56 weeks of therapy in both dosing regimens. Bimekizumab was well tolerated by patients in the study, consistent with the known safety profile to date.

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Source: Gordon K. B., Foley P., Krueger J. G. et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicenter, double-blind, placebo-controlled, randomized withdrawal phase 3 trial. Lancet 2021; 397 (10273): 475–486, doi: 10.1016/S0140-6736(21)00126-4.