Treatment with bimekizumab is associated with rapid and sustained improvements in outcomes of disease activity measures, with a favorable safety profile, in patients with active ankylosing spondylitis (AS), according to study results published in Annals of the Rheumatic Diseases.1
Proinflammatory interleukin (IL)-17A and IL-17F levels are elevated in patients with AS and may be neutralized by the monoclonal antibody bimekizumab.2 In this phase 2b randomized double-blind controlled trial (BE AGILE study; ClinicalTrials.gov Identifier: NCT02963506), the researchers aimed to evaluate the safety and efficacy of bimekizumab in patients with active AS.
A total of 303 patients with AS (84.5% men) were randomly assigned to receive bimekizumab (16, 64, 160, or 320 mg) or placebo every 4 weeks. After 12 weeks, patients receiving placebo or 16 or 64 mg of bimekizumab were reassigned 1:1 to receive 160 or 320 mg every 4 weeks until week 48. The primary efficacy end point was the percentage of patients with an Assessment of SpondyloArthritis International Society 40 response (ASAS40) at week 12. Secondary efficacy end points included several other indices of AS status and quality of life metrics.
Results showed that more patients achieved ASAS40 at 12 weeks in the 16 mg (29.5%; odds ratio [OR], 2.6; 95% CI, 1.0-6.5), 64 mg (42.6%; OR 4.5; 95% CI, 1.8-10.9), 160 mg (46.7%; OR, 5.5; 95% CI, 2.3-13.5), and 320 mg bimekizumab groups (45.9%; OR, 5.3; 95% CI, 2.2-12.9; P <.05) vs placebo (13.3%). Rapid responses to bimekizumab were seen among all groups, with 8.2% to 19.7% of patients achieving ASAS40 at week 1 and 16.4% to 50.8% at week 4; ASAS40 was achieved in 0% and 8.3% of patients in the placebo group at weeks 1 and 4, respectively.
The ASAS40 response rate continued to increase after the initial 12 weeks of treatment. At 48 weeks, ASAS40 was achieved in 58.6% and 62.3% of patients in the 160 mg and 320 mg bimekizumab groups, respectively. Of the patients initially assigned to the placebo group, 54.2% and 50.0% achieved ASAS40 at 48 weeks after reassignment to the bimekizumab 160 and 320 mg groups, respectively.
All secondary efficacy end points were in agreement with the ASAS40 response rates at 12 and 48 weeks.
Adverse events were reported by 37.9% of patients treated with bimekizumab during the initial 12 weeks compared with 43.3% in the placebo group. Over the course of the full trial, 77.6% of patients reported adverse events while receiving bimekizumab. The most frequently reported adverse events in ≥10% of patients were nasopharyngitis (11.2%) and hepatic events (13.6%). There was no relationship between the type or frequency of adverse events and bimekizumab dose.
Investigators noted that the relatively short placebo-controlled period (12 weeks) and small treatment group sizes represented a limitation of the study. In addition, the majority of participants were white (98.3%), which may have limited the generalizability of results to other populations.
“In summary, bimekizumab may provide a promising therapeutic option for patients with AS,” the researchers concluded. “Bimekizumab treatment resulted in rapid and sustained improvements across multiple outcomes of disease activity, [quality of life], and function.”
Disclosure: This study was funded by UCB Pharma. Several authors reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
1. van der Heijde D, Gensler LS, Deodhar A, et al. Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2020;79(5):595-604.
2. Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991-1001.