A pooled analysis of phase IIb/III clinical trials found low rates of uveitis in patients with axial spondyloarthritis treated with bimekizumab, a dual interleukin (IL)-17A and IL-17F inhibitor. 

In the study, published in Annals of the Rheumatic Diseases, researchers reported an exposure-adjusted incidence rate (EAIR) of 1.2 per 100 patient-years for uveitis events over 2034.4 patient-years of bimekizumab exposure. The analysis pooled data from patients receiving 160 mg of bimekizumab or placebo in the BE MOBILE 1 (nonradiographic axSpA) and BE MOBILE 2 (radiographic axSpA) phase III trials. Data were also pooled from patients treated with at least one bimekizumab dose in these trials and their open-label extensions as well as the phase IIb BE AGILE trial in radiographic axial spondyloarthritis (axSpA) and its extension.

In the 16-week double-blind treatment periods of two phase III trials (BE MOBILE 1 and 2), 0.6% (n = 2/349) of the patients receiving 160 mg of bimekizumab experienced uveitis compared with 4.6% (n = 11/237) of those receiving placebo (nominal P = .001). The EAIR was 1.8 per 100 patient-years (95% confidence interval [CI] = 0.2–6.7) for bimekizumab vs 15.4 per 100 patient-years (95% CI = 7.7–27.5) for placebo.

In the larger phase IIb/III pooled analysis (N = 848, exposure 2034.4 patient-years), 2.9% (n = 25/848) of bimekizumab-treated patients experienced a uveitis event. A total of 34 uveitis events occurred, with an exposure-adjusted event rate (EAER) of 1.7 per 100 patient-years. The EAIR was 4.6 per 100 patient-years (95% CI = 2.5–7.7) in those with a history of uveitis vs 0.6 per 100 patient-years (95% CI = 0.3–1.2) in those without.

The study population had a mean age of 40.3 years (standard deviation [SD] = 11.9), was 71.5% male, and 71.2% had radiographic axSpA. The mean time since first axSpA symptoms was 12.4 years (SD = 9.9). At baseline, 84.6% were HLA-B27 positive, 15.3% had a history of uveitis, and 12.7% had prior tumor necrosis factor (TNF) inhibitor exposure. The mean Ankylosing Spondylitis Disease Activity Score (ASDAS) was 3.8 (SD = 0.8), and the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 6.6 (SD = 1.3).

Concomitant medication use at baseline included conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in 23.2% of patients, nonsteroidal anti-inflammatory drugs (NSAIDs) in 81.3%, and corticosteroids in 8.3%.

In BE MOBILE 1 (nonradiographic axSpA), 1.6% (n = 2/128) of bimekizumab-treated patients had a uveitis event compared to 4.8% (n = 6/126) receiving placebo. In BE MOBILE 2 (radiographic axSpA), no patients treated with bimekizumab (n = 0/221) had a uveitis event, while 4.5% (n = 5/111) of those treated with placebo did.

All reported uveitis events were mild or moderate in severity. Only one event led to permanent discontinuation of bimekizumab. This event occurred 209 days after treatment initiation and was described as mild and intermittent.

A Kaplan-Meier analysis showed no clear trend in time from first bimekizumab administration to first uveitis event. For patients with a history of uveitis, the mean time since first diagnosis was 9.2 years (SD = 8.8), and the mean time since resolution of the last event was 3.9 years (SD = 6.5).

The researchers noted that while TNF inhibitors have demonstrated effectiveness in reducing uveitis rates in axSpA, evidence for IL-17 inhibition has been mixed. They hypothesized that dual inhibition of IL-17A and IL-17F with bimekizumab may provide more effective suppression of inflammation compared with IL-17A inhibition alone.

Limitations of the study included reliance on spontaneous adverse event reporting rather than systematic ophthalmologic assessments and the short placebo-controlled period (16 weeks), which limited long-term comparisons.

Conflict of interest disclosures can be found in the study.