Bimekizumab safety for moderate to severe plaque psoriasis affirmed

Treatment with bimekizumab for up to 2 years appears to be tolerated well in patients with moderate-to-severe plaque psoriasis, with no increased risk of adverse events (AEs) aside from a higher frequency of mild-to-moderate oral candidiasis, according to pooled analyses of data from eight randomized controlled trials (RCTs).

“Overall, the incidence of treatment-emergent AEs (TEAEs) decreased with a longer duration of bimekizumab exposure. In the phase III trials, the incidence of TEAEs was lower in patients treated with bimekizumab, 320 mg, Q8W compared with Q4W,” the investigators said. “The rate of discontinuation due to TEAEs was low.”

A total of 1,789 patients (mean age 45.2 years, 70.0 percent men) who received one or more doses of bimekizumab across four phase II (BE ABLE 1, BE ABLE 2, PS0016, PS0018) and four phase III RCTs (BE VIVID, BE READY, BE SURE, BE BRIGHT) were included in the analyses, with total treatment exposure of 3,109.7 person-years. The exposure-adjusted incidence rate (EAIR) of TEAEs was 202.4 per 100 person-years, and the frequency remained relatively unchanged with longer duration of bimekizumab exposure. [JAMA Dermatol 2022;158:735-744]

Nasopharyngitis was the most common TEAE, occurring at 19.1 per 100 person-years (95 percent confidence interval [CI], 17.4–20.9). This was followed by oral candidiasis (12.6 per 100 person-years, 95 percent CI, 11.3–14.0) and upper respiratory tract infection (8.9 per 100 person-years, 95 percent CI, 7.8–10.1). Most cases of oral candidiasis were mild or moderate, with three resulting in treatment discontinuation.

“Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both IL-17A and IL-17F… Interleukin-17 is involved in mucosal host defenses against fungal infections; therefore, anti–IL-17 biologics can be associated with an increased risk of oral mucocutaneous candidiasis,” the investigators pointed out. [Ann Rheum Dis. 2018;77:523-532; Front Immunol 2020;11:1894; Clin Rev Allergy Immunol 2018;55:379-390; Am J Clin Dermatol 2016;17:329-336; J Dermatol Sci 2021;101:145-146]

“The EAIR of oral candidiasis decreased with a longer duration of bimekizumab exposure and was lower with bimekizumab Q8W compared with Q4W,” they said.

Other events likewise infrequent

Meanwhile, patients with psoriasis can be at heightened risk of inflammatory bowel disease (IBD) and rare exacerbations have been reported with IL-17A inhibitors. Despite this, the EAIR of IBD in the pooled analyses was low at 0.1 per 100 person-years (95 percent CI, 0.0–0.3). [JAMA Dermatol 2018;154:1417-1423; J Invest Dermatol 2019;139:316-323; Br J Dermatol 2016;175:487-492; BMC Gastroenterol 2019;19:162]

Furthermore, the EAIR of adjudicated suicidal ideation and behaviour (SIB) was small and within the background rate for patients with psoriasis (0.0 per 100 person-years, 95 percent CI, 0.0–0.2)—a finding that the investigators found to be notable since psoriasis can place a substantial burden on the quality of life of patients who may, in turn, be at increased risk of depression and SIB. [J Immunol 2013;190:521-525; G Ital Dermatol Venereol 2019;154:56-63; Eur Acad Dermatol Venereol 2017;31:1168-1175]

Finally, the EAIR of major adverse cardiac events was nominal (0.5 per 100 person-years, 95 percent CI, 0.3–0.8).

One limitation of the study was that the patients included in the analyses might not fully represent a real-world population owing to the specific patient inclusion and exclusion criteria of the trials, according to the investigators. Additionally, they acknowledged that the population might be too small to draw definitive conclusions for more rare events.