How safe is long-term bimekizumab in plaque psoriasis patients?

Treatment with bimekizumab (BKZ) for over 3 years does not result in the occurrence of new adverse events (AEs), demonstrating its positive safety profile in patients with moderate-to-severe plaque psoriasis, as shown by a pooled analysis of five phase III/IIIb trials presented at EADV 2023.

In addition, longer exposure to BKZ does not lead to an increase in exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs).

“Since psoriasis is a chronic disease, assessment of long-term safety of psoriasis treatments is essential to inform clinical decision-making and to manage risks for patients,” said the investigators, led by Dr Mark Lebwohl, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, US. [Psoriasis (Auckl) 2022;12:1-14]

“Data pooled over 2 years have shown that BKZ, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL17A, is well-tolerated in the treatment of moderate to severe plaque psoriasis,” they added. [Front Immunol 2020;11:1894; JAMA Dermatol 2022;158:735-744]

In this study, Lebwohl and his team pooled data from the BE SURE, BE VIVID, and BE READY trials, the ongoing open-label extension BE BRIGHT (data cutoff: 23 October 2021), and the ongoing BE RADIANT phase IIIb trial (data cutoff: 6 May 2022). [N Engl J Med 2021;385:130-141; Lancet 2021;397:487-498; Lancet 2021;397:475-486; N Engl J Med 2021;385:142-152; clinicaltrials.gov/ct2/show/NCT03598790]

Eligible participants were administered BKZ 320 mg every 4 weeks (Q4W) or every 8 weeks (Q8W), all of whom received BKZ Q8W from week 64 (BE RADIANT) or week 100/104 (BE BRIGHT), or the next scheduled clinical visit.

The investigators assessed 3-year TEAEs using EAIRs per 100 patient-years for all participants who received at least one BKZ dose. They also reported data separately for year 1 (week 0‒52), 2 (week >52‒104), and 3 (week >104‒156) of exposure to BKZ.

Overall, 2,186 patients had a total BKZ exposure of 5,461.4 patient-years (year 1: 2,104.6 patient-years, n=2,186; year 2: 1,905.2 patient-years, n=1,962; year 3: 1,316.9 patient-years, n=1,547). [EADV 2023, abstract 242]

TEAEs arose at an EAIR of 174.4 per 100 patient-years, serious TEAEs at 5.6 per 100 patient-years, and TEAEs leading to discontinuation at 3.1 per 100 patient-years. Longer BKZ exposure did not lead to an increase in EAIRs. Of note, 21 deaths occurred over the 3-year period, but none were treatment-related.

Oral candidiasis

Patients treated with BKZ Q8W had lower overall rates of TEAEs, particularly Candida infections, compared with those who received BKZ Q4W. Nasopharyngitis (14.1 per 100 patient-years) was the most common TEAE, followed by oral candidiasis (10.0 per 100 patient-years) and upper respiratory tract infection (6.2 per 100 patient-years).

Nearly all oral candidiasis infections were mild or moderate in severity (99.1 percent), and only a few patients with oral candidiasis ceased treatment (1.7 percent).

On the other hand, serious infections occurred at an EAIR of 1.3 per 100 patient-years. The most common serious infection was coronavirus infection (0.3 per 100 patient-years). No active tuberculosis case had been reported.

“EAIRs of laboratory elevations in aspartate aminotransferase or alanine aminotransferase >3 and >5 times the upper limit of normal were 2.0 and 0.5 per 100 patient-years, respectively, and did not increase with longer BKZ exposure,” the investigators said.

“EAIRs of adjudicated inflammatory bowel disease (0.2 per 100 patient-years), major adverse cardiac events (0.5 per 100 patient-years), and suicidal ideation and behaviour (0.1 per 100 patient-years) were low,” they added.