Integrated trial analysis finds no new safety signals in axial spondyloarthritis and psoriatic arthritis.
Bimekizumab has maintained a consistent long-term safety profile in patients with axial spondyloarthritis and psoriatic arthritis, according to an updated pooled analysis of six phase 2b/3 clinical trials that extends follow-up to as much as five years of treatment exposure.
The integrated analysis combined safety data from the bimekizumab development program across the spondyloarthritis spectrum, including both core studies and their open-label extension phases.
Results have been published in the BMJ’s RMD Open Rheumatic & Musculoskeletal Diseases.
Bimekizumab, a monoclonal antibody that selectively inhibits both IL-17F and IL-17A, has shown superior efficacy to placebo in patients with axial spondyloarthritis and psoriatic arthritis and has generally been well tolerated across indications.
Previous integrated analyses of phase 2b/3 trials indicated a consistent and favourable safety profile across these patient populations.
Because both conditions are chronic, ongoing evaluation of long-term integrated safety data is important to confirm that bimekizumab maintains an acceptable safety profile over extended treatment periods, the researchers noted.
Their study added another year of data from ongoing phase 3 open-label extension studies and showed that bimekizumab maintained a consistent long-term safety profile in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).
In total, 848 patients with axial spondyloarthritis (axSpA) and 1409 patients with psoriatic arthritis (PsA) received at least one dose of bimekizumab 160mg every four weeks.
Cumulative exposure reached 2513.8 patient-years in axSpA and 3655.9 patient-years in PsA, providing a large dataset to assess longer-term tolerability.
Investigators reported broadly comparable safety outcomes between the two disease groups.
The exposure-adjusted incidence rate of treatment-emergent adverse events was 129.6 per 100 patient-years in axSpA and 126.9 per 100 patient-years in PsA.
Most adverse events were mild or moderate, and severe events were uncommon, occurring at rates of 3.2 and 3.5 per 100 patient-years respectively.
Discontinuations due to adverse events were infrequent, with exposure-adjusted rates of 2.4 per 100 patient-years in axSpA and 2.9 per 100 patient-years in PsA. Serious adverse events were also relatively uncommon, occurring at rates of 5.3 and 5.8 per 100 patient-years respectively.
The most commonly reported adverse events across the trials were covid-19 infection, nasopharyngitis and upper respiratory tract infection.
Serious infections were rare, with incidence rates of 1.4 per 100 patient-years in axSpA and 1.3 per 100 patient-years in PsA. Importantly, investigators reported no cases of active tuberculosis, histoplasmosis, coccidioidomycosis or blastomycosis during the study period.
Oral candidiasis remained one of the more frequently reported adverse events associated with IL-17 pathway inhibition, reflecting the role of IL-17 signalling in mucosal antifungal immunity.
However, most cases were mild or moderate and responded to standard antifungal treatment. Incidence rates were 3.5 per 100 patient-years in axSpA and 3.8 per 100 patient-years in PsA, with very few cases leading to treatment discontinuation.
The analysis also examined several safety topics of interest associated with biologic therapies, including hepatic events, inflammatory bowel disease, uveitis and major adverse cardiovascular events.
Incidence rates for these outcomes were low across both patient populations. For example, adjudicated major adverse cardiovascular events occurred at rates of 0.2 per 100 patient-years in axSpA and 0.3 per 100 patient-years in PsA.
Malignancies were reported in 1.2% of patients with axSpA and 1.7% of those with PsA, with similar exposure-adjusted incidence rates across both groups. There were no serious hypersensitivity or anaphylactic reactions reported in any of the included trials.
Related
Across the entire dataset, investigators recorded three deaths among patients with axSpA and five among those with PsA.
Two additional deaths occurred between the previous and current data cuts, due to cardiac arrest and hepatobiliary neoplasm, though investigators did not consider these events related to bimekizumab treatment.
Mental health outcomes were also assessed using validated patient-reported tools. Rates of suicidal ideation or behaviour were low across the trials, and there were no cases of completed suicide.
Depression scores measured using the PHQ-9 generally improved from baseline and remained stable during follow-up.
The researchers said the additional year of follow-up data from ongoing extension studies reinforced the consistent safety profile previously reported for bimekizumab and supported its longer-term use across the spondyloarthritis spectrum.
“It will be important to assess the safety profile across a more representative population of patients,” they noted.
“Additionally, future research should consider the safety profile in subgroups of patients that may have higher risk of AEs of interest. For example, methotrexate use has previously been found to be associated with an increased risk of liver-related AEs.
“Further, patients with both PsA and psoriasis have been found to be at higher risk for MACE.
“Although outside of scope for the current analysis, such subgroup analyses may warrant further exploration in the future. Real-world data should be collected to demonstrate the safety and tolerability of bimekizumab treatment in routine clinical practice.”
