The study explored the long-term safety and effectiveness of Bimekizumab (BKZ), a monoclonal antibody designed to block two proteins involved in inflammation, IL-17A and IL-17F. This dual inhibition helps control the excessive inflammation seen in ankylosing spondylitis (AS), a type of arthritis that primarily affects the spine and causes pain, stiffness, and reduced mobility.
This research included results from a five-year follow-up of patients who initially participated in a Phase 2b clinical trial called BE AGILE. The trial was designed with two phases: a 12-week, double-blind, placebo-controlled period, followed by a longer dose-blind period extending to 48 weeks. After this, patients who completed the first part of the trial were eligible for the open-label extension (OLE), where everyone received BKZ at a 160 mg dose every 4 weeks, continuing through week 256 (about five years).
Key Findings:
1. Efficacy Results:
• About 84% of the original participants entered the OLE, and roughly 79% completed the full five years.
• After the first 48 weeks, 51.7% of participants achieved a 40% improvement in AS symptoms (ASAS40), and 49.3% had a significant reduction in disease activity (ASDAS < 2.1). By week 256, these percentages remained similar, with 49.7% and 41.6% respectively.
• In terms of disease activity, patients saw a notable reduction from baseline to week 48 (ASDAS score dropped from 3.9 to 2.1) and these improvements were sustained through week 256. A similar trend was seen with reductions in pain and stiffness, measured by the BASDAI score, which dropped from 6.5 to 3.0 by week 48 and remained stable at 2.5 at the five-year mark.
• Improvements in physical function and quality of life were also significant. By week 256, participants showed ongoing betterment in the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Ankylosing Spondylitis Quality of Life (ASQoL) scores, with noticeable gains from baseline that persisted throughout the study period.
2. Safety Results:
• Over the five years, BKZ continued to show a good safety profile. The overall rate of adverse events was measured as 134.6 events per 100 patient-years, while serious adverse events occurred at a much lower rate of 5.2 per 100 patient-years.
• Candida infections (a type of fungal infection) were noted more frequently in the first 48 weeks of treatment, but the rate significantly dropped over the extended five-year period. Importantly, all these infections were mild to moderate, and only one case led to the patient stopping treatment. There were no reports of systemic fungal infections.
• Serious infections, injection site reactions, and other adverse events like uveitis and inflammatory bowel disease (IBD) remained rare throughout the five years, with rates of 1.4 per 100 patient-years for serious infections and 0.2 per 100 patient-years for injection site reactions.
Conclusion:
This five-year study of BKZ showed that the drug was not only effective in reducing the symptoms of ankylosing spondylitis but also maintained these improvements over the long term. Most patients saw sustained reductions in pain, stiffness, and overall disease activity. The safety profile was consistent with earlier findings, with no new or unexpected safety concerns emerging during long-term use.
In summary, BKZ offers a promising treatment option for patients with ankylosing spondylitis, delivering long-term relief from symptoms while maintaining a low risk of serious side effects. This study is significant as it provides the first long-term data (up to five years) for BKZ in treating AS, contributing to the understanding of its sustained safety and efficacy.