‘Surprising and good’: Bimekizumab shows strong 5-year efficacy in ankylosing spondylitis
Key takeaways:
- There were no new safety signals, while all fungal infections were mild-to-moderate and non-systemic.
- Efficacy was persistent even with non-responder imputation.
A 5-year study of bimekizumab in ankylosing spondylitis encountered no new safety signals, with efficacy sustained even in a conservative analysis with non-responder imputation, according to data published in RMD Open.
“Bimekizumab is a new molecule that blocks IL-17A and IL-17F, so it blocks two cytokines,” Atul Deodhar, MD, MRCP, FACR, FACP, professor of medicine at Oregon Health & Science University, told Healio. “When such a new molecule is being tested, the first thing people want to know is, how safe is this?”
Previously, a phase 2b study (BE AGILE) found that bimekizumab (Bimzelx, UCB) led to “rapid and significant” improvements in ankylosing spondylitis disease activity at week 12, maintained to week 48. From there, patients who completed the trial could enter a 5-year open-label extension.
Their initial inclusion was based on fulfilling criteria for “ankylosing spondylitis,” not radiographic axial spondyloarthritis, a largely synonymous term that is now preferred.
All patients entering the open-label extension were switched to the same dosage: 160 mg every 4 weeks.
From baseline to week 256, BE AGILE comprised 1,231 person-years of exposure to bimekizumab. Overall, 95.4% of patients (n = 289) had at least one treatment-emergent adverse event, with the most frequent being nasopharyngitis (21.8%), upper respiratory tract infection (14.5%) and bronchitis (13.2%).
The study had positive results for fungal infections, one of the main safety concerns with bimekizumab, according to Deodhar.
“IL-17 is a cytokine that is important for controlling fungal infections, especially Candida,” he said. “Here, we are blocking IL-17A and IL-17F. There was a question how much candidiasis infection people will get and whether there will be a systemic candidiasis — that is terrible. And that never happened.”
Every fungal infection recorded in the study was non-systemic and mild-to-moderate in severity. The exposure-adjusted incidence rate (EAIR) for overall fungal infection was 7.4 per 100 patient-years, with Candida infections — mostly oral candidiasis — affecting 30 patients (EAIR: 2.6).
There were also good findings for other side effects of special interest — active inflammatory bowel disease (EAIR: 0.8) and anterior uveitis (EAIR: 0.7).
“If you take patients with ankylosing spondylitis, their lifetime risk is 40% of getting anterior uveitis,” Deodhar said. “Here, the risk of uveitis was very, very low. That was a surprise. That’s a good thing.”
According to the researchers, the efficacy initially observed at week 48 stayed consistent through 5 years. With non-responder imputation, 49.7% achieved Assessment of SpondyloArthritis International Society 40% response, while 41.6% met criteria for Axial Spondyloarthritis Disease Activity Score low disease activity.
Deodhar described the efficacy results as “quite surprising and good,” given the conservative approach of non-responder imputation.
“If for any reason a patient comes out of the study, even if they're doing well, they're considered a ‘non-responder,’” Deodhar said. “So, non-responder imputation is the strictest way of looking at efficacy.”
For more information:
Atul Deodhar, MD, MRCP, FACR, FACP, can be reached at deodhara@ohsu.edu.
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