A monoclonal antibody that neutralises IL-17A and IL-17F has reduced ankylosing spondylitis symptoms and was relatively well tolerated, a phase IIb trial finds
Bimekizumab, a monoclonal antibody that neutralises IL-17A and IL-17F, may be an effective and safe treatment for ankylosing spondylitis, a new phase IIb trial suggests.
The drug has demonstrated benefit for psoriasis and psoriatic arthritis, prompting Professor Désirée van der Heijde, of Leiden University Medical Center in the Netherlands, and colleagues to explore its use in this IL-17A mediated disease.
Other IL-17A antagonists, such as ixekizumab and secukinumab, have already been shown to help those with ankylosing spondylitis. However, in vitro studies suggest that inhibiting both IL-17A and IL-17F cytokines could be better at fighting inflammation than IL-17A drugs alone.
To test this, Professor van der Heijde randomly assigned 303 adults with radiographically confirmed sacroiliitis to receive a subcutaneous dose of either 16mg, 64mg, 160mg or 320mg of bimekizumab or a placebo every four weeks, for 12 weeks. At the end of this period, those initially receiving 16mg, 64mg or the placebo then began taking 160mg or 320mg every four weeks, while those originally given 160mg or 320mg continued the same treatment, until week 48.
The researchers were looking to see whether the participants would experience a 40% improvement on the Assessment of SpondyloArthritis International Society (ASAS40) criteria.
Patients taking bimekizumab were more likely to meet this threshold than those taking the placebo.
Specifically, half of the group receiving 160mg met the criteria by week 12, compared to 43% of the group taking 64mg and 30% of the group taking 16mg.
Only 13% of the placebo group met the criteria.
Patients were quick to respond to the drugs, with between 10 and 20% of patients in the active group benefitting within the first week.
Patients taking the drug also reported secondary benefits, including quality of life, patient global assessment of disease activity, spinal pain, fatigue and morning stiffness.
Many also improved by 50% or more on the BASDAI. More than one in three on the 160mg dose and almost half on the 320mg dose reached that threshold.
Overall inflammation, as measured by CRP levels, quickly fell and remained low until the study’s conclusion at 48 weeks.
The safety profile was comparable with others in the IL-17A inhibitor class. Adverse events were reported in 43% of the placebo group and 38% of the bimekizumab group.
By the end of the 48 weeks, serious adverse events were reported in 4% of the bimekizumab group.
Almost 5% of those taking the highest dosage reported mild to moderate oral candida, which were successfully treated with antifungals.
Four people reported inflammatory bowel disease over the course of the study. Two of these were cases of mild to moderate Crohn’s disease, and one was attributed to treatment. The other two cases of ulcerative colitis were considered unrelated to the treatment.
“Overall, bimekizumab was generally well tolerated across the treatment groups,” wrote Professor van der Heijde. “The safety profile in patients with active AS was as expected given previous studies of bimekizumab in patients with psoriasis or PsA.”
The findings suggest bimekizumab could be “a promising therapeutic option” for patients with ankylosing spondylitis, she added.
“Bimekizumab treatment resulted in rapid and sustained improvements across multiple outcomes of disease activity, quality of life and function,” she added, saying the findings supported the phase III trials underway.
Annals of the Rheumatic Diseases 2020, April 6
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