Bimekizumab, a monoclonal antibody that targets both interleukin (IL)-17A and IL-17F, showed promise as a treatment for ankylosing spondylitis (AS) in a phase IIb trial, investigators reported.
In a randomized dose-ranging study, a 40% improvement on the Assessment of SpondyloArthritis International Society (ASAS40) criteria at week 12 was seen in 46.7% of those receiving 160 mg subcutaneously every 4 weeks, according to Désirée van der Heijde, MD, of Leiden University Medical Center in the Netherlands, and colleagues.
With that dose, the odds ratio of achieving an ASAS40 response at week 12 compared with placebo was 5.5 (95% CI 2.3-13.5), the researchers reported online in .
The IL-17 pathway is a recognized target in AS, with efficacy having been demonstrated for (Taltz) and (Cosentyx), both of which are IL-17A antagonists.
In vitro studies have indicated that inhibiting both IL-17A and IL-17F, which together can increase inflammatory processes and are found in high levels of the serum of AS patients, might provide greater anti-inflammatory benefits than targeting IL-17A alone. Bimekizumab has previously shown efficacy in and .
Accordingly, van der Heijde and colleagues enrolled 303 adults with radiographically confirmed sacroiliitis, randomizing them to every-4-week regimens of 16 mg, 64 mg, 160 mg, 320 mg, or placebo for 12 weeks.
At the end of the 12-week double-blind phase, those initially given 16 mg, 64 mg, or placebo received 160 mg or 320 mg every 4 weeks through week 48, and those originally given 160 mg or 320 mg continued on those doses.
Participants' mean age was 42, and most were white men. The time since first symptoms was almost 15 years, and mean Ankylosing Spondylitis Disease Activity Score (ASDAS) was 3.9, representing "highly active, established AS," the investigators noted.
The primary efficacy endpoint of ASAS40 at week 12 was met by more patients in all bimekizumab groups compared with placebo: 29.5% on 16 mg, 42.6% of those on 64 mg, 46.7% of those on 160 mg, and 45.9% of those on 320 mg, versus 13.3% of those receiving placebo.
The responses were rapid, occurring by week 1 in 8.2% to 19.7% of the active treatment groups compared with 0% of the placebo group.
Changes on the ASDAS from baseline at week 12 were -0.9 in the 16 mg group, -1.7 in the 64 mg group, -1.4 in the 160 mg group, and -1.5 in the 320 mg group compared with -0.4 in the placebo group. Similarly, changes on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were -1.7, -2.7, -2.5, and -2.9, respectively, compared with -1 in the placebo group.
On multiple other endpoints at week 12, outcomes also favored bimekizumab. For instance, 50% improvements on the BASDAI were reported by 37.9% of patients in the 160 mg group and by 47.5% of those in the 320 mg group. Patient global assessment of disease activity, spinal pain, fatigue, and morning stiffness all improved in the active treatment groups, as did measures of patient quality of life.
Through week 48, ASAS40 response rates continued to rise, reaching 58.6% for those receiving 160 mg and 62.3% of those given 320 mg. Among patients who had originally been randomized to placebo, 54.2% of those re-randomized to 160 mg had achieved an ASAS40 response by week 48, as did 50% of those re-randomized to 320 mg.
Overall levels of inflammation, as reflected in measurements of C-reactive protein, fell quickly and were maintained through week 48.
Patient-reported outcomes also continued to improve through week 48, including patient global assessment of disease activity, morning stiffness, spinal pain, function, and quality of life.
During the double-blind 12-week phase, adverse events were reported by 37.9% of patients receiving the active treatment and by 43.3% of those given placebo. During the 48-week follow-up, the most common treatment-emergent adverse event was nasopharyngitis, reported by 11.2%.
Serious adverse events occurred in 1.2% of the bimekizumab-treated groups in the double-blind phase and by 4.3% during the 48-week follow-up. Mild-to-moderate oral candidiasis developed in 4.3% of patients in the 320 mg group during the double-blind period and in 5.3% of patients receiving bimekizumab overall.
There also were four cases of inflammatory bowel disease. Two of the cases were Crohn's disease, one of which was considered related to treatment, and two were ulcerative colitis, neither of which was thought to be treatment-related. The incidence of these events was similar to what has been reported with other biologics, van der Heijde and co-authors noted.
The findings of the trial suggest that bimekizumab may be "a promising therapeutic option" in AS, with improvements in multiple aspects of disease being rapid and sustained. "These results support phase III evaluation of bimekizumab in axial spondylitis [in and ] to determine the clinical benefits that may be associated with neutralizing IL-17F in addition to IL-17A," the researchers concluded.
A limitation of the study, they said, was the relatively brief (12-week) placebo-controlled phase.
Disclosures
The study was funded by UCB Pharma.
The authors reported financial relationships with multiple companies, including UCB, AbbVie, Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Roche, Celgene, Merck Sharp & Dohme, Chugai, Altoona Centernical Research, Horizon, Merck, Genzyme, Sanofi, SUN Pharma, and Gilead; several authors were employees of UCB.
Primary Source
Annals of the Rheumatic Diseases
van der Heijde D, et al "Dual neutralization of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomized, double-blind, placebo-controlled, dose-ranging study" Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-216980.