A phase 3 randomised controlled trial of the dual IL-17A and IL-17F inhibitor bimekizumab in patients with active psoriatic arthritis (PsA) has confirmed its efficacy, and safety out to 52 weeks, but questions remain about its advantage over IL-17A blockade alone.
The BE OPTIMAL study randomised 852 biologic-naive patients to either 160mg subcutaneous bimekizumab every four weeks, 40 mg adalimumab every two weeks or placebo. About 58% of patients were also on concomitant methotrexate.
Presenting the results at the late-breaking session of ACR Convergence, Professor Christopher Ritchlin said the primary endpoint of ACR50 at week 16 was attained by 43.9% of patients on bimekizumab, 45.7% of the reference group on adalimumab, and 10% of placebo-controlled controls.
At week 16, controls were switched to bimekizumab for the rest of the study. ACR50 at week 52 was 54.5% for those on bimekizumab for the full duration of the study, 50.0% for those on adalimumab and 53.5 % for those who switched from placebo to bimekizumab.
Attainment of PASI100 at 16 weeks favoured bimekizumab (47.5%) compared to adalimumab (20.6%) and placebo (2.1%). At 52 weeks, responses were 60.8% for bimekizumab, 48.5% for adalimumab and 65.0% for the initial controls switched to bemekizumab.
Professor Ritchlin, Director of the Clinical Immunology Research Unit at the University of Rochester, New York, said for ACR20, ACR50 and ACR70 there was a rapid rise in response as patients switched from placebo to bimekizumab.
Similarly with PASI75, PASI90 and PASI100, there was a rapid rise in response after patients made the switch.
Minimal disease activity (MDA) in each group was similar at 52 weeks (55%, 52.9% and 53.8% respectively).
As well, the study found no radiographic progression in the vast majority (~90%) of bimekizumab-treated patients.
The most frequently reported TEAEs during the study were nasopharyngitis, upper respiratory tract and urinary tract infections.
Oral candidiasis, seen in about 5% of bimekizumab treated patients, was higher than in adalimumab-treated patients. There were no cases of systemic candidiasis.
Professor Ritchlin said the study had shown long-term efficacy and tolerability of the dual IL-17A and IL-17F inhibitor.
“Bimekizumab-treated patients with PsA demonstrated efficacy across both joint and skin outcomes, which was sustained from week 16 to week 52,” he said.
However, as previously reported in the limbic in 2020, there was no evidence yet of its superiority over a IL-17A inhibitor.
“…whether or not combining an antibody that hits both of these [targets] is going to be more advantageous than just IL-17A, I think it’s possible but we don’t have that data yet.”
“Obviously the other concern is going to be ‘Are we going to have a high level of safety events compared to IL-17A?’ and in this study it didn’t seem to be the case.”
An extension trial BE VITAL is ongoing.
The study was funded by UCB Pharma.