Psoriasis

Next generation dual IL17 inhibitor shows promise against psoriasis


Dual neutralisation of interleukin IL17s appears to be more effective than current IL17A inhibitors against psoriatic arthritis but further work including direct comparison is needed.

While the current two IL17A inhibitors secukinumab and ixekizumab have shown good results in psoriatic arthritis, treatment with bimekizumab targeting both IL17A and IL17F appears to be associated with clinically meaningful improvements in both musculoskeletal and skin outcomes, according to a phase 2b randomised controlled trial of the novel agent.

The study, published in The Lancet, randomised 206 patients to dose finding groups of 16 mg, 160 mg (alone or with a 320 mg loading dose), and 320 mg bimekizumab or placebo.

The study found a 50% improvement from baseline in the American College of Rheumatology response criteria (ACR50) at 12 weeks in 27%, 41%, 46%, 24% and 7% of the groups respectively.

Patients in the 16 mg and placebo groups were then re-randomly assigned to either 160mg or 320 mg of the monoclonal antibody.

“By week 24, 37–60% of patients who remained on the same dose of bimekizumab from baseline had minimal disease activity, and these proportions were maintained at week 48,” the study said.

In patients in the 160 mg, 160 mg (loading dose), and 320 mg bimekizumab groups, PASI75 and PASI90 responses were also improved at week 24 and maintained at week 48.

The study noted the skin clearance responses were consistent with outcomes in previous clinical trials of bimekizumab in patients with moderate-severe psoriasis.

All doses of bimekizumab were associated with clinically significant improvements in HAQ-DI scores and the physical component of the Short-Form 36-item Health Survey, compared with placebo.

Treatment-emergent adverse events (TEAEs) were common (41% of bimekizumab treated patients v 57% of controls) but mostly of mild to moderate severity. They included nasopharyngitis and upper respiratory tract infections.

Occasional serious TEAEs included one case of atrial fibrillation in the placebo group, one case of drug-induced liver injury in the 160 mg bimekizumab group and one case of cellulitis in the 160 mg bimekizumab with loading dose group.

The study said the findings support the conduct of phase 3 trials.

“In this phase 2b study, dual neutralisation of IL17A and IL17F with bimekizumab treatment significantly improved the signs and symptoms of psoriatic arthritis at 12 weeks compared with placebo,” it said.

In an accompanying Comment article, Australian rheumatologist Professor Peter Nash said that before IL17 inhibitors were introduced, around 60% of patients achieving a 75% reduction in PASI scores was the best outcome that could be expected.

In the current study, the number needed to treat to achieve minimal disease activity was 1–2 and there were substantial responses in enthesitis measures and in patient-reported outcomes such as physical function and quality of life.

In addition “…no new IL17 inhibitor safety signals were reported, and the number needed to harm per serious adverse event was 22,” he said.

“Despite this being a trial with a failed primary endpoint and no active comparator group, responses in [this] trial were numerically better than what one would expect to see with commercially available IL17A inhibitors,” he wrote.

But the superiority of dual inhibition of IL17A and IL17F over inhibition of IL17A alone remains to be confirmed, he added.

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