Dual IL-17A and IL-17F inhibitor provides complete skin clearance in psoriasis

Psoriasis

By Michael Woodhead

10 Feb 2021

The latest biologic for psoriasis – bimekizumab – provides more rapid and complete clearance of symptoms than current mAbs through a novel dual action inhibiting IL-17A and IL-17F, two studies suggest.

The drug has the potential to become the drug of choice for more resistant psoriasis, although there are still questions about its adverse effects such as oral candidiasis and inflammatory bowel disease, according to a commentary accompanying the trials published in the Lancet.

In one study, the BE-VIVID phase 3 trial, bimekizumab was found to be more effective than the IL-12/23 inhibitor ustekinumab and placebo for the treatment of moderate to severe plaque psoriasis in 567 adults.

At week 16,  90% improvement in the PASI score (PASI90) was achieved at week 16 by 85% of patients on bimekizumab, compared with 50% of those on ustekinumab and 5% of patients on placebo. An IGA response of 0 or 1 was achieved by 84% of patients on bimekizumab, compared with 53% on ustekinumab and 5% on placebo. Complete skin clearance (ie, PASI100 or an IGA score of 0) was seen at week 16 in 59% of patients on bimekizumab compared with 21–22% of patients treated with ustekinumab.

These benefits were maintained up to week 52, the study investigators reported. Rates of serious treatment-emergent adverse events were similar for bimekizumab and ustekinumab (6% vs 8%), but mild oral candidiasis was experienced by 15% of patients receiving bimekizumab over the year. There was one case of severe oral candidiasis that resolved and one new case of IBD in a patient receiving bimekizumab.

A second study – BE-READY – involving 435 patients who received bimekizumab or placebo showed 70% rates of complete skin clearance at week 16 with the biologic and sustained skin clearance after bimekizumab withdrawal (median time to loss of PASI75 was 32 weeks after the last dose).

The commentary by Dr William Huang and Dr Steven Feldman of Wake Forest School of Medicine said bimekizumab appeared to offer some improvement over current IL-17 and IL-23 inhibitors, which were are already giving more than 90% of patients a solid improvement in their psoriasis, as measured by a PASI75 score.

They said the more rapid and durable effects on psoriasis could be attributed to the dual Il-17A/IL-17F inhibition, since complete inhibition of these pathways had previously been shown to lead to a greater reduction in the production of pro-inflammatory cytokines, the expression of psoriasis-linked genes, and inflammatory cell migration, compared with inhibition of IL-17A alone.

“Bimekizumab might be our most effective biologic for psoriasis yet. It seems to be useful for patients with severe disease for whom other treatment options have not been successful and perhaps for patients who would prefer to choose the most effective, fastest acting, self-injected treatment,” they wrote.

However, the question of whether the drug should be offered as a first-line treatment for everyone with severe psoriasis would depend on balancing the benefits with risk of side effects,  they added.

While mild oral candidiasis may be controlled with an occasional fluconazole pill and IBD was seen in only one in 600 patients, the risk-benefit balance was subjective and would have to be considered after discussion with the patient, they said.

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