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The monoclonal antibody bimekizumab was more effective than ustekinumab (Stelara) or placebo for moderate-to-severe plaque psoriasis in a phase III trial, investigators reported.

At week 16, a 90% improvement on the Psoriasis Area and Severity Index (PASI90) was observed in 85% of patients randomized to bimekizumab compared with 50% of those given ustekinumab, for a risk difference of 35 (95% CI 27-43, P<0.0001), according to Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

The PASI90 response rate at week 16 was also compared with 5% of patients receiving placebo, for a risk difference of 80 (95% CI 74-86, P<0.0001), the researchers reported in their study online in .

"Ustekinumab has been one of the most effective treatments we've had," Lebwohl told 番茄社区app. "And the results at week 16 with bimekizumab were dramatically more effective than a treatment that is truly an excellent treatment."

Despite the increasing variety of effective psoriasis medications, there remains a subset of patients who do not have prompt and persistent skin clearance. "Consequently, an unmet need remains for a treatment that results in complete skin clearance with a reliably quick response," the investigators wrote.

Trial Overview

Inhibition of interleukin (IL)-17A with monoclonal antibodies such as secukinumab (Cosentyx) and ixekizumab (Taltz) has been shown to significantly improve psoriasis.

Bimekizumab selectively inhibits both interleukin (IL)-17A and IL-17F, both of which are overexpressed in the skin of patients with psoriasis, and inhibition of both in vitro has shown greater effects than inhibition of IL-17A alone in pathogenic processes such as blocking of pro-inflammatory cytokines and upregulation of psoriasis-related genes.

The researchers explained that since phase II studies have shown promise for dual inhibition of IL-17A and IL-17F, the team undertook a phase III trial at 105 sites in 11 countries, which was funded by UCB Pharma. The first 16 weeks were placebo- and active comparator-controlled, followed by a 36-week active comparator-controlled maintenance period.

The treatments consisted of bimekizumab, 320 mg every 4 weeks; ustekinumab, 45 or 90 mg every 12 weeks based on body weight; or placebo every 4 weeks. After week 16, patients initially in the placebo group were given bimekizumab, 320 mg every 4 weeks.

From December 2017 to December 2019, the investigators enrolled 567 adults with moderate-to-severe plaque psoriasis. Mean age of the participants was 46, three-quarters were men, and most were white; mean disease duration was 17 years.

Almost 40% of the patients had previously received biologic therapy, and 82% had been given some type of systemic therapy.

Efficacy

At week 16, a total of 84% of patients receiving bimekizumab had an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear), compared with 53% of those given ustekinumab (risk difference 30, 95% CI 22-39, P<0.0001) and 5% of those receiving placebo (risk difference 79, 95% CI 73-85, P<0.0001).

Also at week 16, complete skin clearance on the PASI100 was achieved by 59% of the bimekizumab group, 21% of the ustekinumab group (P<0.0001), and none of the placebo group.

On the Dermatology Life Quality Index, 67% of patients in the bimekizumab group reported scores of 0 or 1 at week 16 compared with 42% of those in the ustekinumab group and 12% of those in the placebo group (P<0.0001 for both).

Responses also were more rapid with bimekizumab. At week 4, after a single dose, PASI75 scores were observed in 77% of patients in the bimekizumab group compared with 15% of the ustekinumab group (OR 18.2, 95% CI 11-30.1, P<0.0001). "That response is faster than any of the other treatments we're used to," said Lebwohl.

The researchers explained that although direct comparisons cannot be made between clinical trials due to differences in trial design, the results suggest that bimekizumab might have a faster onset of treatment response than that reported with current IL-17A inhibitors such as ixekizumab and secukinumab based on published results.

"This is of relevance because speed of treatment response has been found to be of high importance to patients and remains an unmet need," Lebwohl and colleagues wrote.

In addition, responses persisted through week 52, with PASI90 scores in the bimekizumab and ustekinumab groups of 82% and 56%, respectively (OR 3.8, 95% CI 2.4-5.9, P<0.0001).

Safety

During the first 16 weeks of the study, serious adverse events occurred in 2% of patients receiving bimekizumab, 3% of those treated with ustekinumab, and 2% of those on placebo, the researchers reported. Four deaths occurred, none of which were considered treatment-related.

The most frequent adverse events throughout the 52 weeks of the study in the bimekizumab group were nasopharyngitis, oral candidiasis, and upper respiratory tract infections. Among the 15% of patients given bimekizumab who had oral candidiasis during the entire study, only one case was severe.

Oral candidiasis, or thrush, also has been observed with other IL-17 inhibitors, Lebwohl noted. "There are people who are born deficient in IL-17 who get a condition known as chronic mucocutaneous candidiasis and have very bad yeast infections, and if you knock out IL-17 in mice they get yeast infections. So in some ways it's comforting that the side effect we're seeing is the one we expect based on nature."

The oral candidiasis is almost always mild-to-moderate and is easy to treat, he added.

In an , William W. Huang, MD, and Steven R. Feldman, MD, of Wake Forest School of Medicine in Winston-Salem, North Carolina noted that the percentage of 15% of patients who developed oral candidiasis is higher than the 1-2% that has been observed among patients treated with other IL-17 inhibitors.

However, that 1-2% figure "is so low that even a 10-fold increased risk might not be particularly clinically meaningful, especially if the candidiasis is limited to mild to moderate oral involvement that is amenable to an occasional fluconazole pill," the editorialists wrote.

However, they continued, it's not yet known whether more serious fungal infections, such as esophageal or systemic, may develop over time. "Whether bimekizumab is the go-to drug for psoriasis or simply another option for patients with resistant disease will depend on how patients, in discussion with their clinicians, perceive the side effect profile," Huang and Feldman said.

The researchers said the study findings, with rapid, clinically meaningful, and durable responses, provide "strong evidence that bimekizumab could offer an additional treatment option for patients with moderate to severe psoriasis."

The study was limited in its duration and diversity of patients, the team noted.

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