番茄社区

Simultaneous inhibition of interleukin(IL)-17A and 17F with bimekizumab led to more rapid clearance of plaque psoriasis in significantly more patients as compared with the IL-17A inhibitor secukinumab (Cosentyx), a large randomized trial showed.

After 16 weeks, 61.7% of patients treated with bimekizumab had a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) compared with 48.9% of the secukinumab arm. The 12.7% absolute difference met statistical criteria for noninferiority and superiority in favor of bimekizumab. Clearance occurred more rapidly with bimekizumab, as 71.0% of patients randomized to the IL-17A/F inhibitor had 75% or greater reduction from baseline in the PASI score at 4 weeks compared with 47.3% of the secukinumab arm.

The principal difference in safety profiles was oral candidiasis, which occurred in 19.3% of the bimekizumab-treated patients versus 3.0% of the secukinumab patients, reported Kristian Reich, MD, PhD, of University Medical Center Hamburg-Eppendorf in Germany, during the American Academy of Dermatology (AAD) virtual meeting.

The study was published simultaneously in the .

"What this study is telling me is that if you want to get the optimal inhibition of the IL-17 pathway in psoriasis, you seem to need to block 17A and F, as bimekizumab is doing," Reich said of the results. "[Bimekizumab] was significantly superior when we look at the high response levels, PASI 100, compared to secukinumab. It was also a lot faster, obviously pointing to a relevant role of IL-17F in the pathophysiology of psoriasis."

"The safety price, if you will, is that you have somewhat more oral Candida, with the majority of cases with bimekizumab being mild to moderate," he added.

One Versus Two Isoforms

The IL-17A and 17F isoforms are in the pathophysiology of psoriasis and are overexpressed in psoriatic tissue. IL-17A is the more potent cytokine, but may exhibit higher expression in psoriatic skin lesions. Some evidence suggests that simultaneous inhibition of IL-17A and 17F might result in of inflammation and better clinical outcomes in psoriasis as compared with blocking just IL-17A.

Reich reported findings from the phase III trial comparing bimekizumab and secukinumab. In separate phase III trials, bimekizumab led to greater clinical improvement in moderate-to-severe plaque psoriasis compared with , (Stelara), and (Humira).

Eligible patients had moderate-to-severe plaque psoriasis (PASI score ≥12) for at least 6 months, involvement of ≥10% of body surface, and an Investigator's Global Assessment (IGA) score ≥3. Exclusion criteria included prior exposure to either study drug, no response to other IL-17 blockers, and no response to more than one biologic agent in any other class.

Patients were randomized 1:1 to bimekizumab once every 4 weeks (q4w) or secukinumab once weekly for 4 weeks then q4w thereafter. After 16 weeks, patients assigned to bimekizumab were re-randomized 1:2 to maintenance therapy q4w or q8w to week 48, and patients in the secukinumab arm continued q4w treatment.

The primary endpoint was the proportion of patients achieving PASI 100 at 16 weeks, comparing bimekizumab versus secukinumab first for noninferiority and then superiority. Secondary endpoints included PASI 75 at 4 weeks, PASI 100 at 48 weeks, and PASI 90 response and IGA response (0-1, at least two-step improvement) at week 16.

Data analysis comprised 743 randomized patients; 96%-97% of patients in both groups remained in the study through week 16, and 92% of the bimekizumab patients and 88% of the secukinumab patients remained on treatment to week 48.

Key Findings

The between-group difference in PASI 100 rates at 16 weeks met the statistical requirement for both noninferiority and superiority (P<0.001). At 48 weeks, PASI 100 rates were 67.0% for bimekizumab and 46.2% for secukinumab, which met criteria for noninferiority and superiority (P<0.001). During the maintenance phase, patients randomized to continue bimekizumab q4w or switch to q8w dosing exhibited significantly more improvement compared with the secukinumab arm (P<0.001), suggesting that the two dosing schedules are equally effective, said Reich.

The difference in PASI 75 at 4 weeks achieved statistical significance (P<0.001) in favor of bimekizumab and remained numerically better out to week 48. The proportion of patients who had PASI 90 and IGA responses at 16 weeks were 85.5% for both outcomes with bimekizumab and 74.3% and 78.6% with secukinumab.

"There are very clear messages from this study, when it comes to efficacy and speed of onset," said Reich. "The PASI 75 at week 4, which for bimekizumab means only one injection -- quite a significant difference of more than 20%. There's also a significant difference for PASI 90, so bimekizumab works faster than secukinumab."

Through 48 weeks, serious adverse events (AEs) occurred in similar proportions of patients treated with bimekizumab (5.9%) or secukinumab (5.7%). Rates of discontinuation because of AEs were 3.5% and 2.7%, respectively. Beyond oral candidiasis, AEs occurring in ≥5% of patients in any group included upper respiratory tract infection and urinary tract infection.

The chair of an AAD session on hot topics in dermatology and biologics said the bimekizumab data will be one of the major stories of the meeting.

"If you look at all of the pivotal trials in psoriasis, there's no phase III trial where at the end of the placebo control period, more than 50% of the patients achieve PASI 100," co-author Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai in New York City, told 番茄社区. "This drug is really effective. It's also very fast and it gives durable remissions."

Comment