Patient Population
Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).
In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.
The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
Adverse Events
Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.
Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.
One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.
There were no cases of uveitis, suicidal ideation, or deaths reported.
Comments on the Study
During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.
Dr. Walter P. Maksymowych
“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.
Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze.
Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.
“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.
Dr. Laura C. Coates
More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.
Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”
The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
A version of this article appeared on Medscape.com.