WASHINGTON – It was nearly as effective in patients refractory to anti–tumor necrosis factor (TNF) therapy as it was to those naive to the treatment.
The antibody, which is derived directly from healthy human volunteers and then lab expanded, also improved patients’ quality of life in a “clinically meaningful way,”said at the annual meeting of the American Academy of Dermatology.
“These are sick people, and improvement of this kind is really something very important,” said Dr. Gottlieb of Mount Sinai Medical Center in New York. “I think what we see here supports the movement of bermekimab into phase 3 studies for HS [hidradenitis suppurativa].”
Bermekimab is the first inhibitor of IL-1 alpha to be investigated in HS. An overabundance of the cytokine produces several potentially problematic effects. IL-1 alpha induces inflammatory cells to migrate into the skin, drives neoangiogenesis, potentiates pain, and induces matrix metalloproteinase. The last two are particularly an issue in patients with HS. The abscesses and fistulas cause severe pain, which Dr. Gottlieb said is an undertreated and an underappreciated driver of disease disability. The tissue breakdown characteristic of the disease can also be highly disfiguring. “Many patients, especially my female patients, look as if they are basically autodigesting.”
IL-1 alpha also induces procollagen type I and III and fibroblast proliferation, contributing to the scarring many patients experience.
“Ten years ago, I thought it would be a potential target for HS,” Dr, Gottlieb said, and the idea has finally come to fruition through studies by biopharmaceutical companyin Austin, Tex. Dr. Gottlieb designed the treatment protocol and was a principal investigator on the study.
A similarly positive 2018employed twice-weekly intravenous infusions; this study utilized a more-concentrated form of the antibody delivered subcutaneously from prefilled syringes.
The study comprised 42 patients, 24 of whom had failed a course of anti-TNF therapy and 18 of whom were anti-TNF naive. Each group received bermekimab 400 mg subcutaneous once a week for 12 weeks. The primary endpoint was change on the Hidradenitis Suppurativa Clinical Response Score; good response was deemed at least a 50% reduction in abscesses and inflammatory nodules, with no new abscesses or draining fistulas. Secondary endpoints included pain scores, patient quality of life, and the physicians global clinical assessment.
At baseline, subjects in the anti-TNF–refractory group had a worse clinical profile than the naive patients, with more abscesses and inflammatory nodules (mean, 14 vs. 6) and worse scores on the Physicians Global Assessment. But they reported similar pain on a 10-point scale (around 8) and negative quality of life (17/30). Both groups experienced anxiety and depression.
Eight patients dropped out before finishing the trial for a variety of reasons, including family and transportation issues and comorbid illness. Only one discontinued for a reaction to the study drug (injection site redness). These patients were included in the final analysis in a last observation carried forward.
About 10% of patients began to experience improvement as soon as 2 weeks after the first injection. By week 6, 40% of the refractory patients and 10% of the naive patents had experienced a lesion reduction of at least 50%. By the end of the study, however, about 62% of patients in each group achieved that goal.
By week 12, the mean improvement in the Physicians Global Assessment was about 23% in the refractory group and 53% in the naive group. Both results were significant improvements over baseline.
The mean improvement in the pain score was about 54% in the refractory group and 65% in the naive group. In a scale that measured patients’ view of their disease severity, refractory patients reported a mean 40% improvement, and naive patients, a mean 67% improvement.
There were 57 adverse events recorded; 94% were grade 1 or 2. There were two serious adverse events requiring hospitalization – a fall and an admission for HS pain. Neither were judged related to the study drug. Two patients experienced injection site reactions and one patient experienced six bouts of nausea. There were no serious infections, no major cardiovascular events, and no neoplasms.
Dr. Gottlieb designed the study protocol and was a principal investigator. She did not receive financial compensation from the company.