With one approved biologic available and many more under investigation, the future of treatment for hidradenitis suppurativa (HS) looks very promising, according to Francisco Kerdel, MD, dermatologist with the Florida Academic Dermatology Center, Coral Gables, Fla.
“This is a disease that used to be thought of as an infectious process, now we know it's mainly an inflammatory one, and there's a whole host of drugs in the immunological era that may be applicable to this disease,” Dr. Kerdel said in an interview with Dermatology Times.
Many drugs effective in psoriasis and rheumatoid arthritis may also be effective in HS, said Dr. Kerdel, who provided an update on biologic treatment of this painful chronic autoinflammatory condition at the 2018 American Academy of Dermatology Annual Meeting in San Diego, Calif.
Adalimumab is the first and only U.S. Food and Drug Administration approved option for moderate to severe HS. When the drug is effective for patients, “it does change their lives,” Dr. Kerdel said; however, it is not a panacea, since not all cases will respond.
Despite the hope for additional biologic options, many investigations remain in their infancy and are primarily limited to case reports and phase 1 or 2 trials. Nevertheless, certain treatments including interleukin (IL)-1–directed therapies may hold promise, he added.
The approval of adalimumab was based in part on data from PIONEER I and PIONEER II, two multicenter, double-blind, placebo-controlled studies including a total of 633 patients with moderate to severe HS. The primary end point of the studies was week 12 assessment of clinical response, defined as a ≥50% reduction from baseline in abscesses and inflammatory nodule count, plus no increase in abscess or draining-fistula counts.
In PIONEER I, clinical response rates at week 12 were 41.8% for the adalimumab-treated patient group, compared to 26.0% for placebo (P = 0.003), and in PIONEER II, 58.9% for adalimumab versus 27.6% for placebo (P < 0.001), according to results published in the New England Journal of Medicine.
“For patients who have failed the traditional systemic antibiotic therapies that we use in HS, adalimumab becomes a very good choice,” said Dr. Kerdel.
Serious adverse events over 12 weeks of treatment occurred in 1.3% of adalimumab-treated patients and 1.3% of placebo-treated patients in PIONEER I, and in 1.8% and 3.7% of adalimumab- and placebo-treated patients, respectively, in PIONEER II, according to published results.
In clinical practice, adalimumab is “very well tolerated,” Dr. Kerdel said. We would have thought there would have been a high instance of infections, but we haven't found that to be the case.”
Other tumor necrosis factor-alpha inhibitors including etanercept and infliximab have been tried in HS. Phase II trials of etanercept have reported conflicting results, according to a recent report in the Journal of Dermatological Treatment, and the general consensus is that the treatment is “not effective” in moderate to severe HS, according to authors.
In contrast, infliximab improved HS Severity Index scores in a phase 2 randomized, double-blind, placebo-controlled study including 39 patients with moderate to severe HS, though no phase 3 studies are known to be planned or in progress, authors of that report added. In the phase 2 study, infliximab-treated patients also had significant improvements versus placebo in Dermatology Life Quality Index score and visual analog scale score, according to investigators.
Dr. Kerdel indicated that agents targeting IL-1 or IL-17 are among the treatments to watch as potentially promising agents for the treatment of HS. “They're also coming into the picture, so time will tell,” he said.
For example, the IL-1 receptor A antagonist anakinra significantly reduced disease activity score measures in one 20-patient randomized, placebo-controlled trial including 20 patients with Hurley stage II or III HS, according to the review in the Journal of Dermatological Treatment.
Likewise, the IL-17A inhibitor secukinumab has shown promise, the authors said. In a case report, the fully human monoclonal antibody was administered to a patient with Hurley Stage III HS that was resistant to multiple treatments, including adalimumab, infliximab, and anakinra. Following 12 weeks of treatment, the number of patient-reported lesions over the preceding 4 weeks dropped from 23 to 7, according to investigators.
An early phase 1 study of secukinumab in patients with moderate to severe HS is underway. The primary end point of the study, which is expected to be completed by January 2019, according to ClinicalTrials.gov, is the proportion of patients achieving Hidradenitis Suppurativa Clinical Response by week 24.
Dr. Kerdel advised dermatologists to stay tuned for more studies in HS: “there's going be a lot of new information when it comes down to the use of different biologics that act in different pathways in the inflammatory cascade,” he said.
"F114 - Biologic Therapy in Dermatology Beyond Psoriasis, Hidradenitis Suppurativa: Biologic Therapy," Francisco Kerdel, M.D., 5:30 p.m., Sunday, February 18. American Academy of Dermatology 2018 annual meeting, San Diego.