Matthew Zirwas, MD: How Do Emerging HS Treatments Line Up?

As previously discussed at dermatology conferences this year, hidradenitis suppurativa (HS) looks to be following in the recent footsteps of vitiligo and alopecia areata as a chronic skin disease with a series of investigative and established pathway-targeting agents in development to potentially become the first drug indicated by the US Food and Drug Administration (FDA) to treat the patient population.¹

Progressing drug classes like interleukin 17 (IL-17) and Janus kinase (JAK) inhibitors are nearing potential FDA decision with enough substantial clinical evidence that dermatologists are now wondering, “How will I treat my patients with HS one year from now?”

One expert shared an idea.

In the second segment of an interview with HCPLive during the Maui Derm 2023 NP + PA Summer Conference in Colorado Springs this week, Matthew Zirwas, MD, director of the clinical trials and dermatitis center at Dermatologists of Greater Columbus, discussed his current and future blueprint for managing HS.

Beginning with IL-17 inhibitors in development, Zirwas cited recent data stating a combination of biologic therapies with surgical intervention—however uncommon to dermatologists—is associated with “amazingly better outcomes” for patients.

“Really what that looks like—whether we’re talking about adalimumab…bimekizumab or (secukinumab)—you put them on the drug, you let their disease get calmed down, probably about 3 months in,” he explained. “And any residual fissure, fistulas, lesions, anything at that point, you can excise them or you can deroof them. You almost think of the medical therapy as neoadjuvant.”

From Zirwas’ perspective in and out his involvement with clinical research, he believes IL-17 inhibitors will provide slightly better benefit and safety than tumor necrosis factor (TNF) inhibitors—but will pale to the benefit of JAK inhibitors including upadacitinib and povorcitinib. Regarding povorcitinib, he cited recent phase 2, 52-week trial data showing ≥100% improvement per HS Clinical Response (HiSCR 100) in approximately one-quarter of treated patients.²

“That is crazy for a disease that has been so hard to treat,” Zirwas said. “I think the JAK inhibitors are going to be reliably effective, and deeply effective.”

With none of these prospective drugs having been granted FDA indication for HS yet, Zirwas emphasized the utility of more widely available treatments like oxybutynin. Per recent data, patients with HS initiated on standard antibiotic therapy then switched to oxybutynin experienced “dramatically prolonged” duration of their disease remission and reduction in HS flares.³

“Oxybutynin is a very safe, well-tolerated drug that I’ve been using for years for hyperhidrosis,” Zirwas said. “Apparently it works by having some effect on the follicular units or sweat glands…but it’s cheap, it’s easy, and it’s safe. So, until we get the really good drugs, that’s a good other option.”

When the currently barren field becomes hopefully laden with a litany of available, disease-altering therapies, Zirwas predicts the golden standard for clinically improved HS will be HiSCR 75—which drug will bring more patients to a significant rate of disease resolution?

“You’re not going to get rid of scars, you’re not going to get rid of fistulas, but you’re going to make the inflammatory lesions and fistulas stop being inflamed, painful and symptomatic,” he said. “I think it’s going to be a baseline (biologic) therapy, then they’ll have prescription for minocycline (for flare risk). That’s how I imagine I’ll be managing HS in the future.”

References

1. ^{Kunzmann K. Jennifer Hsiao, MD: IL-17 Inhibitors for Hidradenitis Suppurativa. HCPLive. Published June 11, 2023. https://www.hcplive.com/view/jennifer-hsiao-il-17-inhibitors-hidradenitis-suppurativa}
2. ^{Incyte Announces 52-Week Results From Phase 2 Study Evaluating Povorcitinib (INCB54707) In Patients With Hidradenitis Suppurativa. Press Release. Incyte. Published February 10, 2023. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-52-week-results-phase-2-study-evaluating}
3. ^{Molinelli E, D'Agostino GM, Sapigni C, et al. Oral oxybutynin chloride therapy in the management of hidradenitis suppurativa: A prospective study. J Eur Acad Dermatol Venereol. 2023;37(6):e744-e746. doi:10.1111/jdv.18901}