Topical roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, may be a promising treatment for people with mild hidradenitis suppurativa (HS), according to the results of a small prospective case series.

The case series described three patients with mild HS (Hurley stage I disease) treated off-label with once-daily topical roflumilast cream 0.3%, which is approved for plaque psoriasis in adults and children aged 6 years or older. At baseline, on day 30, and on day 60 following treatment initiation, the investigators assessed objective inflammatory lesion counts as well as patient-reported symptoms, including pain, itch, odor, and drainage.

Patients were receiving stable doses of biologic or antiandrogen therapy and had stopped taking medicated topical treatments or corticosteroids 4 weeks before and remained off those treatments during the study. Patients A and B (both 36-year-old women) had two nodules and abscesses at baseline and were treated with chlorhexidine wash every other day. Because of a greater nodule burden at baseline, Patient C (a 31-year-old woman) started treatment with spironolactone.

All three patients experienced a reduction in nodules by 30 days, with no formation of new lesions, and by 60 days, all had achieved complete clearance of nodules. Improvement in symptoms mirrored these findings, particularly with itch, which improved in all patients by 30 days, with continued relief through 60 days. Improvement was observed even in the patient with the highest baseline lesion count and symptom severity.

The treatment was well tolerated, with no reports of systemic or local adverse events, such as burning, stinging, or gastrointestinal symptoms. The report was published online on December 17 in JAAD Case Reports.

“The key takeaway is that topical roflumilast may represent a promising therapy and showed a consistent signal of benefit in this small cohort, with improvement in both inflammatory lesions and patient-reported symptoms within the first month and sustained benefit through 2 months,” senior author Adam Friedman, MD, professor and chair of dermatology, The George Washington University, Washington, DC, told Medscape Medical News.

‘Window of Opportunity’

Mild HS has traditionally been treated with antibiotics and intralesional corticosteroid injections. Short courses of systemic corticosteroids were used for flares. However, these approaches “raise concerns about antibiotic resistance and long-term effects of steroid use in sensitive areas,” Friedman said.

“We’re seeing more patients with HS earlier in their disease, which is fantastic, given that we often miss the window of opportunity to prevent permanent disfigurement,” he said. But despite “advocacy-driven research and a rich therapeutic pipeline” of agents under investigation, “there still remains a significant gap in targeted treatment options for mild disease.”

Newer topical anti-inflammatory agents approved for other conditions “have mechanisms that align well with what we understand about HS pathophysiology,” Friedman continued.

Mechanistically, roflumilast controls the amplitude and duration of the effects of cyclic adenosine monophosphate (cAMP), according to Friedman and co-authors. cAMP downregulates proinflammatory cytokines and PDE4 degrades cAMP to AMP, so its inhibition increases intracellular cAMP levels, downregulating pro-inflammatory cytokines involved in the HS pathophysiology.

“Given the biologic rationale for PDE4 inhibition and prior reports of benefit with oral roflumilast in more severe disease, we wanted to explore whether a topical formulation could offer a safer, more targeted option for patients with mild HS,” Friedman said.

The researchers were gratified to see that topical roflumilast was effective for mild HS in the case series. This type of targeted treatment can potentially “alter the [HS] disease trajectory,” Friedman said.

But although these findings are encouraging, they shouldn’t be “overinterpreted,” he cautioned. The case series was small and of short duration. Moreover, “mild HS can fluctuate and there was no control group, so larger, controlled studies are clearly needed.”

Useful Addition to the Treatment Toolbox

“In clinical practice, I view topical roflumilast as a reasonable, individualized off-label consideration for select patients with mild Hurley stage I disease — particularly those who are cycling through ‘old school’ approaches,” Friedman commented.

“If used, it should be with informed patient discussion, clear expectations, and structured follow-up to objectively assess benefit,” he added.

He cautioned that it is “not a replacement for foundational HS care, but it may represent a useful addition to our early disease treatment toolbox.”

Commenting on the study for Medscape Medical News, Martin Okun, MD, of the Department of Dermatology at Fort HealthCare in Fort Atkinson, Wisconsin, said he doesn’t think the information in this case report “suffices to start prescribing roflumilast off-label, except in very unusual circumstances — for example, if the patient cannot tolerate or has failed [other treatments] or has concerns about other treatments.” Although it doesn’t appear to have systemic toxicity concerns, “we don’t [have] very much local tolerability information in patients with this disease state,” he added.

It is possible that two of the patients improved because of natural fluctuations in disease severity unrelated to roflumilast use, he said. And the third patient was concomitantly taking spironolactone, so it’s unclear if the dramatic improvement may have been confounded by this medication use.

Nevertheless, the case series “generates an interesting hypothesis that should be tested with larger, longer controlled trials,” said Okun.

The study received no funding. Friedman reported being a speaker and consultant for Arcutis Biotherapeutics. Okun reported being a consultant for Bluefin Biomedicine.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).