Repurposed Anti-Inflammatory Pills Show Modest Promise Against Debilitating Skin Disease

Hidradenitis suppurativa is one of dermatology’s most punishing diseases, a chronic inflammatory condition that strikes the armpits, groin, and other skin folds where apocrine glands are dense. Patients endure recurrent, deeply painful nodules, abscesses, and draining tunnels beneath the skin that can persist for decades. Beyond the physical burden, the disease carries a heavy psychosocial toll, with studies linking it to elevated rates of depression and anxiety that worsen as severity climbs. Yet the therapeutic arsenal remains thin: only a handful of biologic drugs, including adalimumab and secukinumab, are formally approved, and many patients fail to respond adequately or lose response over time. That unmet need has pushed researchers to look for new uses for older, well-characterized drug classes, and a new systematic review now offers the most comprehensive picture yet of one such candidate: the phosphodiesterase-4 inhibitors.

A team led by Seyed Mohammad Vahabi and Elnaz Pourgholi, working with colleagues at Rush University Medical Center in Chicago and Tehran University of Medical Sciences, systematically combed through four major biomedical databases—PubMed/Medline, Scopus, Web of Science, and Embase—to gather every study in which patients with hidradenitis suppurativa received at least one phosphodiesterase-4 inhibitor. The review, published in Archives of Dermatological Research, was registered in advance on the PROSPERO registry, a step that helps guard against selective reporting. Two authors independently assessed the methodological quality of each included article using the National Heart, Lung, and Blood Institute’s quality assessment tools, a framework designed to grade the reliability of case series, case reports, and uncontrolled studies that dominate this corner of the literature.

The headline finding is a response rate that is encouraging but far from transformative. Across the pooled studies, 53.4 percent of patients who received at least one phosphodiesterase-4 inhibitor achieved HiSCR, the Hidradenitis Suppurativa Clinical Response. That endpoint, originally developed from a phase 2 adalimumab trial, is defined as at least a 50 percent reduction in abscess and inflammatory nodule count with no increase in abscesses or draining fistulas. It has become the standard yardstick for measuring treatment success in the field, which makes the new figure directly comparable to results reported for biologics in phase 3 trials. A majority of patients responding is meaningful, particularly given that many of the individuals in these studies had exhausted other options.

Safety data from the review paint a broadly reassuring picture. The most common adverse effects were gastrointestinal symptoms, weight loss, and headache, experienced by 20.9 percent of patients across all phosphodiesterase-4 inhibitors studied. These are familiar complaints for clinicians who prescribe this drug class in other inflammatory diseases, and they are generally manageable with dose titration and counseling rather than requiring discontinuation. The authors conclude that phosphodiesterase-4 inhibitors may offer a well-tolerated option for hidradenitis suppurativa with modest clinical response rates, positioning them as a potential addition to the treatment ladder rather than a replacement for the biologics that anchor moderate-to-severe care.

To understand why these drugs might work at all, it helps to look at the biology. Phosphodiesterase-4 is an enzyme that degrades cyclic adenosine monophosphate, a key intracellular messenger that dampens inflammatory signaling. When the enzyme is inhibited, cyclic AMP levels rise inside immune cells, suppressing the production of tumor necrosis factor-alpha and other inflammatory mediators that drive the lesions of hidradenitis suppurativa. This mechanism is the same one that made apremilast an approved oral therapy for plaque psoriasis, where the ESTEEM 1 phase 3 trial demonstrated its efficacy, and it explains why dermatologists began trying the drug off-label in patients whose hidradenitis overlapped with psoriatic disease.

The evidence base assembled in the review is a patchwork of study designs, reflecting how organically this off-label use developed. Apremilast, the most widely used inhibitor in the dataset, has been tested in a prospective open-label phase 2 study of mild-to-moderate disease, a randomized controlled trial for moderate hidradenitis suppurativa conducted by Dutch researchers, and multiple case series including one of nine patients with moderate-to-severe disease. Long-term follow-up data exist as well: a two-year study of initial responders to apremilast documented sustained treatment in patients who benefited early, an important signal that responses, when they occur, can be durable.

Newer molecules are also entering the picture. Orismilast, a next-generation inhibitor designed for higher potency, was evaluated in the OSIRIS trial, a phase 2a open-label dose-finding study that reported week 16 results in patients with mild to severe disease. Roflumilast, long approved for chronic obstructive pulmonary disease, has been reported to produce considerable improvement in individual patients and was assessed in a cohort study examining its effectiveness, safety, and drug survival in hidradenitis suppurativa. The inclusion of these newer agents matters because their pharmacological profiles may allow stronger enzyme inhibition with fewer gastrointestinal side effects, potentially improving on the tolerability ceiling that has limited older drugs.

The review also captures the creative combination strategies that clinicians have deployed when monotherapy falls short. Case reports describe apremilast paired with adalimumab to rescue patients who had a secondary failure of the biologic, and the combination of guselkumab with apremilast successfully treated a patient with both hidradenitis suppurativa and Crohn’s disease. Other reports document apremilast use in multimorbid patients with psoriasis and psoriatic arthritis, illustrating a practical advantage of small-molecule oral drugs: they can address multiple inflammatory conditions simultaneously in patients whose diseases overlap, something injectable biologics targeting a single cytokine cannot always do.

Context matters when weighing the 53.4 percent response figure. The approved biologics for hidradenitis suppurativa achieved HiSCR rates in the range of roughly half of treated patients in their pivotal phase 3 trials, but those results come from placebo-controlled studies where spontaneous improvement could be subtracted out. Most of the studies in the new review are open-label series without control groups, which inflates apparent efficacy because of regression to the mean and expectation effects. The authors are explicit about this limitation, calling for further high-quality randomized controlled trials to confirm efficacy, define optimal dosing strategies, and establish where these drugs belong in clinical practice. Until such trials are done, the true effect size remains uncertain.

Still, the review arrives at a moment when the treatment landscape for hidradenitis suppurativa is expanding rapidly, with biologics, Janus kinase inhibitors such as upadacitinib and INCB054707, and other targeted therapies all under active investigation. In that crowded pipeline, phosphodiesterase-4 inhibitors occupy a distinctive niche: they are oral, relatively inexpensive compared with biologics, backed by decades of safety experience in psoriasis and lung disease, and suitable for patients with milder disease or overlapping inflammatory conditions who might not qualify for biologic therapy. For the millions of patients living with this debilitating disease, the message from the new synthesis is cautiously hopeful—another tool may be joining the kit, provided that the rigorous trials the authors demand can confirm what the early data suggest.

Subject of Research: Efficacy and safety of phosphodiesterase-4 inhibitors for treating hidradenitis suppurativa

Article Title: Phosphodiesterase-4 inhibitors in the treatment of hidradenitis suppurativa: a systematic review

Article References: Vahabi, S. M., Pourgholi, E., Lasalle, C., Gainer, H., Wang, Y., & Amber, K. T. (2026). Phosphodiesterase-4 inhibitors in the treatment of hidradenitis suppurativa: a systematic review. Archives of Dermatological Research, 318(1), Article 434. https://doi.org/10.1007/s00403-026-04889-w

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04889-w

Keywords: hidradenitis suppurativa, phosphodiesterase-4 inhibitors, apremilast, roflumilast, orismilast, HiSCR, systematic review, dermatology, chronic inflammation, clinical trials, drug safety, biologics