Real‐world experience with upadacitinib in hidradenitis suppurativa: efficacy and safety in patients with dermatological comorbidities

Dear Editors, Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, and debilitating skin disorder of the hair follicles, with a multifactorial pathogenesis. It is characterized by painful, deep-seated lesions that most commonly affect the axillae, inframammary areas, groin, buttocks, and perineum.1 Managing moderate-to-severe HS remains a major clinical challenge and often involves a combination of systemic therapies and local wound management. To date, only two biologic agents – adalimumab (an anti-TNF-α monoclonal antibody) and secukinumab (an IL-17A inhibitor) – have been approved by the FDA and EMA for HS treatment.2-6 More recently, Janus kinase (JAK) inhibitors have emerged as promising alternatives. Oral JAK1 inhibitors have shown preliminary efficacy in phase II studies and cohort analyses and are currently under evaluation in phase III trials.7 Upadacitinib is a selective JAK1 inhibitor approved for the treatment of rheumatoid arthritis and atopic dermatitis in adults and adolescents (≥ 12 years). In this real-world case series, we assessed the efficacy and safety of upadacitinib in patients with moderate-to-severe HS who had failed conventional biologic therapies (TNF-α or IL-17 inhibitors). Seven patients with refractory HS were treated with upadacitinib in our department. Dosing regimens varied based on the patient's comorbidities and disease severity: two patients received 45 mg daily for three months followed by 30 mg daily; three received 30 mg daily from the outset; and two were treated with 15 mg daily. In five cases, the prescription was made for approved indications of the drug (ulcerative colitis, Crohn's disease, or atopic dermatitis), while in two patients an off-label request was submitted to the local territorial pharmacy. All patients received standard wound care and routine laboratory monitoring throughout treatment. Patients were assessed at baseline, three months, six months, and one year using the International Hidradenitis Suppurativa Severity Score System (IHS4), achievement of IHS4-55, abscess and nodule (AN) count, Visual Analog Scale (VAS) for pain, and Dermatology Life Quality Index (DLQI).8 No concomitant systemic treatments were allowed during the treatment period. All patients underwent routine laboratory monitoring as per clinical practice guidelines. The cohort comprised five females and two males, with a median age of 29 years (range 18–47) and median BMI of 27.4 kg/m2 (range 20.7–33.2). Five patients exhibited an inflammatory phenotype, and two had a follicular and mixed phenotype. Comorbid diseases included ulcerative colitis (n = 1), Crohn's disease (n = 1), psoriasis (n = 1), and atopic dermatitis (n = 3). The clinical and demographic features of the cohort is presented in Table 1. At baseline, the median IHS4 score was 14 (range 5–43); median AN count 3 (range 1–8); median VAS pain score 6 (range 3–9); and median DLQI score 13 (range 5–20). At three months, these values improved to IHS4 = 5 (range 1–36), AN = 2 (range 0–4), VAS = 3 (range 2–6), and DLQI = 9 (range2-14). At six months, further improvements were observed: IHS4 = 2 (range 0–18), AN = 1 (range 0–1), VAS = 2 (range 0–3), and DLQI = 4 (range 0–8) (Figure 1). After one year of treatment, the clinical improvement was maintained and even further enhanced in several patients. No adverse events were reported across the follow-up period. Treatment was well tolerated across all dosing regimens. All patients are currently still receiving upadacitinib, and no treatment discontinuations have occurred during follow-up (up to twelve months). These findings suggest that upadacitinib may represent a promising therapeutic option for patients with moderate-to-severe, treatment-refractory HS. Improvements were observed in both clinical parameters and patient-reported outcomes, including pain and quality of life, consistent with prior studies. The marked reduction in IHS4 scores and AN counts supports the hypothesis that JAK1 signalling is central to HS pathogenesis (Figure 2).9 Notably, the mean IHS4 score demonstrated a marked reduction from baseline to both the three-month and six-month timepoints, with most patients achieving near-complete resolution of AN count. These findings support the hypothesis that JAK1 signaling plays a central role in the inflammatory cascade of HS.10 Importantly, no adverse events – such as viral reactivation or liver enzyme elevations, which have been previously reported – were observed in our cohort. This may reflect the small sample size and short follow-up duration. Limitations include the small patient number, heterogeneity in dosing regimens, and the presence of inflammatory comorbidities, which may confound interpretation. Nevertheless, our real-world experience reinforces the potential of JAK1 inhibition as an effective strategy for HS patients unresponsive to biologics, with clinically meaningful improvements in disease activity and quality of life. None.