A 24-Week Real-World Study of Upadacitinib in Moderate-to-Severe Hidradenitis Suppurativa

Overview

Hidradenitis suppurativa is a chronic, recurrent inflammatory skin disease characterized by painful inflammatory nodules, abscesses, draining tunnels, and scarring. Patients with moderate-to-severe disease may experience inadequate responses, intolerance, or loss of response to conventional systemic therapies and biologic agents. This prospective, open-label, single-arm, real-world study will evaluate the effectiveness, safety, patient-reported outcomes, and treatment persistence of upadacitinib in 50 adults with moderate-to-severe hidradenitis suppurativa over 24 weeks. Participants will receive oral upadacitinib in routine clinical practice. A starting dose of 15 mg once daily is recommended. The dose may be increased to 30 mg once daily based on disease severity, treatment response, safety findings, drug accessibility, and shared decision-making between the investigator and the participant. Effectiveness assessments will include the Hidradenitis Suppurativa Clinical Response, abscess and inflammatory nodule count, International Hidradenitis Suppurativa Severity Score System, pain and pruritus numerical rating scales, Dermatology Life Quality Index, disease flares, rescue treatments, and surgical interventions. Safety assessments will include adverse events, serious adverse events, laboratory abnormalities, infections, thromboembolic events, major adverse cardiovascular events, hepatic abnormalities, lipid abnormalities, and cytopenias.

Hidradenitis suppurativa is a chronic, recurrent, inflammatory, and scarring skin disease that substantially affects pain, sleep, psychological well-being, social functioning, and quality of life. Although systemic antibiotics, retinoids, immunomodulatory agents, biologic therapies, and surgery are available, patients with moderate-to-severe or refractory disease frequently experience inadequate disease control, recurrent flares, persistent draining tunnels, treatment interruption, or failure of multiple treatment lines. The Janus kinase-signal transducer and activator of transcription pathway is involved in the signaling of multiple inflammatory cytokines implicated in hidradenitis suppurativa. Upadacitinib is a selective Janus kinase 1 inhibitor. Preliminary randomized clinical trial and real-world evidence suggests that upadacitinib may improve inflammatory lesion counts, hidradenitis suppurativa clinical response, disease severity, pain, and quality of life. However, upadacitinib remains an investigational and off-label treatment for hidradenitis suppurativa, and additional real-world data are required to characterize its effectiveness, optimal dosing, treatment persistence, and safety. This is a single-center, prospective, open-label, exploratory, single-arm investigator-initiated study conducted in a routine clinical care setting. Approximately 50 adults with moderate-to-severe hidradenitis suppurativa will be enrolled and followed for 24 weeks. A starting regimen of upadacitinib 15 mg orally once daily is recommended. For participants with severe disease, a high baseline inflammatory burden, or an inadequate clinical response, the dose may be increased to 30 mg once daily when considered clinically appropriate and acceptable from a safety perspective. Dose selection and adjustment will be based on the investigator's clinical judgment, participant preference, drug accessibility, prior treatment, comorbidities, and safety assessment. All dose changes, interruptions, discontinuations, concomitant treatments, rescue treatments, and surgical procedures will be documented. Study assessments are planned at screening, baseline, Week 4, Week 12, and Week 24. Safety follow-up will be conducted after the last dose of upadacitinib. Laboratory monitoring will include complete blood count, hepatic and renal function, serum lipids, creatine kinase, and other clinically indicated assessments. Participants will be screened for tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus infection, pregnancy, and relevant cardiovascular or thromboembolic risks before treatment. The primary objective is to estimate the proportion of participants achieving a Hidradenitis Suppurativa Clinical Response of at least 50% at Week 24. Secondary and exploratory analyses will evaluate higher response thresholds, changes in disease activity, patient-reported outcomes, treatment persistence, dose modification, safety outcomes, and potential baseline predictors of treatment response.