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

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.

Inclusion criteria

• Male or female participants aged 18 years or older.
• Diagnosis of moderate-to-severe hidradenitis suppurativa confirmed by a dermatologist, generally corresponding to Hurley stage II or III, or active hidradenitis suppurativa considered by the investigator to require systemic treatment.
• Presence of evaluable inflammatory lesions at baseline, allowing assessment of abscess and inflammatory nodule count, IHS4, pain NRS, pruritus NRS, and DLQI.
• Considered by the investigator to be an appropriate candidate for treatment with upadacitinib in a real-world clinical setting.
• Willing and able to comply with scheduled visits, laboratory testing, contraceptive requirements, and safety follow-up.
• Able to understand the real-world and exploratory nature of the study and that upadacitinib is an investigational and off-label treatment for hidradenitis suppurativa.
• Willing to provide written informed consent.

Exclusion criteria

• A condition requiring urgent treatment, inpatient antimicrobial treatment, extensive surgery, or another emergency intervention that, in the investigator's judgment, makes participation inappropriate.
• Active serious infection, active tuberculosis, uncontrolled chronic or recurrent infection, or another condition associated with an unacceptable risk of immunosuppression.
• Screening results indicating hepatitis B, hepatitis C, human immunodeficiency virus infection, tuberculosis, or another infection risk that requires postponement of immunomodulatory treatment and makes participation inappropriate.
• Clinically significant cytopenia, severe hepatic or renal impairment, or another laboratory abnormality that makes treatment with upadacitinib inappropriate.
• Previous venous thromboembolism, a serious major adverse cardiovascular event, active malignancy, or another condition for which the investigator considers the risk of a Janus kinase inhibitor unacceptable.
• Pregnancy, breastfeeding, or plans to become pregnant during the study.
• A participant of childbearing potential who is unable or unwilling to use effective contraception during the study.
• Known serious hypersensitivity or contraindication to upadacitinib or any component of the formulation.
• Recent participation in another interventional clinical study or another condition that may interfere with the evaluation of effectiveness or safety.
• Any unacceptable safety risk or inability to obtain key effectiveness or safety data, as determined by the investigator.