Hidradenitis Suppurativa (Acne Inversa)
Conditions
Keywords
Upadacitinib, Janus kinase inhibitor, JAK1 inhibitor, Hidradenitis suppurativa, Acne inversa, Real-world study, HiSCR, IHS4, Refractory hidradenitis suppurativa, Moderate-to-severe hidradenitis suppurativa
Brief summary
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.
Detailed description
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.
Interventions
DRUGUpadacitinib
Upadacitinib will be administered orally once daily for up to 24 weeks. The recommended starting dose is 15 mg once daily. Dose escalation to 30 mg once daily may be implemented according to clinical response, disease severity, safety findings, participant preference, and drug accessibility. Participants will obtain the medication through a physician's prescription and will bear the medication costs according to routine clinical practice.
Sponsors
Peking Union Medical College
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged 18 years or older. 2. 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. 3. Presence of evaluable inflammatory lesions at baseline, allowing assessment of abscess and inflammatory nodule count, IHS4, pain NRS, pruritus NRS, and DLQI. 4. Considered by the investigator to be an appropriate candidate for treatment with upadacitinib in a real-world clinical setting. 5. Willing and able to comply with scheduled visits, laboratory testing, contraceptive requirements, and safety follow-up. 6. 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. 7. Willing to provide written informed consent.
Exclusion criteria
1. A condition requiring urgent treatment, inpatient antimicrobial treatment, extensive surgery, or another emergency intervention that, in the investigator's judgment, makes participation inappropriate. 2. Active serious infection, active tuberculosis, uncontrolled chronic or recurrent infection, or another condition associated with an unacceptable risk of immunosuppression. 3. 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. 4. Clinically significant cytopenia, severe hepatic or renal impairment, or another laboratory abnormality that makes treatment with upadacitinib inappropriate. 5. 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. 6. Pregnancy, breastfeeding, or plans to become pregnant during the study. 7. A participant of childbearing potential who is unable or unwilling to use effective contraception during the study. 8. Known serious hypersensitivity or contraindication to upadacitinib or any component of the formulation. 9. Recent participation in another interventional clinical study or another condition that may interfere with the evaluation of effectiveness or safety. 10. Any unacceptable safety risk or inability to obtain key effectiveness or safety data, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving HiSCR50 at Week 24 | Baseline to Week 24 | HiSCR50 is defined as at least a 50% reduction from baseline in the combined abscess and inflammatory nodule count, with no increase from baseline in the number of abscesses and no increase from baseline in the number of draining tunnels. |
Countries
China
Outcome results
None listed