Comparative effectiveness and safety of upadacitinib, abrocitinib and dupilumab in treatment-resistant prurigo nodularis.

BACKGROUND

Real-world data comparing dupilumab vs. Janus kinase (JAK)1 inhibitors for refractory prurigo nodularis (PN) are limited.

OBJECTIVES

To compare the effectiveness and safety of dupilumab, abrocitinib and upadacitinib in refractory PN.

METHODS

We conducted a retrospective cohort study of adults with refractory prurigo nodularis (PN). This was defined as no response to at least two systemic therapies, Peak Pruritus Numerical Rating Scale (PP-NRS) ≥ 7 and at least 20 nodules. Patients received dupilumab 300 mg every 2 weeks (n = 12), abrocitinib 200 mg daily (n = 8) or upadacitinib 30 mg daily (two doses of 15 mg, n = 8). Follow-up assessments were conducted at weeks 12 (n = 28), 24 (n = 22) and 36 (n = 15). Primary outcomes were changes in PP-NRS and nodule count. Secondary outcomes included changes in Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) scores.

RESULTS

Patients receiving dupilumab were older and had a longer disease duration and higher IgE levels (all P ≤ 0.002). By month 6, a ≥ 4-point reduction in PP-NRS was achieved by 56% of patients on dupilumab, 86% on abrocitinib and 100% on upadacitinib. Nodule reduction by ≥ 50% was seen in 11%, 100% and 100%, respectively. DLQI ≥ 9-point improvement was seen in 33%, 86% and 83%, respectively. HADS scores decreased in all groups, mostly so with upadacitinib. Adverse events included acne (n = 4), creatinine kinase elevation (n = 3), injection-site reaction (n = 2) and herpes zoster (n = 2). No cases of major adverse cardiovascular events, venous thromboembolism, malignancy, serious infection, death or discontinuation occurred.

CONCLUSIONS

In a small, imbalanced multicentre cohort, JAK1 inhibitors showed faster itch relief and greater lesion clearance signals than dupilumab, with meaningful improvements in quality of life.