Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial

Abstract

Importance: Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.

Objective: To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.

Design, setting, and participants: This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.

Intervention: Abrocitinib, 200 mg, by mouth once daily for 12 weeks.

Main outcomes and measures: The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.

Results: A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.

Conclusions and relevance: The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.

Trial registration: ClinicalTrials.gov Identifier: NCT05038982.

Figure 1.. Participant Flow Diagram

Five patients were screened but not enrolled in the study because of low white blood cell count, low estimated glomerular filtration rate, significant cardiac disease with reduced ejection fraction, significant risk of atherosclerosis with uncontrolled metabolic syndrome, or voluntary departure from the study. Two patients with CPUO were lost to follow-up after week 12 and did not complete the week 16 follow-up visit. CPUO indicates chronic pruritus of unknown origin; PN, prurigo nodularis.

Figure 2.. Clinical Improvement in Patients With Prurigo Nodularis (PN) and Chronic Pruritus of Unknown Origin (CPUO) With Abrocitinib Treatment

Panels A and B show the percent change from baseline in weekly Peak Pruritus Numeric Rating Scale (PP-NRS) scores in the intention-to-treat population. Error bars indicate the standard error of the mean. Panels C and D show the proportion of patients achieving clinically meaningful within-patient improvement in PP-NRS scores compared with baseline. Panels E and F display clinical images of a patient with PN before and after abrocitinib treatment.