Abrocitinib Effective for Patients with Prurigo Nodularis, Chronic Pruritus of Unknown Origin

Shawn Kwatra, MD

Credit: Johns Hopkins Dermatology

Abrocitinib is efficacious and well-tolerated as treatment for adults with prurigo nodularis (PN) or chronic pruritus of unknown origin (CPUO), according to recent findings, though randomized, double-blind, placebo-controlled studies may be necessary to validate these data.¹

These conclusions were the results of a new study conducted to evaluate the drug’s effectiveness and safety profile at a once-per-day, 200-mg dose among those with either prurigo nodularis or CPUO. This new research was led by Shawn G. Kwatra, MD, of the department of dermatology at the University of Maryland School of Medicine in Baltimore.

Kwatra et al. noted that CPUO continues to be less well-understood, though a role for Janus kinase 1 (JAK1) inhibitor in the condition’s pathogenesis was acknowledged as likely given that CPUO patient subsets feature type 2 inflammatory dysregulation and have increased biomarkers such as blood eosinophils and immunoglobulin E.²

“Given the limited therapeutic options for these conditions and the aforementioned rationale for JAK1 inhibition, we initiated a phase 2, open-label clinical trial to evaluate the JAK1 inhibitor abrocitinib in the treatment of patients with PN and CPUO,” Kwatra and colleaugues wrote.¹

Background and Methods

The investigators conducted the phase 2 study as an open-label, single-center, nonrandomized controlled trial in which the effectiveness and safety profile of once-daily, oral abrocitinib was assessed among adult patients with moderate-to-severe prurigo nodularis or CPUO. The team hypothesized that the JAK1 inhibitor could improve pruritus and quality of life substantially among such patients.

From September 2021 - March 2022, the research team recruited their subjects at outpatient dermatology clinics, with eligible individuals being enrolled in the research after meeting the team’s predetermined criteria and undergoing a 4-week screening process. This was followed by a period of treatment lasting 12 weeks as well as 4 weeks of post-treatment meetings for follow-up. No placebo group was included.

Abrocitinib for the trial had been supplied by Pfizer and was approved by the FDA for patients with atopic dermatitis, with the higher dose of 200 mg per-day having been determined for this study. The investigators determined their primary endpoint for measuring efficacy would be the percent change observed in subjects’ weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from the point of baseline to the 12-week mark.

The percentage of participants reporting a 4-point reduction at minimum in their weekly PP-NRS score from the point of baseline to Week 12 and the percent change observed in their Dermatology Life Quality Index (DLQI) scores were identified by the research team as the secondary endpoints.

Subjects were in the age range of 18 - 80, with individuals with prurigo nodularis having been diagnosed within the prior half-year period and having 20 or more lesions across at least 2 anatomical areas of the body. CPUO patients would have to have experienced itch for 6 weeks or more without any identifiable causes.

A PP-NRS score of 7 or more was required by the team among all subjects within the week prior to their screenings. Additionally, self-reported race was collected by the research team.

Findings

Ten total individuals with prurigo nodularis and an average age of 58.6 years were included in the study, all of whom were female. Additionally, there were 10 subjects with CPUO and an average age of 70.7 years, of whom only 2 were reported as female. The investigators determined that the initial mean (SD) PP-NRS score had been 9.2 (1.0) for those with PN and 8.2 (1.2) for those with CPUO.

PP-NRS scores were reported to have decreased by the 12-week mark by 78.3% among those in the PN arm (95% CI, −118.5 to −38.1; P < .001) and by 53.7% among those in the CPUO arm (95% CI, −98.8 to −8.6; P = .01). From initiation to the 12-week mark, the investigators found that 8 out of 10 participants in the PN cohort and 6 out of 10 among the CPUO cohort had an improvement of 4 or more points on the PP-NRS.

The research team noted that both arms had a substantial level of enhancement in their quality of life, indicated by the percentage DLQI score changes (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 team added that the most commonly-reported adverse event had been acneiform eruption, noting that it had been observed among 10% of the subjects.

The investigators also found that there had been no severe adverse events reported among the participants.

“Limitations of this study include its single-center design, a small sample size, and the lack of a placebo group,” they wrote. “The nonrandomized design presented inherent challenges in determining directional causation. In addition, the study sample was not representative of the population in terms of race and sex.”

References

1. ^{Kwatra SG, Bordeaux ZA, Parthasarathy V, et al. Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial. JAMA Dermatol. Published online June 05, 2024. doi:10.1001/jamadermatol.2024.1464.}
2. ^{Roh YS, Khanna R, Patel SP, et al. Circulating blood eosinophils as a biomarker for variable clinical presentation and therapeutic response in patients with chronic pruritus of unknown origin. J Allergy Clin Immunol Pract. 2021;9(6):2513-2516.e2. doi:10.1016/j.jaip.2021.01.034.}