Abrocitinib for prurigo nodularis: Clinical efficacy and safety profile

Prurigo nodularis (PN) is a chronic inflammatory skin disorder with severe itching.1 Researchers have found dupilumab, IL-31 inhibitors and JAK inhibitors have good efficacy in the treatment of PN.1-6 Janus Kinase (JAK) inhibitors, which act on neuroinflammatory pathways, represent a potential therapeutic option for PN. To assess the efficacy and safety of abrocitinib, an oral JAK1 inhibitor, in treating PN, we present a series of patients with PN treated with abrocitinib in our centre. We conducted a prospective, 24-week observational cohort study (up to 18 months follow-up). Inclusion criteria were as follows: (1) previously ineffective to conventional treatments and (2) agreed to use abrocitinib. Exclusion criteria included patients with severe comorbidities or a documented history of intolerance or hypersensitivity to abrocitinib. Before the treatment, demographic and clinical characteristics of all patients were collected (Table 1). They were treated with abrocitinib 100 mg qd and reduced the medication gradually depending on the condition (Table 1). Other adjuvant treatments were desloratadine tablets and halometasone cream. The therapeutic response was defined by a reduction of 4 points in the peak pruritus score on the Numeric Rating Scale (NRS).2 NRS scores and the Dermatology Life Quality Index (DLQI) were evaluated at baseline, Week 12 and Week 24. Investigator's global assessment (IGA) of prurigo, IGA-activity scores (IGA-a) and IGA-chronic nodular prurigo (IGA-CNPG) scores were assessed at baseline, Week 8, Week 16 and Week 24. Adverse events were monitored during the treatment. 100 mg, qd/3 months 100 mg, qod/3 months 100 mg, qd/2 months 100 mg, qod/4 months 100 mg, qd/3 months 100 mg, qod/3 months 100 mg, qd/3 months 100 mg, qod/3 months 100 mg, qd/3 months 100 mg, qod/3 months 100 mg, qd/2 months 100 mg, qod/2 months 100 mg, qd/3 months 100 mg, qod/3 months Oral administration of abrocitinib significantly reduced pruritus in patients with PN in a short time, especially within 1 day, and led to sustained control within 24 weeks (Figure 1d). By the end of the first 14-day treatment, the mean NRS score decreased from 8.20 ± 1.55 to 2.20 ± 1.48. At the end of the 24-week treatment, the NRS score continued to decline to 1.22 ± 0.67. The DLQI score decreased from 15.80 ± 2.30 to 5.78 ± 4.27. IGA score dropped from 2.67 ± 0.71 to 1.50 ± 0.55, IGA-activity score dropped from 3.00 ± 0.67 to 1.44 ± 0.73, and IGA-CNPG score dropped from 2.56 ± 0.53 to 1.33 ± 0.71. IGA 0–2 was attained by all patients, and 5 (56%) patients achieved IGA 0/1. One patient (Patient 3) owing to financial constraints discontinued treatment and transitioned to tofacitinib after 8 weeks, while the remaining 9 patients continued the treatment for 24 weeks. One patient (Patient 4) experienced bilateral lower extremity oedema during the second month of treatment with abrocitinib. Consequently, abrocitinib was suspended until adverse reactions, including thromboemboli, related to abrocitinib were ruled out. No other treatment-associated adverse effects or abnormal laboratory findings were noted in the remaining patients receiving abrocitinib. It is hypothesized that the manifestation of pruritus with PN may be linked to factors such as skin nerve fibre density, immune cell infiltration and cytokine expression, particularly involving Th2 cell cytokines.6, 7 Notably, IL-31, a highly pruritic cytokine predominantly expressed by CD4+ Th2 cells, is implicated in perpetuating the relentless itch-scratch cycle by activating JAK 1, JAK 2 and STAT 3, leading to increased itching and prolonged inflammation.6-8 Abrocitinib exerts broad anti-inflammatory effects by activating the JAKi pathway,9 thereby breaking the itch-scratch cycle and having an effect on pruritic diseases. Our study showed that abrocitinib rapidly reduced severe pruritus (NRS scores from 8–9 to 4 within 1 day) and significantly improved vegetated lesions (IGA scores from 4 to 1–2 in 16 weeks), outperforming prior treatments like tofacitinib, baricitinib and upadacitinib.1, 3, 5, 10 Longer follow-up and larger sample sizes are still needed to demonstrate the long-term efficacy of abrocitinib treatment. Beijing Bethune Charitabie Foundation (JJXYZ-LC-01) and Top talent project of Hubei Health Commission. The authors have no conflict of interest to declare. The study protocol was reviewed and approved by the Institutional Ethics Committee of Wuhan No.1 Hospital. The patients in this manuscript have given written informed consent to publication of their case details. The raw data supporting the conclusions of this article will be made available by the corresponding authors.