Safe and Effective: Upadacitinib Shows Promise in PN Treatment

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Prurigo nodularis (PN) not only presents significant physical discomfort but also leads to a marked decline in quality of life (QoL) due to the persistent nature of the pruritus and the resultant scratching.¹ Although PN is often linked to dermatological issues like atopic dermatitis (AD) and allergic reactions, it is also associated with systemic disorders including diabetes mellitus, chronic renal failure, and various psychiatric conditions.² The persistent itch-scratch cycle in PN complicates treatment efforts, as scratching exacerbates the condition, perpetuating inflammation and discomfort.

Current therapeutic strategies for PN primarily target the management of itch to break the itch-scratch cycle. However, traditional treatments often yield limited success. Upadacitinib, a selective Janus kinase (JAK) 1 inhibitor, has demonstrated rapid pruritus relief in patients with refractory moderate to severe AD and shows potential for treating chronic pruritus of other origins. A recent study aimed to assess the efficacy and safety of upadacitinib in patients with refractory PN, finding that the drug appears to be a well-tolerated and promising treatment option.³

Materials and Methods

The study enrolled 10 patients diagnosed with refractory PN between 2021 and 2023. Inclusion criteria required a clinical or histological diagnosis of PN, age ≥18, and limited response to conventional systemic immunosuppressants for a minimum of 12 weeks.Patients received upadacitinib at a daily dose of 15 mg for 24 weeks. Previous immunosuppressive treatments were discontinued, while any ongoing medications for systemic conditions were maintained.

Treatment response was evaluated using the itch Numeric Rating Scale (NRS), Investigator’s Global Assessment of PN (IGA PN), and Dermatology Life Quality Index (DLQI) at baseline, 4, 12, and 24 weeks. Adverse events were monitored throughout the study.

Results

The study comprised 10 patients (6 men, 4 women) with a median age of 53 years. The mean duration of PN was 5.1 years, with prior treatments including systemic corticosteroids and methotrexate. At baseline, patients exhibited severe pruritus and significant impairment in QOL.

Researchers reported all patients tolerating upadacitinib well, with no medication alterations required. Significant reductions in itch NRS, IGA PN, and DLQI scores were observed at each assessment interval. Specifically, the study found the mean itch NRS score decreased from 8.1 at baseline to 0.7 by week 24, indicating a marked reduction in pruritus. The proportion of patients achieving an IGA PN score of 0/1 rose from 0% at baseline to 80% by week 24.Notably, researchers wrote that all patients reported improved QOL, transitioning from severe impairment at baseline to minimal impairment by week 24.

Overall, researchers reported no serious adverse effects. One patient developed dyslipidemia, which was managed with medication. The study reported all laboratory values remained stable throughout the treatment period.

Conclusion

According to researchers, the study’s findings align with existing literature that suggests JAK inhibitors, including upadacitinib, are effective in managing pruritus and improving skin lesions in PN. While previous studies, including those with tofacitinib, have also shown promising results, researchers found the unique profile of upadacitinib positions it as a valuable therapeutic option, especially in patients with diverse etiologies of PN.

The study suggested that upadacitinib is a well-tolerated and effective treatment for patients with refractory PN. With significant improvements in pruritus and quality of life, upadacitinib offered a compelling alternative for patients who have not responded adequately to conventional therapies. Researchers suggested that future larger-scale studies are warranted to further elucidate its role in the management of PN and to solidify its place in therapeutic protocols.

References

1. Janmohamed SR, Gwillim EC, Yousaf M, et al. The impact of prurigo nodularis on quality of life: a systematic review and meta-analysis. Arch Dermatol Res. 2021;313(8):669-677. doi:10.1007/s00403-020-02148-0
2. Pereira MP, Hoffmann V, Weisshaar E, et al. Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study. J EurAcad Dermatol Venereol. 2020;34(10):2373-2383. doi:10.1111/jdv.16309
3. Lee J, Kim Y, Shin K, et al. Treatment with upadacitinib in refractory prurigo nodularis: A prospective cohort study. Allergy Asthma Immunol Res. 2024;16(5):546-554. doi:10.4168/aair.2024.16.5.546