Review Explores Abrocitinib’s Off-Label Uses

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Abrocitinib is an oral small-molecule inhibitor of janus kinase (JAK) 1, specifically designed for the treatment of moderate to severe atopic dermatitis (AD). Approved in Europe in 2021 for adults and adolescents aged 12 and older, it received FDA approval in January 2022.^1-2 Abrocitinib exhibits notable selectivity for JAK1, being 28-fold more selective than JAK2, over 340-fold more than JAK3, and 43-fold more than tyrosine kinase 2 (TYK2) in biochemical assays. In cellular contexts, it primarily targets the cytokine-induced phosphorylation of STAT proteins linked to JAK1, while minimizing interference with JAK2 signaling pathways.

According to researchers behind a recent review, the clinical implications of abrocitinib's selective inhibition of JAK1 remain uncertain. In placebo-controlled trials lasting up to 16 weeks, patients with moderate to severe AD experienced dose-dependent reductions in platelet counts, peaking around week 4 before trending back toward baseline. JAK inhibitors, including abrocitinib, are becoming increasingly popular in dermatology for their potential to manage both local and systemic inflammation, and have shown promise in treating various skin disorders beyond AD. Given their importance in various inflammatory and immune-mediated diseases, reports of abrocitinib’s off-label use for other conditions have been limited since its approval. With this in mind, the review aims to compile these instances to aid clinicians in considering abrocitinib when standard treatments fail.³

Methods

This study aims to analyze available literature on the off-label use of abrocitinib for conditions beyond AD. The review was conducted by searching the PubMed database for studies published before August 1, 2024, using the search term “abrocitinib.” Initially, articles were screened by title, excluding duplicates and those related to AD. Subsequent screenings of abstracts further removed articles focused on AD, and full-text articles were assessed for eligibility, ensuring they exclusively addressed abrocitinib's use in other skin disorders. Each eligible article was independently reviewed for data extraction.

Results

The review analyzed 281 articles on the off-label use of abrocitinib, narrowing down to 37 relevant papers that focused on its application beyond AD. After excluding ineligible studies, the review highlighted that the majority of the analyzed studies were case reports or small case series, which limited the generalizability of the results. Among the 37 studies, the most frequently documented off-label uses included vitiligo and hand eczema, with 12 cases each. Researchers stated that other notable applications included prurigo nodularis and chronic pruritus of unknown origin, with 12 and 10 cases, respectively.

Researchers wrote that while abrocitinib showed promising outcomes across the conditions, including significant repigmentation in vitiligo and high rates of lesion clearance in hand eczema, the small sample sizes and lack of rigorous controls hinder definitive conclusions. Adverse effects were reported in 19 out of 103 patients, primarily mild and transient, such as headache, nausea, and gastrointestinal discomfort. None of which necessitated treatment discontinuation.

Conclusion

The review stated that abrocitinib may be a promising treatment for various dermatological conditions beyond AD. However, it highlights significant limitations in the current evidence, as most data come from case reports and small series, making it difficult to generalize findings regarding its safety and efficacy. Researchers stated that these initial results should be approached with caution.

They suggested that future research should focus on large-scale, randomized controlled trials to better understand abrocitinib's long-term effectiveness and safety, as well as its comparison to standard treatments. Such studies are essential to validate early observations and expand abrocitinib's role in dermatological practice. Until more robust evidence is available, the review advised clinicians to use careful judgment when considering its off-label use, recognizing its exploratory nature.

References

1. European medicines agency committee for medicinal products for human use (CHMP) summary of opinion: CIBINQO (Abrocitinib). Accessed on October 2, 2024. https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-opinion-cibinqo_en.pdf
2. Pfizer U.S. FDA approves pfizer’s CIBINQO® (Abrocitinib) for adults with moderate-to-severe atopic dermatitis. Accessed on October 2, 2024. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-cibinqor-abrocitinib-adults
3. Mitroi GG, Mitroi GF, Ică OM, et al. Off-label uses of abrocitinib: Review of emerging therapeutic applications beyond atopic dermatitis. Life (Basel). 2024;14(9):1127. 2024. doi:10.3390/life14091127