The Role of JAK Inhibitors in the Treatment of Autoimmune and Autoinflammatory Diseases

According to the Autoimmune Association, an estimated 50 million individuals in the US are living with one or more autoimmune diseases, and the number of individuals diagnosed each year continues to grow.¹ In the past few decades, ongoing research efforts have gained a greater understanding with regard to the pathophysiologies of various autoimmune diseases and have resulted in the development of targeted therapies that address the underlying mechanisms that contribute to the manifestation of these diseases and have improved clinical outcomes in the patients who live with autoimmune and autoinflammatory diseases.

Research has established that Janus kinase/signal transduction and activator of transcription (JAK–STAT) signaling pathway is responsible for the pathogenesis of various inflammatory and autoimmune diseases.² Janus kinase inhibitors (JAK) inhibitors are a growing pharmacological class of drugs with proven efficacy and safety for treating autoimmune and inflammatory diseases and certain types of cancer.^2-4 Available JAK inhibitors comprise 4 members: JAK1, JAK2, JAK3, and TYK2, which vary in their selectivity for specific JAK isoforms and can be nonselective or highly selective.^2-4

In 2011, the FDA approved ruxolitinib as the first JAK inhibitor, and subsequently, in years to follow, the FDA approved additional JAK inhibitors such as tofacitinib, baricitinib, upadacitinib, filgotinib, pacritinib, abrocitinib, and several JAK inhibitors are being explored in clinical trials for the treatment of various conditions.⁴ Depending upon the JAK inhibitors, these agents are approved for the treatment of atopic dermatitis (AD), psoriasis, alopecia areata (AA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and most recently, vitiligo.^2-4

While the majority of JAK inhibitors are available in oral formulations, in July 2022, the FDA approved ruxolitinib cream 1.5% as the only topical formulation of a selective Janus kinase (JAK1/JAK2) inhibitor approved in the US, marking the first and only FDA-approved treatment for repigmentation in adults and pediatric patients 12 years and older for the treatment of nonsegmental vitiligo.⁵ In September 2021, this agent was also approved as a short-term and noncontinuous chronic topical treatment of mild to moderate atopic dermatitis (AD) for individuals 12 years of age and older who are not immunocompromised and whose disease is not satisfactorily controlled with topical prescription therapies, or when those therapies are not recommended.⁵

A recent study exploring published clinical reports regarding topical JAK inhibitors for treating vitiligo revealed that preliminary reports imply that topical JAK inhibitors are a safe and well-tolerated therapy for patients with vitiligo compared to other standard topical treatments.⁶

In a recent publication in Indian J Dermatol Venereol Leprol,⁷ the authors reviewed JAK inhibitors and their roles in treating and managing immune-mediated dermatological conditions. The authors indicated that the efficacy of JAK inhibitors is well-established for a variety of inflammatory and autoimmune diseases. They wrote, “Janus kinase inhibitors have brought another paradigm shift in respect to therapy for autoimmune diseases. In the coming 10 years, this new field of knowledge is going to unfold and hopefully lead to broader use of Janus kinase inhibitors in an array of autoimmune and inflammatory diseases.”⁷

A recent publication in JAMA Network Open suggested that individuals who had COVID-19 are at increased risk of developing autoimmune and autoinflammatory connective tissue disorders, and researchers indicate that this may contribute to an increase in the incidence of these types of diseases.⁸ These findings highlight the need to expand awareness about screening for autoimmune and autoinflammatory diseases and initiating appropriate therapy early on to reduce complications and improve outcomes.

Conclusion

The availability of therapies targeting the underlying pathophysiologies of a disease, such as using JAK inhibitors, has been beneficial for many patients diagnosed with various autoimmune and inflammatory conditions. The selection of these agents should involve shared decision-making between the patient and the prescriber. Treatments should also be tailored to patient needs based on various factors, including other comorbidities, contraindications, and a review of the patient’s medication history to avoid potential drug/drug interactions. Patients should also be aware of the recommended screening and laboratory evaluations needed before therapy is initiated. Patients should also be educated on therapy goals, treatment expectations, potential adverse effects, warnings and precautions, monitoring parameters, and the importance of adherence to prescribed therapy and routine monitoring to enhance clinical outcomes.

References

1. About autoimmunity. Autoimmune Association. 2023. Accessed December 14, 2023. https://autoimmune.org/resource-center/about-autoimmunity/
2. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT Signaling as a target for inflammatory and autoimmune diseases: Current and future prospects. Drugs. 2017;77(5):521-546. doi:10.1007/s40265-017-0701-9
3. Cohen S. Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders. UpToDate. November 2023. Accessed December 12, 2023. https://www.uptodate.com/contents/overview-of-the-janus-kinase-inhibitors-for-rheumatologic-and-other-inflammatory-disorders#H2667659083
4. Shawky AM, Almalki FA, Abdalla AN, Abdelazeem AH, Gouda AM. A comprehensive overview of globally approved JAK inhibitors. Pharmaceutics. 2022;14(5):1001. doi:10.3390/pharmaceutics14051001
5. FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older. FDA.gov. Published July 19, 2022. Accessed December 12, 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older
6. White C, Miller R. A literature review investigating the use of topical Janus kinase inhibitors for the treatment of vitiligo. J Clin Aesthet Dermatol. 2022;15(4):20-25.
7. Raychaudhuri SP, Raychaudhuri SK. JAK inhibitor: Introduction. Indian J Dermatol Venereol Leprol. 2023;89:688-90.
8. Lim SH, Ju HJ, Han JH, et al. Autoimmune and autoinflammatory connective tissue disorders following COVID-19. JAMA Netw Open. 2023;6(10):e2336120. doi:10.1001/jamanetworkopen.2023.36120