Talking About JAKs: Best Practices for Effective Patient Communication

At the 2024 Fall Clinical Dermatology Conference for PAs and NPs, Raj Chovatiya, MD, PhD, FAAD, associate professor at Rosalind Franklin University Chicago Medical School and the founding director of the Center for Medical Dermatology and Immunology Research, and Dermatology Times 2024 Fall Editor in Chief, presented "Talking JAK: Patient Conversations and Best Practices." His presentation focused on understanding Janus Kinase (JAK) inhibitors, discussing their clinical use, safety profiles, and effective patient communication strategies.¹

“We now have so many different therapeutics across different diseases. A big question for many folks who are either reticent or unfamiliar with topical oral JAK inhibitors is ‘why should I use them and how do they work?’ The very broad answer to that question is that JAK-STAT signaling is an important part of many different immunologic pathways that mediate different aspects of our common diseases, atopic dermatitis, psoriasis, alopecia areata, vitiligo, and it's a reason why this has been a very flexible class that has allowed for treatment across multiple different disease spaces,” he said in an interview with Dermatology Times.

Refresher on the Basics

Chovatiya explained the role of JAK proteins in cytokine and growth factor signaling, which is crucial for immune responses and various cellular functions. He used an analogy to help patients understand: JAK proteins are like delivery services (USPS, UPS, FedEx) that carry messages throughout the body. When there are too many messages, it can lead to excessive activity and imbalance, contributing to diseases like atopic dermatitis (AD).

In AD, specific cytokines such as IL-4, IL-13, and IL-31 interact with skin cells, immune cells, and nerves, causing a compromised skin barrier, inflammation, and itchiness.²

Addressing Safety

Chovatiya addressed common safety concerns associated with JAK inhibitors, emphasizing the importance of understanding patient-specific factors. He explained that while JAK inhibitors are generally safe for most patients, certain adverse events (AEs) are more prevalent in specific populations, such as those with rheumatoid arthritis (RA). Key points included:

• Disease Dependency: The risk of AEs varies significantly between diseases, with rheumatologic conditions posing a higher risk compared to dermatologic diseases.
• Patient-Specific Risks: Sociodemographic factors, lifestyle, medical history, and concurrent medications can influence the likelihood of AEs.
• Boxed Warning Context: The boxed warning for JAK inhibitors stems from studies in patients with RA, who often have higher baseline risks for cardiovascular events and infections. This warning may not directly apply to dermatologic patients.³

He reassured that most severe AEs, such as herpes reactivation or infections, are uncommon and manageable.

Approach in Multiple Diseases

Chovatiya shared his practical approach to using JAK inhibitors across multiple dermatologic conditions:

• AD: Oral JAK inhibitors like abrocitinib(Cibinqo; Pfizer)and upadacitinib(Rinvoq; Abbvie) are suitable for patients needing rapid disease control, those with inadequate responses to biologics, or those preferring oral over injectable treatments. He highlighted their rapid efficacy and flexible dosing options.
• Alopecia areata: Baricitinib (Olumiant; Eli Lilly and Company) and ritlecitinib (Litfulo; Pfizer) are recommended for patients with significant hair loss. Chovatiya noted that "severe" can be subjective and should be determined by the patient's perception of their condition.
• Psoriasis: Deucravacitinib (Sotytku; Bristol Myers Squibb), a Tyk2 inhibitor, is preferred for its efficacy among oral treatments. Chovatiya emphasized the importance of aligning treatment with patient preferences and the mode of administration.
• Vitiligo: Topical ruxolitinib (Opzelura; Incyte) is effective, especially for facial and neck areas, often in combination with narrowband UVB therapy.

JAK inhibitors represent an advancement in dermatologic treatment, offering targeted therapies that address the underlying mechanisms of inflammation. Chovatiya stressed the importance of patient-centered communication, ensuring that patients understand their treatment options and potential risks.

“JAK inhibitors offer a unique proposition for the treatment of dermatologic disease based on the biology of JAK/STAT signaling,” Chovatiya concluded. “Understanding target, disease, and patient factors is critical to the safety discussion – if you understand this, you will understand JAKs. Efficacy is not the debate, as each drug offers a way to elevate patient care in the right situation – there is nothing controversial about this. While I expect everyone to have good command of data for medications which they prescribe, the patient conversation is deeper and more challenging than that JAK inhibitors changing the way we treat inflammatory disease in real time – and there is so much more coming.”

References

1. Chovatiya R. Talking JAK: patient conversations and best practices. Presented at: 2024 Fall Clinical Dermatology Conference for PAs and NPs; May 31-June 2, 2024; Scottsdale, AZ.
2. Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6(1):402. Published 2021 Nov 26. doi:10.1038/s41392-021-00791-1
3. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927