What You Need To Know NOW About JAK Inhibitors
Assistant Professor, Director of Center for Eczema and Itch
Northwestern University Feinberg School of Medicine
Janus kinase (JAK) inhibitors are one of the hottest topics in dermatology today. In this session, Raj Chovatiya, MD, PhD, MSCI, reviewed the science behind JAK inhibitor therapy and the latest updates for JAK inhibitors on the market and in development. The Janus kinase family has 4 members: JAK1, JAK2, JAK3, and TYK2. These intracellular molecules play a central role in cell signaling for many different pathways. JAK1 and JAK3 play a role in immunity and metabolism, while TYK2 plays a role in immunity only. JAK2 has the widest range of influence, playing a role in immunity, metabolism, and hematopoiesis.
Currently, there are multiple JAK inhibitors on the market for a wide range of indications. While each JAK inhibitor has distinct chemistry and is generally considered selective for certain JAK molecules, there is overlap and cross-talk between all JAK molecules, leading to class-wide side effects such as infection, cytopenia, and hyperlipidemia. All JAK inhibitors have received a black box warning from the FDA for increased risk of serious infection, malignancy, mortality, thrombosis, and major adverse cardiovascular events, except deucravacitinib which is an oral selective TYK2 inhibitor. Dr Chovatiya discussed these boxed warnings and recent evidence showing no relationship between upadacitinib, a JAK1 inhibitor approved for atopic dermatitis, and increased risks of major adverse cardiovascular events or thrombosis in the atopic dermatitis population.
To conclude, Dr Chovatiya provided updates on the newer JAK inhibitors on the market. Ruxolitinib 1.5% cream, which is approved for atopic dermatitis and vitiligo, was found to decrease itch within 15 minutes of application in a Phase 2 open-label study. Upadacitinib is currently in Phase 3 clinical trials for hidradenitis suppurativa, with 38% of patients on upadacitinib 30 mg daily achieving HiSCR50 at Week 12 regardless of Hurley stage or prior TNF-a inhibitor use. Ritlecitinib, a JAK3/TEC inhibitor, and baricitinib, a JAK1/2 inhibitor, are both FDA approved for severe alopecia areata. Duration and severity of disease are inversely associated with therapeutic response, emphasizing the need for early intervention.