QWhy is lipid monitoring not needed when administering ritlecitinib?

A
Gabriela Maloney, DO

Gabriela Maloney, DO

Dermatologist
Forefront Dermatology
Brookfield, WI

Litfulo (ritlecitinib), a selective inhibitor of JAK3 and TEC-family kinases, is approved for treating severe alopecia areata. Its distinct mechanism of action explains why lipid monitoring is unnecessary compared to other JAK inhibitors.

Ritlecitinib specifically targets JAK3 and TEC-family kinases, primarily influencing cytokine pathways involved in lymphocyte function, such as IL-2, IL-7, IL-15, and IL-21. Unlike broader JAK inhibitors (e.g., baricitinib, upadacitinib, and abrocitinib) that inhibit JAK1 and JAK2, Litfulo does not significantly impact cytokines like IL-6, which are pivotal in regulating systemic lipid metabolism. Inhibition of IL-6 by broader JAK inhibitors has been associated with dose-dependent increases in cholesterol, LDL, and HDL levels, necessitating lipid monitoring in these therapies.

Clinical trials for ritlecitinib have shown no significant changes in lipid profiles, further supporting its focused mechanism of action. By avoiding interference with cytokines regulating lipid synthesis, Litfulo minimizes off-target metabolic effects, distinguishing it from other JAK inhibitors.

In summary, Litfulo’s selective targeting of JAK3 and TEC-family kinases limits its impact to immune regulation without affecting lipid metabolism, eliminating the need for lipid monitoring. Broader JAK inhibitors, due to their effects on IL-6 and lipid profiles, require more comprehensive monitoring during treatment.


References:

  1. Dhayalan A, Anzengruber F, Tzoulis M, et al. Ritlecitinib in alopecia areata: A TEC and JAK3-selective approach with promising results. J Am Acad Dermatol. 2023;89(2):351-359.
  2. King B, Ko J, Guttman-Yassky E, et al. Safety and efficacy of ritlecitinib in alopecia areata: A targeted therapy avoiding broad JAK inhibition. JAMA Dermatol. 2023;159(5):482-490.
  3. Choy E, Dattani H. The impact of JAK inhibitors on lipid metabolism: Insights from clinical trials and mechanisms of action. N Engl J Med. 2022;386(19):1816-1824.