Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD. Objective: We aimed to explore the potential effect of ritlecitinib on CeD serology levels before and after ritlecitinib treatment in research participants of clinical trials. Methods: The effect of ritlecitinib on CeD serology (tTG-IgA, DGP-IgA/IgG) levels was retrospectively evaluated in participants from three phase 2 and one phase 3 ritlecitinib clinical trials including participants with active AA, rheumatoid arthritis (RA) and vitiligo, whose serum samples at baseline and post-treatment were available. All statistical comparisons of the changes between initial and follow-up samples used the Wilcoxon matched pairs exact test. Results: Of 1146 research participants, 21 individuals had a positive tTG-IgA in their baseline samples (positivity rate, 0.018, 95% CI = 0.011–0.028). Among these 21 individuals, follow-up samples were available in 15 participants from the ritlecitinib group and in 3 from the placebo group. In follow-up samples, the values of tTG-IgA in the 15 participants treated with ritlecitinib significantly decreased from baseline (p < 0.01), while in the placebo group the tTGA-IgA levels remained close to the baseline values. Conclusion: A decrease in CeD serology levels with ritlecitinib treatment suggests that ritlecitinib may provide beneficial effect in CeD.