Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients (vol 317, 280, 2025)

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.