Choung Rok Seon, Ramakrishna Jyoti, Pradhan Vivek, King Brett, Guttman-Yassky Emma, Peeva Elena, Murray Joseph A
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology and Hepatology, 200 1st Street SW, Rochester, MN, 55905, USA.
Arch Dermatol Res. 2025 Jan 18;317(1):280. doi: 10.1007/s00403-024-03784-6.
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.
We aimed to explore the potential effect of ritlecitinib on CeD serology levels before and after ritlecitinib treatment in research participants of clinical trials.
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.
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.
A decrease in CeD serology levels with ritlecitinib treatment suggests that ritlecitinib may provide beneficial effect in CeD.
乳糜泻（CeD）已显示出与包括白癜风和斑秃（AA）在内的自身免疫性疾病有关联。芦可替尼，一种JAK3和TEC激酶家族抑制剂，已被批准用于治疗斑秃患者，并且正处于白癜风治疗的后期研发阶段。芦可替尼抑制在CeD发病机制中起作用的细胞毒性T细胞、自然杀伤细胞和B细胞。
我们旨在探讨芦可替尼对临床试验研究参与者在芦可替尼治疗前后CeD血清学水平的潜在影响。
在三项芦可替尼2期和一项3期临床试验的参与者中，回顾性评估芦可替尼对CeD血清学（组织转谷氨酰胺酶IgA[tTG-IgA]、脱酰胺基谷蛋白IgA/IgG[DGP-IgA/IgG]）水平的影响，这些试验包括患有活动性斑秃、类风湿性关节炎（RA）和白癜风的参与者，其基线和治疗后的血清样本可用。初始样本和随访样本之间变化的所有统计比较均使用Wilcoxon配对精确检验。
在1146名研究参与者中，21人在其基线样本中tTG-IgA呈阳性（阳性率为0.018，95%置信区间=0.011-0.028）。在这21人中，芦可替尼组有15名参与者和安慰剂组有3名参与者有随访样本。在随访样本中，接受芦可替尼治疗的15名参与者的tTG-IgA值与基线相比显著降低（p<0.01），而在安慰剂组中，tTGA-IgA水平仍接近基线值。
芦可替尼治疗使CeD血清学水平降低，提示芦可替尼可能对CeD有有益作用。
