Introduction: Type II refractory celiac disease (RCD2) is a severe complication of celiac disease characterized by clonal expansion of aberrant intraepithelial lymphocytes (IELs) and risk of enteropathy-associated T-cell lymphoma. Interleukin-15-mediated JAK/STAT activation is central to its pathogenesis and represents a therapeutic target [1–4]. Ruxolitinib inhibits JAK1/2 [5], while preliminary evidence supports JAK inhibition with tofacitinib in RCD2 [6]. We report the first RCD2 case series treated with ruxolitinib.
Methods: Two patients with confirmed RCD2, refractory to budesonide open capsule with or without azathioprine, received off-label ruxolitinib and were prospectively followed. Disease activity was assessed by video capsule endoscopy and double-balloon enteroscopy with histology, quantification of aberrant IELs, and T-cell receptor clonality. Quality of life was evaluated using the SF-36 questionnaire at baseline and 6, 12, and 24 months [7].
Results: Both patients achieved rapid, sustained clinical improvement, including weight gain, resolution of diarrhoea, and normalization of laboratory parameters. One patient discontinued parenteral nutrition within three months. Endoscopy demonstrated reduced extent of villous atrophy and transient normalization of mucosal architecture. Aberrant IELs decreased from 39% to <1% at 24 months in one patient and from 30% to 10% in the other; polyclonal T-cell receptor rearrangement was restored in one case. Unlike previous short-term tofacitinib data [7], ruxolitinib produced a sustained immunological response. SF-36 scores improved across all domains: physical functioning increased from 60.0 to 100, vitality from 32.5 to 80.0, emotional well-being from 50.0 to 82.0, social functioning from 62.5 to 100, pain from 87.5 to 100, and general health from 55.0 to 80.0. No treatment-related adverse events occurred.
Conclusion: Ruxolitinib was associated with clinical, endoscopic, immunological, and quality-of-life improvements, with steroid- and parenteral nutrition-sparing effects. These findings support further evaluation of JAK inhibition as targeted therapy for RCD2.