Herpesviridae Reactivation and Therapeutic Outcomes in Patients with Ulcerative Colitis Treated with Tofacitinib

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Historically, anti-tumor necrosis factor (TNFα) agents have been the mainstay of biological therapy. Recently, Janus kinase inhibitors (JAK-I) have emerged as oral alternatives. However, despite their acknowledged efficacy, concerns remain regarding viral reactivation, particularly Herpesviridae viruses. Aims: This study assesses the incidence of Herpesviridae (HSV and VZV) reactivation and the effect on the clinical course of UC patients treated with tofacitinib (JAK-I). Methods: This prospective cohort study monitored 27 UC patients starting treatment with tofacitinib for clinical and inflammatory disease activity using the simple clinical colitis activity index (SCCAI) and fecal calprotectin. Saliva samples from 24 patients were also analyzed by PCR for Herpesviridae reactivation. Follow-up duration for each patient was up to 42 months. The majority of samples (118/172) were collected over the first 12 months of therapy. Results: Clinical remission (SCCAI ≤ 3) was achieved in 48.1% of the patients. Reactivation of HSV and VZV was detected in 33.3% (8/24) and 4.2% (1/24) of tofacitinib-treated patients, respectively, with no symptomatic outbreaks, and in 4.2% (1/24) of patients primarily infected with HSV. Clinical disease activity was not associated with positive or negative HSV in saliva (66.7% vs. 33.3%, respectively, p = 0.21, R = 2.00, 95% CI 0.85-4.69); however, the study was not powered for this comparison. Similarly, the study was unable to detect or exclude an association between calprotectin levels in patients with or without Herpesviridae reactivations (p = 0.87). Conclusions:Herpesviridae virus (HSV/VZV) reactivation under tofacitinib treatment within the study cohort was asymptomatic, and the study was unable to detect or exclude an association with disease activity. No symptomatic herpes zoster reactivation occurred; however, the small cohort cannot exclude a clinically meaningful risk.