Abstract Background Although several therapeutic strategies exist for the treatment of Ulcerative colitis (UC), their efficacy is still far from optimal. The JAK/STAT signalling pathway has emerged as a promising therapeutic target. Tofacitinib (TOFA), an oral JAK inhibitor, is the first approved small molecule for the induction and maintenance of remission in moderate-severe UC. However, potential predictive markers for therapeutic response to TOFA are currently lacking. Therefore, we aimed to assess the mucosal expression of JAK/STAT and cytokine levels in UC patients treated with TOFA to identify potential predictive markers of therapeutic response. Methods This prospective study included patients with UC who initiated TOFA therapy. Clinical indices, laboratory parameters, and colonoscopy were evaluated at baseline and after a 12-week treatment period. RNA and total protein were isolated from colonic biopsies. qRT-PCR was applied for the investigation of the JAK/STAT signalling pathway. Mucosal protein levels of TNF-a, IL-6, IL-1b, IL-4, IL-17A, IFN-g, and PAI-1 were determined by multiplex ELISA. Results A total of 49 patients with UC were enrolled, with 75.5% completing the 12-week follow-up. Among these, 63.3% responded to TOFA. The clinical and endoscopic remission rates were 69.4% and 32.6%, respectively. Primary non-response was identified in 24.5% of patients, while 36.7% experienced loss of response. In responders, serum CRP levels as well as pMayo and eMayo scores decreased significantly. TOFA responders also showed significant downregulation of STAT1 and JAK2 gene expression. Mucosal protein levels of IL-6, IL-1β, IFN-γ, IL-17A, and PAI-1 were markedly reduced in these patients. Baseline concentrations of IL-6, IL-4, and PAI-1 were significantly lower among responders. Patients achieving steroid-free remission exhibited lower baseline levels of IL-1β, IL-4, and PAI-1, whereas elevated IL-1β levels were significantly associated with loss of response. Moderate correlations were detected between pMayo scores and levels of TNF-α, IL-6, IL-1β, and IL-17A, while weaker correlations were observed with eMayo scores. The strongest associations were found between mucosal PAI-1 levels and both pMayo (r = 0.55) and eMayo (r = 0.52) scores. Serum CRP levels showed moderate correlations with cytokine concentrations. Conclusion TOFA treatment proved effective in over 60% of patients, with nearly 70% achieving clinical remission. Lower baseline mucosal protein levels of IL-1b, IL-6, IL-4, and particularly PAI-1, may serve as potential predictors of treatment response. Among these markers, PAI-1 showed the strongest association with both clinical and endoscopic disease activity, highlighting its value as a predictive and monitoring biomarker in UC. Conflict of interest: Dr. Jójárt, Boldizsár: I have no conflict of interest. Resál, Tamás: No conflict of interest Kajári, Lilian: No conflict of interest Bacsur, Péter: No conflict of interest Molnár, Tünde: No conflict of interest Ivány, Emese: No conflict of interest Gémes, Nikolett: No conflict of interest Kemény, Ágnes: No conflict of interest Szebeni, Gábor: No conflict of interest Pallagi, Petra: No conflict of interest Farkas, Klaudia: No conflict of interest Maléth, József: No conflict of interest Molnár, Tamás: Conflict of interest: Tamás Molnár has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, Phytotec, Roche, Fresenius, Teva, Celltrion, Stada, BMS, Ferring, EwoPharma and SOBI
Jójárt et al. (Thu,) studied this question.