EFFICIENCY OF DUAL THERAPY WITH VEDOLIZUMAB AND TOFACITINIB IN REFRACTORY ULCERATIVE COLITIS PATIENTS – SINGLE CENTRE EXPERIENCE

Abstract

Abstract INTRODUCTION Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients. METHODS Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months of treatment. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated. RESULTS In total, 21 ulcerative colitis patients who were started on vedolizumab and tofacitinib dual therapy between October 2020 and September 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons. CONCLUSION In the presented small cohort of patients, however, with refractory and complicated ulcerative colitis in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be very efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.