DOP049 Combination therapy of cyclosporine and vedolizumab is effective and safe for severe, steroid-resistant ulcerative colitis patients: A prospective study

Abstract

Background: Vedolizumab is an anti-integrin monoclonal antibody approved for use in moderate to severe ulcerative colitis (UC). However, concurrent use of calcineurin inhibitors was not studied in the original clinical trials, but has subsequently been described. Here we describe the efficacy and safety of cyclosporine in conjunction with vedolizumab for severe, steroid-resistant UC. Method(s): This is a prospective study of 17 UC patients treated with cyclosporine in conjunction with vedolizumab at the Military Medical Academy in Belgrade, Serbia. UC patients, not responding to IV steroids for 3 days were treated with IV cyclosporine at doses of 2 mg/kg titrated to goal trough level of 300-400. At day 8 after IV cyclosporine was started (defined as week 0), those who responded were given vedolizumab 300 mg IV. After vedolizumab was administered, cyclosporine was continued orally at double the IV dose and discontinued after 8 weeks of cyclosporine use. Vedolizumab was dosed 300 mg at weeks 2 and 6, followed by 300 mg IV every 8 weeks. Patients completed initial follow-up including colonoscopy at week 10. Demographics and disease information were collected. Lichtiger score (at admission and week 0), the Mayo endoscopic subscore, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and calprotectin levels were followed at baseline and at various pre-defined times of follow-up. Result(s): Seventeen patients (mean age 40 (20-67 years); mean disease duration 4.9 +/- 4 years with severe, steroid-resistant UC were treated with cyclosporine. Two patients did not respond to IV cyclosporine and were referred to surgery. Fifteen patients (9/15 male) responded to IV cyclosporine (median cyclosporine dose 200 mg (100-300) IV and 400 mg (200-600) oral. At admission, patients' median Lichtiger score was 12 and the Mayo score was 3. Average level of CRP was 21.8 mg/l, ESR was 51.2 mm/h and calprotectin was 1947 mug/g. Patients' mean Lichtiger score decreased to 5 at week 0 and 10/15 patients had a Mayo score of