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

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. 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. 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 μg/g. Patients’ mean Lichtiger score decreased to 5 at week 0 and 10/15 patients had a Mayo score of ≤1 at week 10. Average CRP levels decreased to 15.9, 5.8 and 3.8 mg/l at weeks 0, 2 and 6, respectively. Mean ESR decreased to 39.9, 37 and 26.1 mm/h at weeks 0, 2 and 6, respectively. Average calprotectin levels were 1024 and 808 μg/g weeks 2 and 6, respectively. At week 20, 14/15 patients are stable and continue to be in remission, with no adverse effects reported from either cyclosporine or vedolizumab to date. One patient was referred to surgery due to recurrence of symptoms. This is the first prospective study of cyclosporine and vedolizumab in steroid-refractory severe UC patients. We demonstrate significant effectiveness and safety of this treatment on week 10 after vedolizumab was started. Further trials are warranted.