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Background Patients with Crohn’s disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD. Methods Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0–72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator’s discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods. Results Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn’s Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually. Conclusions Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks. ClinicalTrials.gov ID: NCT01298492.

Background Combining vedolizumab with a rapid-onset drug such as cyclosporine is a novel combination treatment for severe steroid-resistant ulcerative colitis (UC). This prospective study describes the efficacy and safety of cyclosporine in conjunction with vedolizumab in patients with severe, steroid-resistant UC with 1 year of follow-up. Methods Seventeen steroid-resistant UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Clinical and endoscopic response, remission rates, and colectomy-free survival were the primary endpoints. Secondary endpoints included biochemical response and remission with C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin. Results Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab. By week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission. At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission. Among the 10 patients in endoscopic remission, 8 (80%) reached histological remission. Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively. No serious adverse events were reported. Conclusions Bridging cyclosporine to vedolizumab in severe, steroid-refractory UC patients is effective and safe at inducing and maintaining clinical, endoscopic, and biochemical response and remission up to 52 weeks of follow-up. Larger prospective studies are warranted.

Background Responders to induction treatment sustain continuous clinical response (CCR) through 1 year in about 50% of patients in PURSUIT-M trial with golimumab maintenance in ulcerative colitis (UC). This post hoc analysis of PURSUIT-M describes the 1-year clinical, endoscopic, quality of life (QoL), and biomarker and 4-year clinical outcome in patients with sustained response to golimumab therapy for UC. Methods We compared clinical, endoscopic, QoL, and calprotectin outcomes in CCR and non-CCR patients through 54 weeks in PURSUIT-M. Persistence on golimumab therapy and clinical response at 4 years was assessed for CCR and non-CCR patients. The relationship of colectomy with CCR status was determined. Results Among patients receiving golimumab maintenance, greater proportions of patients with vs without CCR at week 54 achieved clinical remission (67.1% vs 1.9%), corticosteroid-free remission (61.6% vs 1.9%), endoscopic remission (Mayo endoscopy score 0 [47.9% vs 1.3%]), and normal QoL (inflammatory bowel disease questionnaire score ≥170 [75.0% vs 24.4%]). CCR but not non-CCR patients maintained normalized calprotectin levels during maintenance. Among patients who entered the long-term extension study, a greater proportion of patients with vs without CCR maintained PGA 0 through week 216 (58% vs 42%). Colectomy was performed in 47 induction nonresponders and in 13 induction responders. None of the patients going onto colectomy achieved CCR through 54 weeks in PURSUIT-M. Conclusions Continuous clinical response is associated with favorable short- and long-term clinical, endoscopic, QoL, and biomarker responses that may result in changing the course of disease and may prevent colectomy in patients with moderate to severe UC treated with golimumab. 10.1093/ibd/izy229_video1izy229.video15806022773001.