Konstantinos Papamichael1, Oliviane Rivals-Lerebours2, Thomas Billiet3, Niels Vande Casteele4, Ann Gils4, Marc Ferrante3, Gert Van Assche3, Paul J Rutgeerts3, Gerassimos J Mantzaris5, Laurent Peyrin-Biroulet2, Severine Vermeire6. 1. KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium Evangelismos Hospital, Department of Gastroenterology, Athens, Greece. 2. Nancy University Hospital, Inserm U954 and Department of Gastroenterology, Nancy, France. 3. KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium. 4. KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Leuven, Belgium. 5. Evangelismos Hospital, Department of Gastroenterology, Athens, Greece. 6. KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium severine.vermeire@uzleuven.be.
Abstract
BACKGROUND AND AIMS: We studied the long-term outcome of patients with ulcerative colitis [UC] and primary non response [PNR] to infliximab and searched for predictors of colectomy in these patients. METHODS: This retrospective, multi-centre study included UC patients from three European referral centres, with PNR to infliximab defined as a lack of clinical improvement after the induction therapy, leading to drug discontinuation. Relapse, for patients who continued on biologicals after PNR to infliximab, was defined as drug discontinuation for PNR, loss of response, or serious adverse event. Serum infliximab concentrations at Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA] developed in house. RESULTS: The study population consisted of 99 anti-tumour necrosis factor [TNF]-naïve patients with UC and PNR to infliximab. At the end of follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these patients underwent colectomy. Multiple Cox regression analysis identified acute severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p = 0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p = 0.005], baseline albumin < 40g/l [HR: 9.5; 95% CI: 1.3-71.4; p = 0.026], and infliximab concentration at Week 2 < 16.5 μg/ml [HR: 5.6; 95% CI: 1.1-27.8; p = 0.034] as independent predictors of colectomy. Regarding patients who continued on biologicals after PNR to infliximab, there was a marginally higher cumulative probability for relapse in patients switching to another anti-TNF agent compared with those swapping to vedolizumab [p logrank = 0.08]. CONCLUSIONS: About half of UC patients with PNR to infliximab will undergo colectomy. Patients with severe inflammation and low serum infliximab concetrations during the induction phase are at greatest risk.
BACKGROUND AND AIMS: We studied the long-term outcome of patients with ulcerative colitis [UC] and primary non response [PNR] to infliximab and searched for predictors of colectomy in these patients. METHODS: This retrospective, multi-centre study included UC patients from three European referral centres, with PNR to infliximab defined as a lack of clinical improvement after the induction therapy, leading to drug discontinuation. Relapse, for patients who continued on biologicals after PNR to infliximab, was defined as drug discontinuation for PNR, loss of response, or serious adverse event. Serum infliximab concentrations at Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA] developed in house. RESULTS: The study population consisted of 99 anti-tumour necrosis factor [TNF]-naïve patients with UC and PNR to infliximab. At the end of follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these patients underwent colectomy. Multiple Cox regression analysis identified acute severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p = 0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p = 0.005], baseline albumin < 40g/l [HR: 9.5; 95% CI: 1.3-71.4; p = 0.026], and infliximab concentration at Week 2 < 16.5 μg/ml [HR: 5.6; 95% CI: 1.1-27.8; p = 0.034] as independent predictors of colectomy. Regarding patients who continued on biologicals after PNR to infliximab, there was a marginally higher cumulative probability for relapse in patients switching to another anti-TNF agent compared with those swapping to vedolizumab [p logrank = 0.08]. CONCLUSIONS: About half of UC patients with PNR to infliximab will undergo colectomy. Patients with severe inflammation and low serum infliximab concetrations during the induction phase are at greatest risk.
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