Outcomes
death, perianal abscess, congenital anomaly, intestinal obstruction, perianal, bowel damage, fistula, disability
PERIANAL ABSCESS, REMISSIONS, INTESTINAL OBSTRUCTION, ADVERSE EVENTS, ADVERSE EVENT, EVENT, SECONDARY, REMISSION, INFUSION REACTION, INTRA-ABDOMINAL ABSCESS, RELAPSE
There were two coprimary endpoints. The first was relapse rate over 2 years, analysed for superiority. Relapse was defined by a CDAI of 250 or higher at any visit or a CDAI between 150 and 250 with an increase of at least 70 points, over two consecutive visits 1 week apart, and a CRP higher than 5 mg/L or a faecal calprotectin higher than 250 μg/g. A new or reopened perianal or entero-cutaneous fistula, an intra-abdominal abscess (size ≥3 cm) or a perianal abscess (size ≥2 cm), and an episode of intestinal obstruction confirmed by imaging and requiring hospital admission were also considered as relapse.The second coprimary endpoint was the mean restricted time spent in remission during the 104 study weeks, analysed for non-inferiority. For patients who relapsed, this time was computed from the day of randomisation until relapse, and added to the time spent in first and subsequent regained remissions (CDAI <150). Patients failing to recapture remission or fulfilling other definitions of treatment failure terminated the trial and were considered not to be in remission for the remaining weeks of the study (except for the failures linked to treatment side-effects who were censored at the time of failure).Treatment failure was defined as not achieving remission after treatment escalation for relapse according to the protocol, or any major treatment side-effect leading to treatment cessation, or occurrence of an intra-abdominal abscess (size ≥3 cm) or a perianal abscess (size ≥2 cm), or occurrence of intestinal obstruction requiring surgical resection or endoscopic dilatation.The main secondary endpoints were: time to relapse from date of randomisation, factors associated with time to relapse, treatment failure rate, time to treatment failure from date of randomisation and factors associated with time to treatment failure, sustained steroid-free remission (defined as CDAI <150 for all trial visits and no steroid use; patients discontinuing the trial for any reason before week 104 were not considered in sustained steroid-free remission), changes between baseline and end of study visit in hsCRP, faecal calprotectin, CDEIS, SES-CD, infliximab trough levels, and anti-infliximab antibodies. The following additional secondary endpoints are not presented in the present manuscript because they are still being analysed: progression of bowel damage, time to relapse according to CRP and calprotectin value, change in the disability score, health-related quality of life, direct and indirect costs, change in blood hsCRP and faecal calprotectin, change in infliximab trough levels and anti-infliximab antibodies, and correlations between a series of biomarkers (proteomics, glycomics, DNA methylation, miRNA, metagenomics), in the three groups of the study.Adverse events were monitored in all randomised patients during the whole study. Serious adverse events (death, life-threatening hospitalisation and prolongation of hospitalisation, congenital anomaly, spontaneous or elective abortion, significant disability, medical event requiring medical or surgical intervention to prevent serious outcome) were recorded. Adverse events were tabulated by system organ class and preferred term, using the MedDRA dictionary (version 19.0). Incidence and severity of acute or delayed infliximab infusion reactions were assessed according to the Ring and Messmer classification.