Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Background and Aims: We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. Methods: We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn's disease [CD], relapse after anti-tumour necrosis factor-alpha [anti-TNF alpha]de-escalation, and the rate of disease response recapture following re-escalation. Results: Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNF alpha, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. Conclusions: Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years.This risk is more pronounced in patients requiring anti-TNF alpha for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.