P692 Efficacy and safety of early biologic treatment of Crohn’s disease in adult and paediatric patients: A systematic review

Abstract

Biologics are usually reserved as a later line of therapy for Crohn’s disease (CD). There is an increasing body of evidence supporting early use of biologics to improve outcomes and change the natural course of the disease. A systematic literature review was conducted to assess the efficacy/effectiveness and safety of biologics in the early treatment of CD. The PubMed, Embase and Google Scholar databases were searched for English language papers and conference abstracts published till October 10, 2017. Studies were selected for inclusion if patients initiated biologics within 2 years of a CD diagnosis or if biologics were used before or with immunosuppressants (top-down) in clinical trials, retrospective observational studies, or economic models, based on PRISMA guidelines. Outcome examined included clinical remission (CR), corticosteroid free remission (CSFR), mucosal healing (MH), relapse rate, hospitalisation rate, complications, surgeries, cost-effectiveness, and safety in adult and paediatric populations. Of 2576 search results, 39 references met search criteria: 10 post hoc analyses of RCTs, 1 RCT, 27 observational studies and 1 cost-effectiveness model. A total of 16796 patients were studied, with a median follow-up duration of 64 weeks (range 10–416). In adults, earlier use of biologics was associated with higher rates of CR at week 26 (CD duration < 2 years 54–68%; 2–5 years 47–48%; >5 years 42–44%), CSFR at week 26 (early 60–82%, conventional 36%), MH at week12 (<2 years 44%; 2–5 years 40%; >5 years 21%), hospitalisation-free rate (< 2 years 93%; 2–5 years 90%; >5 years 86%), and lower relapse rate at year 1 (<2 years 34%; ≥2 years 47%), lower risk of bowel strictures or perianal fistulas (hazard ratio [HR] ranged 0.28 to 0.43 in early vs. late group) and fewer surgeries in 2 years (top-down 9%; step-up 12%). In paediatric patients, similar findings were observed for early vs. late use of biologics showing higher rates of 1 year CR (<2 years 62–84%; ≥2 years 45–50%), 1 year CSFR (early 85%; late 55%), and complete MH within 1 year (≤1 year 45%; >1 year 32%), lower rates of relapse (top-down 16–23%; step-up 55–62%) and penetrating complications (HR 0.30 early vs. late group). Serious infection or malignancy rates were similar in early and late groups. A life-time economic model suggested that early biologic use <2 years of CD was more cost-effective than late biologic use. To our knowledge, this is the most comprehensive systematic review on outcomes of early biologic use in CD. Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real-world settings, and is likely cost-effective compared with late biologic use.