Systematic review and meta-analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn's disease

Abstract

Background: There is an increasing body of evidence showing that earlier use of biologics improves clinical outcomes in Crohn's disease (CD).

Aim: To perform a systematic review and meta-analysis to assess the impact of early biologic use in the treatment of CD.

Methods: PubMed and Embase databases were searched for English language papers and conference abstracts published through April 30, 2019. Studies were selected for inclusion if patients initiated biologics within 2 years of a CD diagnosis or if earlier biologics use (top-down) was compared with a conventional step-up strategy. Random-effects meta-analyses were conducted to compare clinical remission (CR), relapse and endoscopic healing rates between early biologic treatment (<2 years of disease duration or top-down treatment strategy) and late/conventional treatment (biologic use after >2 years of disease duration or conventional step-up treatment strategy).

Results: A total of 3069 records were identified, of which 47 references met the selection criteria for systematic review. A total of 18 471 patients were studied, with a median follow-up of 64 weeks (range 10-416). Meta-analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 [95% CI: 1.69-2.60], n = 2763, P < .00001), lower relapse rates (OR 0.31 [95% CI: 0.14-0.68], n = 596, P = .003) and higher mucosal healing rates (OR 2.37 [95% CI: 1.78-3.16], n = 994, P < .00001) compared with late/conventional management.

Conclusions: 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.

Figure 1.

PRISMA Diagram of Study Screening and Selection

Figure 2.

Meta-Analysis Comparing Clinical Remission Rates for Early Biologic versus Late/Conventional Treatment Notes: Definition of clinical remission: three studies used CDAI<150^{, ,}; one study used CDAI<150 plus no bowel resection and no steroid use; two studies used PCDAI≤10^,; one study used corticosteroid free remission and PCDAI ≤10 at 1 year after diagnosis without luminal resection; one study did not provide definition of clinical remission

Figure 3.

Meta-Analysis Comparing Relapse Rates for Early Biologic versus Late/Conventional Treatment Definition of disease relapse: One study used increase in CDAI≥70 and an absolute CDAI>220; three studies used PCDAI>10^–

Figure 4.

Meta-Analysis Comparing Mucosal Healing (MH) Rates for Early Biologic versus Late/Conventional Treatment Definition of endoscopic healing: one study used SES-CD=0; one study used CDEIS<4 and absence of deep ulcers; one study used absence of any mucosal ulcers (including aphthous ulcers); one study used absence of mucosal ulceration; one study used absence of ulcers and/or erosions; one study used disappearance of ulcerations, multiple erosions, bleeding and friability (grade 0 or 1); one study did not report definition