Systematic Review and Meta-analysis

Efficacy and Safety of Early Biologic Treatment in Adult and Paediatric Patients With Crohn's Disease

Ryan C Ungaro; Saurabh Aggarwal; Ozlem Topaloglu; Wan-Ju Lee; Ryan Clark; Jean-Frederic Colombel


Aliment Pharmacol Ther. 2020;51(9):831-842. 

In This Article

Abstract and Introduction


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.


Crohn's disease (CD) is a chronic, disabling and progressive inflammatory disease of the gastrointestinal tract.[1–3] Chronic inflammation is associated with accumulation of tissue damage that can lead to disease complications such as strictures, fistulae and surgical resections.[4–6] Up to half of patients with CD will experience a disease complication requiring surgery within 10 years of diagnosis.[7]

The treatment paradigm has shifted to a treat-to-target approach in CD in which endoscopic healing is paramount to improve remission rates and long-term risk of complications.[8] Despite their higher efficacy, biologics are often used as a later line of therapy for Crohn's disease (CD), after steroids, 5-ASA or thiopurines.[9,10] There is an increasing volume of evidence suggesting that early use of biologics can improve rates of remission and disease complications.[11–17] Despite these data, the rates of early adoption of biologic therapy are quite low in real-world practice.[18] Therefore, we conducted a systematic review and meta-analysis of the current available data on the impact of early biologic use in CD.