This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

We aim to conduct a systematic review and meta‐analysis of all RCTs that compare biologic drugs (TNF‐α antagonists, integrin antagonists, or ustekinumab) against placebo or an active comparator in adults with CD. Using frequentist network meta‐analysis, we aim to assess the efficacy of biologic drugs to treat CD and generate a clinically useful ranking of available biological drugs according to efficacy in terms of:

1) Induction and maintenance of clinical remission in CD, defined as a Crohn's Disease Activity Index (CDAI) below 150;

2) Induction and maintenance of clinical response in CD, defined as a drop in the CDAI of at least 70 (CDAI‐70) or 100 (CDAI‐100) points compared to baseline; and

3) Induction of endoscopic remission in CD, defined as an absence of ulceration.