Abstract: Three placebo-controlled RCTs (714 adult participants) were included. The participants had moderate to severely active CD (CDAI 220 to 450). Two studies were rated as at low risk of bias and one study was rated as at unclear risk of bias. Seventy-six per cent (342/451) of adalimumab participants failed to achieve clinical remission at four weeks compared to 91% (240/263) of placebo participants (RR 0.85, 95% CI 0.79 to 0.90; high-certainty evidence). Forty-four per cent (197/451) of adalimumab participants compared to 66% (173/263) of placebo participants failed to achieve a 70-point clinical response at four weeks (RR 0.68, 95% CI 0.59 to 0.79; high-certainty evidence). At four weeks, 57% (257/451) of adalimumab participants failed to achieve a 100-point clinical response compared to 76% (199/263) of placebo participants (RR 0.77, 95% CI 0.69 to 0.86; high-certainty evidence). Sixty-two per cent (165/268) of adalimumab participants experienced an AE compared to 72% (188/263) of participants in the placebo group (RR 0.90, 95% CI 0.74 to 1.09; moderate-certainty evidence). Two percent (6/268) of adalimumab participants experienced a SAE compared to 5% (13/263) of participants in the placebo group (RR 0.44, 95% CI 0.17 to 1.15; low-certainty evidence). Lastly, 1% (3/268) of adalimumab participants withdrew due to AEs compared to 3% (8/268) of participants in the placebo group (RR 0.38, 95% CI 0.11 to 1.30; low-certainty evidence). Commonly reported adverse events included injection site reactions, abdominal pain, fatigue, worsening CD and nausea. Quality of life data did not allow for meta-analysis. Three studies reported better quality of life at four weeks with adalimumab (measured with either Inflammatory Bowel Disease Questionnaire or Short-Form 36; moderate-certainty evidence). Endoscopic remission and response, histologic remission and response, and steroid withdrawal were not reported in the included studies. High-certainty evidence suggests that adalimumab is superior to placebo for induction of clinical remission and clinical response in people with moderate to severely active CD. Although the rates of AEs, SAEs and withdrawals due to AEs were lower in adalimumab participants compared to placebo, we are uncertain about the effect of adalimumab on AEs due to the low number of events. Therefore, no firm conclusions can be drawn regarding the safety of adalimumab in CD. Futher studies are required to look at the long-term effectiveness and safety of using adalimumab in participants with CD.

Plain-language summary: The researchers found three studies with a total of 714 adult (> 18 years) participants. These participants all had moderate to severely active Crohn's disease. A total of 451 participants were treated with adalimumab and 268 were treated with a placebo (a fake medication). More participants who were treated with adalimumab achieved remission or improvement of their symptoms than those who were treated with placebo. The rates of side effects (adalimumab: 62%, placebo: 72%), serious side effects (adalimumab: 2%, placebo: 5%) and study withdrawal due to side effects (adalimumab: 1%, placebo: 3%) were lower in adalimumab participants than placebo participants. Commonly reported side effects included injection site reactions, abdominal pain, fatigue, worsening Crohn's disease and nausea. High-certainty evidence suggests that treating participants with adalimumab is better than treating them with placebo for inducing remission and improving symptoms in people with moderate to severely active Crohn's disease. Side effects were lower in adalimumab participants compared to placebo. However, we are uncertain about the effect of adalimumab on side effects due to the low number of events, therefore, no firm conclusions can be drawn regarding the harms (side effects) of adalimumab in Crohn's disease. Futher studies are required to look at the long-term benefits and harms of using adalimumab in people with Crohn's disease.