Abstract: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias. CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively. CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively. In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

Plain-language summary: The literature was searched up to 28 January 2019. Four studies involving 1485 patients compared certolizumab pegol with placebo (a dummy drug). All studies included patients with active Crohn’s disease. Most patients were adults over 18 years of age, except for six patients aged 16 or 17 years old. All studies were funded by the drug manufacturer. In a combined analysis of the four studies, patients with active Crohn’s disease who received certolizumab pegol at a dose ranging from 100 mg to 400 mg every 2 to 4 weeks, responded to the treatment and achieved remission at 8 weeks more often than patients taking placebo. No remarkable difference in the rate of serious side effects was observed between certolizumab pegol and placebo. Serious side effects included worsening Crohn's disease, infections, and malignancy (i.e. cancer). Moderate certainty evidence suggests that certolizumab pegol is beneficial in terms of achieving remission in people with moderate to severe Crohn's disease. Because of a low number of serious side effects, the certainty of evidence about harms of certolizumab pegol was moderate. Moderate certainty evidence suggests that certolizumab pegol is effective for induction of clinical remission and clinical response in people with active Crohn's disease. It is uncertain whether the risk of serious side effects differs between certolizumab pegol and placebo. Future studies are needed to evaluate the long-term benefits and harms of certolizumab pegol in people with Crohn's disease.