Efficacy and safety of ustekinumab in the induction therapy of TNF-α-refractory Crohn's disease patients: a systematic review and meta-analysis.

AIM: The aim of the systematic review and meta-analysis was to assess the efficacy and safety of ustekinumab in the induction therapy of anti-TNF-α failure patients with Crohn's disease.

METHODS: A systematic literature search was conducted in Medline (PubMed), EMBASE, Cochrane Library until 30 December 2016. We included randomized controlled trials that compared efficacy (clinical response and remission) and safety profile of ustekinumab in TNF-α failure Crohn's disease patients; primary and secondary TNF-α nonresponders or intolerant patients were also assessed. Included studies were critically appraised according to the PRISMA statement protocol; data aggregation with a RevMan(®) software was performed.

RESULTS: Three randomized controlled trials were revealed in the systematic review but only two of them (CERTIFI and UNITI-1) were homogenous to be included in the meta-analysis; aggregation of data only for induction phase of therapy was possible. Clinical response was significantly higher for patients who received ustekinumab compared with placebo patients in a group of TNF-α antagonist failure patients (relative benefit [RB] = 1.62; 95% CI: 1.28-2.04) and in the following subgroups: secondary nonresponders (RB = 1.98; 95% CI: 1.49-2.63), intolerant patients (RB = 1.47; 95% CI: 1.01-2.13) and patients who failed at least two TNF-α antagonists (RB = 2.19; 95% CI: 1.53-3.14) but in case of primary nonresponders it occurred insignificant (RB = 1.22; 95% CI: 0.76-1.98). The clinical remission in TNF-α antagonist failure population was significantly higher for patients who received ustekinumab compared with placebo (RB = 1.72; 95% CI: 1.17-2.53). Pooled analysis revealed that risk of adverse events in induction phase of therapy was not significantly different (risk ratio = 0.96; 95% CI: 0.86-1.06) between ustekinumab and placebo groups.

CONCLUSION: The clinical response was significantly higher for TNF-α antagonist failure patients who received ustekinumab as well as in subgroups of secondary nonresponders or intolerant patients but not in case of primary nonresponders. Ustekinumab occurred as safe as placebo in the induction as well as in a maintenance phase of therapy.