Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease

• Published in: Cochrane database of systematic reviews 2015-05 (5), p.CD007572-CD007572
• Main Authors: Khanna, Reena, Preiss, Jan C, MacDonald, John K, Timmer, Antje
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Crohn Disease - therapy; Humans; Injections, Intravenous; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - immunology; Interleukin-23 - antagonists & inhibitors; Interleukin-23 - immunology; Randomized Controlled Trials as Topic; Remission Induction - methods; Ustekinumab
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD007572.pub2

Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn's disease. The objectives of this review were to assess the efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. The following databases were searched from inception to September 16, 2014: PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL). References and conference abstracts were searched to identify additional studies. Randomized controlled trials (RCTs) trials in which monoclonal antibodies against IL-12/23p40 were compared to placebo or another active comparator in patients with active Crohn's disease were included.  Two authors independently screened  studies for inclusion and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150 points. Secondary outcomes included failure to induce clinical improvement, serious adverse events, and withdrawals due to adverse events. Clinical improvement was defined as decreases of > 70 or > 100 points in the CDAI from baseline. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. A fixed-effect model was used to pool data. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Four randomized controlled trials (n = 955 patients) met the inclusion criteria. A low risk of bias was assigned to all studies. The two briakinumab trials were not pooled due to differences in doses and time points for analysis. In both studies there was no statistically significant difference in remission rates. One study (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In the briakinumab group 70% (44/63) of patients failed to enter clinical remission at 6 or 9 weeks compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65 to 1.14). Subgroup analysis revealed no significant differences by dose. The other briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg and 700 mg with placebo. Eighty-four per cent (154/184) of briakinumab patients failed to enter clinical remission at six weeks compared to 91% (42/46) of placebo patients (RR 0.92, 95% CI 0