Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs

Abstract

Aim: To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). Design: A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). Results: After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. Conclusion: The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

Keywords:

• adalimumab
• golimumab
• infliximab
• network meta-analysis
• ulcerative colitis

Financial & competing interests disclosure

The authors were supported by funding from Janssen Canada. The sponsor contributed to the design of study, but did not have a role in the analysis and interpretation. Kristian Thorlund and Edward Mills are founding partners of Redwood Outcomes, a health economics and outcomes research firm that specialises in network meta-analysis and health economic evaluations. Redwood Outcomes’ client base includes several pharmaceutical and biotech companies. Redwood Outcomes has previously prepared network meta-analysis and cost-effectiveness analyses in ulcerative colitis for Janssen Pharmaceuticals and Merck Sharp & Dohme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Although several indirect comparisons and network meta-analyses have assessed anti-TNFs for ulcerative colitis, only one has included the 1-year outcomes for golimumab in the comparisons [6–9]. However, this analysis did not account for the ‘two-stage re-randomization’ design of the PURSUIT trial.

• We conducted an indirect comparison meta-analysis using a series of mathematical conversions to make estimates of effect from a re-randomized controlled trial more comparable with those of a trial with parallel group design.

• After induction, golimumab was not statistically distinguishable from the other anti-TNFs. Treatment rankings, however, suggested golimumab may be superior to adalimumab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction.

• Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission.

• Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing.

• Golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing.

Notes