In patients with moderate to severe ulcerative colitis, the safest, most effective agents may be infliximab, ustekinumab, and tofacitinib, according to study results published in Clinical Gastroenterology and Hepatology.

There is a significant knowledge gap and limited studies available on safe, effective first- and second-line treatments for the management of moderate to severe ulcerative colitis. The objective of this study was to compare the efficacy and safety of different first- and second-line agents including infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, and ustekinumab for the treatment of moderate to severe ulcerative colitis.

In this study, researchers searched publication databases for randomized trials of adults with moderate to severe ulcerative colitis who had been treated with first- or second-line agents including tumor necrosis factor antagonists, vedolizumab, tofacitinib, or ustekinumab. The outcomes of these treatments were compared with the outcomes of placebo or other active agents. Efficacy outcomes were the induction of clinical remission and endoscopic improvement. Safety outcomes were any adverse event, adverse events leading to discontinuation of drug therapy, serious adverse events, and serious infections.

Through results from direct meta-analysis, study researchers noted that all agents were superior to placebo at inducing clinical remission, with the effect size being strongest for infliximab and vedolizumab (odds ratio [OR], 4.07; 95% CI, 2.68-6.16 and OR, 3.10; 95% CI, 1.53-6.26, respectively). Infliximab and vedolizumab also demonstrated strong effect sizes for the induction of endoscopic improvement (OR, 3.32 and OR, 2.52, respectively).


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In patients who had previously been treated with tumor necrosis factor antagonists, ustekinumab and tofacitinib were ranked highest among second-line agents for inducing clinical remission, both with a surface under the cumulative ranking (SUCRA) of 0.87. The rate of serious active infection was lower with vedolizumab compared with tofacitinib (OR, 0.56; 95% CI, 0.32-0.98), and overall, vedolizumab and ustekinumab were ranked safest in terms of infection risk (SUCRA, 0.81 and SUCRA, 0.63, respectively).

The main limitation of this study was that researchers were unable to properly assess the validity of results from all trials included in the meta-analyses.

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The study researchers concluded that infliximab may be the safest, most effective first-line agent in moderate to severe ulcerative colitis and that ustekinumab and tofacitinib may be the safest, most effective second-line agents for patients who fail infliximab.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Singh S, Murad MH, Fumery M, Dulai PS, Sandborn WJ. First- and second-line pharmacotherapies for patients with moderate to severely active ulcerative colitis: an updated network meta-analysis [published online January 13, 2020]. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2020.01.008