Results from a systematic review and meta-analysis published in the Lancet Gastroenterology & Hepatology describe the relative efficacies of certain biologics and small molecule drugs for the treatment of moderate to severe ulcerative colitis (UC). Upadacitinib emerged as the best-performing agent for the induction of clinical remission but had the highest rate of adverse events. Vedolizumab, by contrast, had the fewest safety events but appeared less effective for achieving remission.

Investigators searched MEDLINE, Embase, and the Cochrane Register of Controlled Trials for articles published between 1990 and 2021. Eligible trials had a randomized design and described the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for moderate to severe UC. The primary outcome of interest was the induction of clinical remission.

A network meta-analysis was conducted to obtain pairwise odds ratios (ORs) for the likelihood of clinical remission with each agent. The surface under the cumulative ranking (SUCRA) was used to rank treatment agents by outcome; higher SUCRA scores indicated better efficacy, while lower SUCRA scores indicated better safety.


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The initial search yielded 5094 results, from which 29 studies were included. Twenty-three of these studies assessed induction therapy with either a biologic or small molecule drug and had a pooled cohort of 10,061 patients.

Upadacitinib ranked highest for the induction of clinical remission (SUCRA, 0.996) and outperformed all other active interventions. Specifically, patients taking upadacitinib had a greater likelihood of clinical remission compared with patients taking infliximab (OR, 2.70; 95% CI, 1.18-6.20), adalimumab (OR, 4.64; 95% CI, 2.47-8.71), golimumab (OR, 3.00; 95% CI, 1.32-6.82), vedolizumab (OR, 3.56; 95% CI, 1.84-6.91), ustekinumab (OR, 2.92; 95% CI, 1.31-6.51], etrolizumab (OR, 4.91; 95% CI, 2.59-9.31), tofacitinib (OR, 2.84; 95% CI, 1.28-6.31), filgotinib 100 mg (OR, 6.15; 95% CI, 2.98-12.72), filgotinib 200 mg (OR, 4.49; 95% CI, 2.18-9.24), or ozanimod (OR, 2.70; 95% CI, 1.18-6.20).

Vedolizumab ranked lowest for adverse events (SUCRA, 0.184) and serious adverse events (SUCRA, 0.139), suggesting a safety benefit with this drug. Upadacitinib ranked highest for adverse events (SUCRA, 0.843) and ozanimod ranked highest for serious adverse events (SUCRA, 0.831). All active interventions were superior to placebo for maintaining clinical remission. Vedolizumab (SUCRA, 0.906) and subcutaneous infliximab (SUCRA, 0.716) ranked highest for the maintenance of clinical remission.

Investigators noted study limitations, including definitions of clinical remission that varied somewhat between trials, creating heterogeneity in results.

This meta-analysis compared the efficacy and safety of several biologics and small molecule drugs for the treatment of UC. Overall, upadacitinib outperformed other agents for the induction of clinical remission, but was associated with higher risk for safety events. Vedolizumab was associated with the lowest risk for adverse events.

“[T]he results presented in this study should be interpreted with caution but could help clinicians to navigate the current scenario in which the number of therapeutic options for moderate-to-severe ulcerative colitis is steadily increasing,” investigators wrote. “These findings should be interpreted as hypothesis-generating, until direct comparisons by means of head-to-head trials become available to fully elucidate the positioning of these therapies.”

Disclosure: The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Lasa JS, Olivera PA, Danese S, Peyrin-Biroulet L. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(2):161-170. doi: 10.1016/S2468-1253(21)00377-0