Efficacy of Biologics and Small Molecule Drugs for Moderate-to-Severe Ulcerative Colitis

Although the use of upadacitinib was superior for the induction of clinical remission when compared with other agents commonly used to treat moderate-to-severe ulcerative colitis (UC), the biologic ranked highest in the incidence of adverse events (AEs), according to a new study.

Researchers utilized articles published in online databases between Jan 1, 1990, and July 1, 2021, and manually reviewed major congresses' databases from Jan 1, 2018, to July 3, 2021. Only phase 3, placebo-controlled or head-to-head randomized controlled trials assessing the efficacy of these medications as induction or maintenance therapies were included. The primary objective was the induction of clinical remission.

A total of 29 studies were included. Of these, 23 studies evaluated induction therapy with either a biologic or small molecule drug, comprising 10,061 patients with UC. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission, including: 

  • infliximab (OR 2.70, 95% CI; 1·18 – 6·20)
  • adalimumab (4.64, 2.47 – 8.71)
  • golimumab (3.00, 1.32 – 6.82)
  • vedolizumab (3.56, 1.84 – 6.91)
  • ustekinumab (2.92, 1.31 – 6.51)
  • etrolizumab (4.91, 2·59–9·31)
  • tofacitinib (2.84, 1.28 – 6.31)
  • filgotinib 100 mg (6.15, 2.98 – 12.72)
  • filgotinib 200 mg (4.49, 2.18 – 9.24)
  • ozanimod (2.70, 1.18 – 6.20)

Upadacitinib also ranked highest for the induction of clinical remission. No differences between active interventions were detected when evaluating AEs and serious AEs. Vedolizumab ranked lowest for both AEs and serious AEs, upadacitinib ranked highest for AEs, and ozanimod ranked highest for serious AEs.

The authors concluded, “Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent with regard to adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes.” With the lack of direct comparisons in the published literature, the researchers noted that their results might help clinicians to position drugs in treatment algorithms.


—Yvette C. Terrie, BS Pharm, RPh


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.