The choice of biologics and oral small molecule drugs for treatment of ulcerative colitis may be informed by the latest results indirect comparisons, the authors of a new review say.

In the absence of head to head trials for many agents, decisions on the selection and positioning of therapy may be helped by findings from an updated systematic review and network meta-analysis, they write in Lancet Gastroenterology and Hepatology

The review evaluated data on induction therapy with either a biologic or small molecule drug from 23 studies involving over 10,000 patients with moderate-to-severe ulcerative colitis.

Based on clinical remission and endoscopic improvement endpoints the review authors found that 45 mg/day of upadacitinib was the best performing agent compared to other interventions, while infliximab ranked second for both outcomes.

Upadacitinib was found to be superior for the induction of clinical remission compared to infliximab [OR 2·70], adalimumab [4·64], golimumab [3·00], vedolizumab [3·56], ustekinumab [2·92], etrolizumab [4·91], tofacitinib [2·84], filgotinib 100 mg [6·15], filgotinib 200 mg [4·49], and ozanimod (2·70). It also ranked highest for the induction of clinical remission (SUCRA 0·996).

However, upadacitinib also ranked highest for adverse events, with a score of 0·843 by surface under the cumulative ranking (SUCRA), while ozanimod ranked highest for serious adverse events (SUCRA 0·831). Vedolizumab was ranked as the safest drug in terms of adverse events and serious adverse events,

Tofactinib and infliximab were ranked highest for the maintenance of steroid-free remission in randomised responders and treat-straight-through studies, respectively.

The study authors said that until the findings of head-to-head comparison studies become available, the results for relative efficacy and safety of the currently available treatment options might help inform patterns of use and drug positioning in ulcerative colitis.

However they acknowledged that the findings had limitations because indirect comparisons made it difficult to account for biologic-naive and biologic-exposed patients, disease phenotypes, and different endpoint definitions.

“As with any indirect comparison, the 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,” they wrote.

An accompanying commentary said the review had shown that small molecule drugs are poised to transform ulcerative colitis care, but it is unlikely that a single, definitive, first-line agent of choice for moderate-to-severe ulcerative colitis will emerge, “nor will there be a one-size-fits-all therapeutic sequence.”

“Different approaches to using small molecule drugs should be considered, including potentially as corticosteroid-sparing agents, as rescue treatment for patients with acute severe ulcerative colitis, as preferred agents for patients with systemic extraintestinal manifestations, or as part of a combination regimen for patients with high-risk disease,” the authors suggested.