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One Janus kinase (JAK) inhibitor was significantly superior to all other agents for inducing clinical remission in patients with moderate-to-severe ulcerative colitis (UC), but also ranked highest for adverse events, a network meta-analysis suggested.

In a comparative analysis of 29 studies, upadacitinib (Rinvoq) was significantly superior for inducing clinical remission and endoscopic improvement compared to all other examined agents, reported Juan S. Lasa, MD, of the Center for Medical Education and Clinical Research in Buenos Aires, Argentina, and colleagues.

However, upadacitinib also ranked highest for adverse events, while the monoclonal antibody vedolizumab (Entyvio) ranked lowest for both adverse events and serious adverse events, the authors wrote in .

Their study is the first to investigate safety and efficacy of an array of novel UC agents, including small molecule drugs.

Recent drug development in UC has shifted from anti-tumor necrosis factor (TNF) biologics toward small molecule drugs, such as the sphingosine-1-phosphate receptor agonist ozanimod (Zeposia), to overcome limitations of anti-TNF biologics such as adalimumab (Humira) or infliximab (Remicade), the group explained.

"As the number of therapeutic options for ulcerative colitis grows, clinicians and patients are faced with increasingly difficult decisions regarding which treatment to use and how therapies should be sequenced," Christopher Ma, MD, and May Y. Choi, MD, both of the University of Calgary in Canada, stated in an .

Lasa and colleagues evaluated data on 10,061 UC patients from 29 randomized controlled trials (RCTs) published from January 1990 to July 2021. They included four "head-to-head" RCTs as well as placebo-controlled phase III studies investigating the safety and efficacy of biologics and small molecule drugs for treating moderate-to-severe UC (defined as Mayo scores of 6 to 12) in adults. Induction of clinical remission was the primary outcome.

The analysis included trials involving FDA-approved agents for UC as well as unapproved agents. Most trials (23 of 29) tested induction therapy with infliximab, etrolizumab, adalimumab, vedolizumab, tofacitinib (Xeljanz), upadacitinib, ustekinumab (Stelara), filgotinib, ozanimod, and golimumab (Simponi).

Upadacitinib was significantly superior versus other agents in terms of inducing clinical remission:

• filgotinib 100 mg (OR 6.15, 95% CI 2.98-12.72)
• etrolizumab (OR 4.91, 95% CI 2.59-9.31)
• adalimumab (OR 4.64, 95% CI 2.47-8.71)
• filgotinib 200 mg (OR 4.49, 95% CI 2.18-9.24)
• vedolizumab (OR 3.56, 95% CI 1.84-6.91)
• golimumab (OR 3.00, 95% CI 1.32-6.82)
• ustekinumab (OR 2.92, 95% CI 1.31-6.51)
• tofacitinib (OR 2.84, 95% CI 1.28-6.31)
• infliximab (OR 2.70, 95% CI 1.18-6.20)
• ozanimod (OR 2.70, 95% CI 1.18-6.20)

Surface under the cumulative ranking (SUCRA) -- where higher scores demonstrate superior efficacy and lower scores demonstrate superior safety -- was used for ranking. Here, upadacitinib ranked highest for inducing clinical remission (SUCRA 0.996) and endoscopic improvement (SUCRA 0.999). In terms of safety, however, upadacitinib (SUCRA 0.843) ranked highest for adverse events, and ozanimod ranked highest for serious adverse events (SUCRA 0.831), while vedolizumab ranked lowest for both adverse events (SUCRA 0.184) and serious adverse events (SUCRA 0.139).

"Results from indirect treatment comparisons should be interpreted cautiously," the editorialists noted. "Study populations recruited into different trials are heterogeneous, particularly with respect to previous treatment failure, which is an important confounder of therapeutic efficacy."

The analysis had several other limitations, the researchers acknowledged, including that some data came from conference abstracts where full datasets remained unavailable.

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