TNF-α antagonists superior to vedolizumab, ustekinumab for endoscopic healing in CD

The tumour necrosis factor-alpha (TNF-α) antagonist therapies adalimumab and infliximab are more effective than vedolizumab and ustekinumab in achieving endoscopic healing (EH) at 1 year among patients with moderate-to-severe Crohn’s disease (CD), a recent study has shown.

“The evolving importance for EH and the known disconnect between symptoms and objective measures of disease activity make the superiority of TNF-α antagonist therapies for EH important when considering which agents should be used first-line in routine practice,” said the researchers.

“Safety, convenience, and cost of therapy also influence decision making, and the availability of biosimilar TNF-α antagonist therapies in routine practice adds additional consideration for cost-effectiveness in population health decisions,” they added.

Lead researcher Dr Neeraj Narula from the Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton ON, Canada, and colleagues compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab in a pooled analysis of data from 299 CD patients from four clinical trials.

The number of patients treated with each biologic were assessed for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). The researchers used multivariate logistic regression to explore the association between biologics and 1-year outcomes, adjusting for disease duration, concomitant corticosteroid use, and prior anti-TNF failure.

The TNF-α antagonists adalimumab (17/61, 27.9 percent; adjusted odds ratio [aOR], 5.79, 95 percent confidence interval [CI], 1.77‒18.95; p=0.004) and infliximab (39/141, 27.7 percent; aOR, 4.59, 95 percent CI, 1.48‒14.22; p=0.008) delivered superior rates of 1-year EH when compared with vedolizumab (4/56, 7.1 percent). [Am J Gastroenterol 2022;117:1106-1117]

Vedolizumab showed no significant difference from ustekinumab. Results seen among biologic-naïve patients were similar.

In patients with baseline ileal SES-CD ≥3, differences between biologics for 1-year ileal EH were also not significant. However, infliximab (20/49, 40.8 percent) was superior to vedolizumab (2/23, 8.7 percent; aOR, 5.39, 95 percent CI, 1.03‒28.05; p=0.045) for large (>0.5 cm) ileal ulcers. No other differences had been observed.

For colonic disease, adalimumab (30/48, 62.5 percent; aOR, 3.97, 95 percent CI, 1.45‒10.90; p=0.007) showed better rates of 1-year EH in the colon than ustekinumab, with similar trends noted for infliximab (55/105, 52.4 percent; aOR, 2.08, 95 percent CI, 0.82‒5.27; p=0.121). No other differences were seen.

More difficult to heal

“It has previously been suggested that the ileum does not heal as well as the colon, both with anti-TNF-α biologics and other advanced therapies,” the researchers said. [Gastroenterology 2019;157:1007-18.e7; J Crohns Colitis 2017;11:425-434; Gastroenterology 2018;154:S24]

“Given the relative difficulty of achieving healing in the small bowel/ileum, future studies should consider separating results of patients with only small bowel/ileal disease to better inform positioning of therapies,” they added.

It remains unclear why the ileum or small bowel is more difficult to heal, but it is thought that differences in immune tolerance and microbiome profiles account for differences in healing of the ileum as compared with the colon. [Gut 2016;65:256-270]

“Further randomized controlled trials comparing biologic therapies in CD are warranted to confirm or refute the findings of this study,” the researchers said.