A systematic review and meta-analysis of 17 randomized controlled trials examined how prior exposure to tumor necrosis factor (TNF) antagonists affects the efficacy of advanced therapies in ulcerative colitis.

The analysis included nearly 9,000 patients, almost half with prior TNF exposure. Lymphocyte trafficking inhibitors such as vedolizumab and S1P modulators were significantly more effective in TNF-naive patients, with efficacy reduced by about 50% after TNF use.

In contrast, interleukin antagonists showed consistent efficacy regardless of TNF history, though ustekinumab appeared more effective in TNF-exposed patients. JAK inhibitors demonstrated greater remission rates in TNF-exposed patients compared with TNF-naive patients, supporting their role as a post-TNF option. 

Mechanistic explanations include TNF-induced immune reprogramming, reduced leukocyte trafficking affecting trafficking inhibitors, and heightened IL-6/JAK/STAT signaling enhancing JAK inhibitor response.

These findings suggest treatment sequencing should be guided by prior biologic exposure, with trafficking inhibitors best suited for biologic-naive patients, JAK inhibitors prioritized after TNF failure, and IL antagonists broadly effective across both groups. 

Source: Clinical Gastroenterology and Hepatology