Inflammatory Bowel Disease Treatment Success Influenced by Serum Levels

Serum levels may determine impact of anti-tumor necrosis factor drugs.

The success of treatments for inflammatory bowel disease (IBD) may be directly influenced by the serum levels of anti-tumor necrosis factor (TNF) agents, recent research indicates.

A study published in Clinical Gastroenterology and Hepatology suggests a significant link between these serum levels and mucosal healing in patients with IBD.

As the use of anti-TNF agents in the treatment of IBD has grown, the success of this treatment has varied. Some patients respond well to anti-TNF agents, while a subgroup of IBD patients either fail to respond or lose response to these drugs.

Among patients who do respond, it has yet to be specifically determined what dosage of anti-TNF medications should be administered. Determining the optimal treatment level of anti-TNFs is vital because cytokine manipulation carries potentially harmful consequences.

For the current study, researchers evaluated data from colonoscopy examinations for 145 IBD patients in Israel between 2009 and 2014. As part of the retrospective cross-sectional study, patients were administered either infliximab (n=78) or adalimumab (n=67).

Mucosal healing was defined as simple endoscopic score of <3 or a Mayo score ≤1. The data was compared with serum levels of anti-TNF agents, clinical scores, and levels of c-reactive protein.

The results showed what was termed a therapeutic window with serum levels of 6—10 μg/ml for infliximab and 8–12 μg/ml for adalimumab.

Levels inside this window were necessary in order for patients with IBD to achieve mucosal healing of 80%—90%.

“Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing,” the researchers noted.

Infliximab levels above 5 μg/ml and levels of adalimumab above 7.1 μg/ml identified patients with mucosal healing of 85% specificity. The researchers found that increasing infliximab levels above 8 μg/ml caused only improvement in the rate of mucosal healing.

Conversely, the association between higher adalimumab levels and an increased rate of mucosal healing plateaued at 12 μg/ml.

Among patients with measurable levels of infliximab, the presence of antibodies to the drug was associated with a lower mucosal healing rate compared with patients at a similar drug level without antibodies (16% versus 50%, respectively, P=.003).

The researchers said they plan to further evaluate the optimum serum levels along with the potential long-term consequences from anti-TNF in the treatment of IBD.