Higher adalimumab levels tied to Crohn's disease remission

Last Updated: 2018-11-07

By David Douglas

NEW YORK (Reuters Health) - In patients with Crohn's disease on maintenance therapy with adalimumab, higher levels of the anti-TNF agent are associated with biologic remission, according to Scottish researchers.

Regular endoscopic assessment to guide treatment is both invasive and costly, and therapeutic-drug monitoring is being increasingly adopted, Dr. Nikolas Plevris and colleagues at Western General Hospital in Edinburgh note in Inflammatory Bowel Diseases, online October 17. However, limited data are available on the relationship between adalimumab drug levels and serum and fecal markers of gut inflammation, they add.

To gain further information, the researchers prospectively studied 152 patients who had received adalimumab therapy for a minimum of 12 weeks after standard induction treatment. Almost half received adalimumab as first-line biological therapy; the median therapy duration was two years.

Overall, median serum adalimumab level was 10.0 ug/mL and there was no significant difference in levels in patients with first-line exposure compared with those with previous biologic exposure. Biologic remission was defined as C-reactive protein (CRP) levels below 5 mg/L and fecal calprotectin below 250 ug/g.

Seventy-three patients (48.0%) were in biologic remission and their adalimumab levels (12 ug/mL) were significantly higher than in those who weren't in remission (8 ug/mL). In addition, increasing adalimumab-level quartiles were associated with significantly higher rates of biologic remission, with no plateau being reached.

Similar associations were seen between adalimumab-level quartiles and clinical activity as measured by the Harvey-Bradshaw Index as well as CRP levels and those of fecal calprotectin.

The team established that the optimal adalimumab level for predicting biologic remission was greater than 8.5 ug/mL. This had a sensitivity of 82.2%, a specificity of 55.7% and a likelihood ratio of 1.9.

Multivariable logistic regression analysis showed that adalimumab levels beyond 8.5 ug/mL were independently associated with biologic remission (odds ratio, 5.27).

The researchers caution, "Analysis is based on a single time point during maintenance therapy, and drug levels were not measured sequentially throughout the treatment schedule." It was also not possible to obtain endoscopic data at the time of therapeutic-drug monitoring, they add.

The team calls for further longitudinal studies to validate their findings, but concludes that the "approach is clinically practical and can be extrapolated to real-world practice."

Dr. Adam Cheifetz, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center, in Boston, told Reuters Health by email that this is "a very well-done association study that showed that higher adalimumab concentrations are associated with more objective outcomes, in this case biologic remission."

"This and other studies," concluded Dr. Cheifetz, who was not involved in the new research, "continue to demonstrate that higher drug concentrations (>8.5ug/ml) may be needed to attain better outcomes."

Dr. Jean-Frederic Colombel of Icahn School of Medicine at Mount Sinai, in New York City, appears less convinced.

"This is another one of multiple retrospective studies showing correlation and not causation between biologic drug levels and outcomes," he told Reuters Health by email.

Dr. Colombel, who has conducted research in the field but was not involved in the new study, added that it "still does not answer the critical question regarding usefulness of therapeutic-drug monitoring and whether it should be 'reactive' in patients losing response or 'proactive.'"

"So far," he said, "prospective studies have been negative and unable to show that treating to drug levels was associated with better outcomes than treating to symptoms (TAXIT and TAYLORIX studies)."

This, he noted, is why the American Gastroenterological Association has not as yet endorsed proactive therapeutic-drug monitoring.

Dr. Plevris did not respond to requests for comments.

SOURCE: https://bit.ly/2REvPxK

Inflamm Bowel Dis 2018.