Higher Adalimumab Trough Level Not Linked to Increased Adverse Events in IBD Treatment

Samantha Ellison, MD

While previous studies on ant-TNF medications, such as adalimumab (ADA), have showed increased risk of infection in patients with inflammatory bowel disease (IBD), there is limited data on safety outcomes stratified by trough levels.

Investigators, led by Samantha Ellison, MD of the University of Pennsylvania, found that in the cohort of IBD patients, higher ADA trough concentration did not have an association with a higher likelihood of adverse events.

The study was presented online at the 2021 Digestive Disease Week (DDW) Virtual Meeting.

Study

Investigators conducted a retrospective cohort study of IBD patients followed at a tertiary IBD center, treated with ADA and had therapeutic drug monitoring (TDM) during their treatment between January 2010 – September 2020.

The team assessed included demographics, dose, prior anti-TNF exposure, concomitant immunomodulator and/or steroid use, ADA trough and antibody levels, adverse events, and vaccination status.

Further, the adverse events studied included infusion reactions, blood disorders, autoimmune disorders, dermatological disorders, and cardiac and neurological conditions.

Investigators included patients with at least a 3-month assessment both pre- and post-TDM. For patients with multiple ADA levels, the highest level was taken for analysis.

The team divided ADA levels into quartiles to assess for adverse event risk (<5.4, 5.5 - 11, 11.1 - 16.7 and >16.7 ug/mL).

Results

A total of 435 IBD patients were included in the study, with a median age of 38.4 years and 44.6% male patients.

In the cohort, 76.8% of patients had Crohn’s disease, 23.0% had ulcerative colitis (UC), and 0.2% had IBD-undetermined (IBD-U) or indeterminate colitis (IC).

The team noted that adverse events occurred in 28 (6.43%) patients, with the most common events including localized injection reactions (60%) and dermatologic disorders (20%).

After univariable analysis, it was found that ADA trough concentration was not associated with adverse events (41.1% versus 58.6%, P = .337).

Further, investigators noted concomitant steroid (100 versus 0%, P = .126), immunomodulator (82.8 versus 17.2%, P = .444), or narcotic use (100 versus 0%, P = .464) were not associated with an increased risk of adverse events.

However, Investigators noted after accounting for number of months on ADA treatment and number of prior biologics, females had an association with developing adverse events (aOR 4.2, 95% CI 1.57-11.25), in comparison to males.

Neither concomitant steroid (100 vs. 0%, p=0.126), immunomodulator (82.8 vs. 17.2%, p=0.444) or narcotic use (100 vs 0%, p=0.464) were associated increased risk of adverse events.

Conclusion

Investigators concluded that within the cohort of IBD patients, higher ADA trough concentration did not have an association with a higher likelihood of adverse events.

However, the team noted females were found to have higher odds ratios of developing adverse events.

“These results suggest it is reasonable to target higher drug levels without concern for additional adverse drug reactions,” investigators wrote.

The study, “Adalimumab Trough Concentration Is Not Associated with Adverse Events in Patients With IBD,” was presented online at DDW.