Higher adalimumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease

Abstract

Background: The relationship between serum adalimumab concentrations and adverse events in patients with inflammatory bowel disease (IBD) is unknown. We aimed to determine whether patients with IBD using adalimumab are at increased risk of adverse events if they have higher adalimumab serum levels compared to those with lower adalimumab levels.

Methods: This was a retrospective study of 191 IBD patients with at least one serum adalimumab level measurement available. The cohort was divided using a cutoff level of 10 mcg/mL. The primary outcome was the rate of overall adverse events between the two groups. Secondary outcomes included rate of infections, dermatologic reactions, injection-site reactions and other adverse events in both groups. Rates of discontinuation of adalimumab due to adverse events were evaluated. Multivariate logistic regression analysis was performed to evaluate the relationship between adalimumab levels and adverse events.

Results: A total of 41 adverse events were reported in 191 patients in the overall cohort. Among 86 patients with higher adalimumab levels, 22 adverse events were reported, vs. 19 adverse events among 105 patients with lower adalimumab levels (25.6% vs. 18.1%, p = .21). Analysis according to adalimumab level tertiles also did not show significant differences in the rates of adverse events. A multivariate forward selection model also did not find higher odds of an adverse event in IBD patients with higher adalimumab levels compared to lower levels (OR 1.54, 95% CI 0.77–3.08).

Conclusions: There does not appear to be a relationship between adalimumab exposure and risk of adverse events in IBD patients.

Keywords:

• Adalimumab
• safety
• inflammatory bowel disease
• Crohn’s disease
• UC
• ulcerative colitis
• infections

Disclosure statement

Dr. Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Dr. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck and Ferring. John K. Marshall has received honoraria from Janssen, AbbVie, Aptalis, Astra-Zeneca, Ferring, Forest, Optimer, Procter & Gamble, Shire, Takeda and Warner-Chilcott. No other authors had any conflicts of interest to declare with regards to this manuscript.