An Elevated Body Mass Index is Associated with Lower Serum Adalimumab Levels without Clinical Significance

Abstract

Background: Biologics, specifically anti-TNF agents, have been an integral part of our treatment paradigm for IBD for several years. However, therapeutic drug monitoring (TDM) enhances our ability to optimize dosing regimens. Studies have shown that trough levels<4.9ug/ mL are associated with loss of response to adalimumab (ADA). An increased body weight may change the pharmacokinetics of adalimumab in IBD. The primary aim of this study was to evaluate the impact of body mass index (BMI) on adalimumab drug levels in IBD patients, as well as its potential clinical implications. Methods: A database was compiled via retrospective chart review of 507 IBD patients seen at our Digestive Disease Center (DDC) between July 2013 and March 2016. Variables in the database include patient’s weight, medications, serum adalimumab levels, dates of medication administration, endoscopic findings, fecal calprotectin, erythrocyte sedimentation rate, and C-reactive protein. Results: Using ANOVA to compare the two groups, there was a significant association with lower ADA levels in patient with BMI >30kg/ m2 when compared to those with BMI <30kg/m2 (p = 0.009). Average adalimumab levels in these two groups were 11.8ug/mL and 8.8ug/mL, respectively. Within these groups, there was no statistically significant difference in severity of endoscopic findings. Furthermore, there was no statistically significant difference in serum inflammatory markers between groups. Conclusion: In a cohort of patients with inflammatory bowel disease, despite a downward trend in serum adalimumab levels as weight increased, there did not seem to be any apparent clinical significance to these findings. They neither correlated to severity of endoscopic findings, or to elevations in serum inflammatory markers. 57% of the total sample size was either overweight or obese, which we feel accurately reflects the phenotypic breakdown of the overall IBD population, as well as that of the general population. More studies are needed to follow the long-term progression of these lower adalimumab levels to determine if this leads to increased antidrug antibody formation and/or loss of response over time.