Higher concentrations of cytokine blockers are needed to obtain small bowel mucosal healing during maintenance therapy in Crohn's disease

Abstract

Several studies have reported a positive correlation between serum drug concentrations and endoscopic remission in patients with Crohn's disease. To examine the association between the concentrations of cytokine blockers (infliximab, adalimumab and ustekinumab) and endoscopic remission of small bowel lesions. This was a cross-sectional study conducted at a single tertiary referral centre. Patients with Crohn's disease who received maintenance cytokine blocker therapy were recruited from April 2018 to May 2020. We performed balloon-assisted enteroscopy and collected serum samples to measure drug concentrations. The primary endpoint was the relationship between the concentrations of cytokine blockers and endoscopic remission in the small bowel. We enrolled 143 patients, 66, 44 and 33 of whom were receiving infliximab, adalimumab and ustekinumab, respectively. Enteroscopic findings showed that the rate of endoscopic remission of small bowel lesions was significantly lower than that of colonic lesions (P<0.01). For each agent, the mean drug concentration in patients exhibiting endoscopic remission in the small bowel was higher than that observed in patients with endoscopic remission in the colon (but not in the small bowel) or with any active disease (either in the small bowel, colon or both). Patients with infliximab, adalimumab and ustekinumab concentrations >5, 14 and 4µg/mL were nearly 5.3-, 9.4- and 14.7-times more likely to exhibit endoscopic remission of the small bowel, respectively. Cytokine blocker treatment was less efficacious for small bowel inflammation than colonic inflammation. Higher serum concentrations were needed to achieve endoscopic remission of small bowel lesions.