Clinical Use of Infliximab Trough Levels and Antibodies to Infliximab in Pediatric Patients With Inflammatory Bowel Disease.

Abstract

Optimizing infliximab (IFX) treatment in pediatric patients with inflammatory bowel disease (IBD) by using serum infliximab (S-IFX) trough levels and antibodies to IFX is recommended. There is need for studies assessing this strategy in clinical practice. We retrospectively identified all pediatric patients with IBD (n = 146, median age 14.8 years) treated with IFX at our tertiary referral center from 2003 to 2014. All were analyzed for IFX trough levels (S-IFX, n = 475), and IFX antibody (IFX-Ab, n = 219) titers were included. Both were analyzed using enzyme-linked immunosorbent assay. We correlated these parameters with concurrently analyzed fecal calprotectin levels and the treatment outcome. If IFX had no efficacy, or a loss of response occurred, 40 of 64 (63%) had trough levels <2.0 mg/L, with negative IFX-Ab in 37 of 59 (63%). If the S-IFX was very low (<0.2 mg/L), 4 of 36 still had negative IFX-Ab. Concurrent azathioprine therapy did not relate to IFX-Ab. Fecal calprotectin was significantly lower in patients with clinical remission or ongoing therapy compared with those with subsequent loss of efficacy: medians 95 μg/g (33-308) and 670 μg/g (264-1473), P < 0.0001. The S-IFX median was substantially higher in patients with either remission or ongoing therapy, compared with those with no or loss of efficacy: 3.7 mg/L (1.8-5.4) and 1.2 mg/L (0.03-4.4, P = 0.01), respectively. Measuring IFX trough levels and fecal calprotectin has a potential impact on the treatment strategies and should be included in clinical routine. Low IFX trough levels associate with increased antibodies to IFX in most, but not in all cases.