Background: The anti-TNF antibodies Infliximab (IFX)and Adalimumab (Ada)are frequently used as maintenance therapy in Paediatric Inflammatory Bowel Disease (pIBD). However, the role and frequency of monitoring trough levels and anti-drug antibodies (ADA) during maintenance treatment remains unclear in children, with two regimens being considered, reactive vs. proactive approaches. Our aim was to investigate the trough levels of IFX and Ada, presence of ADA and identify correlation with inflammatory activity and clinical response.
Methods: Retrospective study of IBD patients on biologics (n=67, Crohn's disease [CD] (n=47), ulcerative colitis [UC] (n=11), inflammatory bowel disease unclassified [IBDU] (n=7), early onset IBD [EOIBD] (n=2); male (n=43), age range 4 years 3 months–17 years; median 13 years 8 months). Biologic monitoring was started in 2013. Demographics, CRP/ESR/albumin and activity indices PUCAI/PCDAI were recorded. Ada was started after Infliximab was discontinued (various reasons). All patients were on concomitant immunosuppressive treatment. 42 patients were on IFX only, 25 on Ada and 6 on Vedolizumab. 8 excluded due to insufficient data. Maintenance TNF treatment was 3–66 months, median 18 months.
Results: Group 1 Infliximab converted to Adalimumab; n=25 patients, n=7 excluded as no data available (pre through level availability); CD n=15, UC n=3, IBDU n=5, EOIBD n=2. The lowest Ada trough levels in n=15 showed a median of 5.6, range 0.3–17; the highest a median of 9.1, range 3.7–12.7. ADA for Ada was negative in 16 patients, n=5 became positive over time, n=2 were positive at first measurement.
Group 2 Infliximab only; n=42; the lowest IFX through levels had a median of 1.4, range <0.8–32.5, with highest through levels median 5.2, range 0–45. ADA for IFX were negative in n=37, n=7 developed antibodies over time, median ADA of 61, range 10–>200. 50% (21/42) of patients with either low through levels and/or positive ADA received double doses to salvage treatment. Overall there was clinical improvement; this did not though correlate with a reduction of ADA. However in 81% (17/21) of patients, double dosing led to an incremented of through levels above >2, median 4.1, range 2.4–21.9. Although only 15/67 (22%) out of 67 patients had completely normal laboratory tests, 42/47 (89%) CD patients had normal PCDAIs, 10/11 (91%)UC patients had normal PUCAIs. 14/47 (30%)CD patients developed antibodies to IFX, 2/11 (18%)UC patients developed antibodies to IFX.
Conclusions: The vast majority of patients on Adalimumab or Infliximab had an excellent clinical response to treatment regarding therapeutic drug monitoring, thus enabling us to optimize their treatment and bring them into clinical remission. We therefore advocate proactive biologic drug monitoring in Paediatric IBD.