Proactive Versus Reactive Monitoring of Anti-TNF Drug Levels: A Randomized Controlled Trial
Kenneth R. McQuaid, MD, FASGE reviewing Assa A, et al. Gastroenterology 2019 Oct.
In IBD, loss of response to anti-TNF therapy is more likely with low drug trough concentrations (TC) or positive antibodies (ADA). Measurement of TC and ADA is recommended in patients with suboptimal disease control to guide management (therapeutic drug monitoring [TDM]). However, the utility of proactive monitoring to guide dosing is uncertain – especially in patients in clinical remission. The authors conducted a multicenter trial in which biologic-naïve children with uncomplicated Crohn’s disease and clinical response to adalimumab induction at week 4 were randomized to proactive versus reactive drug monitoring. Patients were evaluated every 8 weeks for 72 weeks. At each visit, clinical activity, C-reactive protein (CRP), fecal calprotectin, TC, and ADA were measured. In the proactive group, drug dosing was increased, irrespective of clinical symptoms, for adalimumab levels <5 µg/ml. In the reactive group, physicians were informed of TC and ADA only in patients who were not in clinical and biologic remission.
A composite endpoint of sustained corticosteroid-free remission and biologic remission (CRP <0.5 mg/dl and fecal calprotectin <150 µg/g) for 72 weeks was reached by 42% (16/38) of children with proactive TDM versus 12% (5/40) with reactive TDM. In the proactive group, 55% of adalimumab dose increases were for low trough concentrations alone. There was no difference in clinical relapse between patients who did or did not receive immunomodulators at enrollment (44% of all patients). Drug antibodies occurred in 4 patients in each group, all of whom had adalimumab trough levels <3 µg/ml.
Comment:
This well-designed randomized controlled trial is the first to convincingly demonstrate that adjustment of adalimumab dosing based on proactive versus reactive monitoring results in higher sustained clinical and biological remission. To promote endoscopic remission, more recent studies support targeting even higher adalimumab trough levels (>7.5-10 µg/ml) than those assessed in this study.
Kenneth R. McQuaid, MD, FASGE
Citation(s):
Assa A, Matar M, Turner D, et al. Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn’s disease compared with reactive monitoring. Gastroenterology 2019;157:985-996.e2. (https://doi.org/10.1053/j.gastro.2019.06.003)
