Background & aims: The effect of infliximab infused at scheduled intervals on antibody formation, preinfusion trough serum concentrations of infliximab, and their clinical significance was evaluated in patients with Crohn's disease.
Methods: Antibodies to infliximab and trough serum infliximab were measured in 105 patients with Crohn's disease treated with 5 mg/kg infliximab for induction followed by maintenance episodic re-treatment (n = 23) or scheduled therapy at 6- to 8-week intervals (n = 82).
Results: After a median of 14 infusions (range, 2-45), 21% of patients had detectable antibodies, 25% were antibody negative, and 54% were antibody inconclusive. Antibody formation was higher after episodic compared with scheduled treatment (39% vs 16%; P = .036) and was associated with a higher rate of infusion reactions (50% vs 21%; P = .018). Ninety patients continued maintenance scheduled therapy beyond 12 months including 12 converted episodic patients, with a median follow-up of 23 months (range, 16-68 months). The rate of clinical remission was higher for patients with a detectable trough serum infliximab compared with patients in whom serum infliximab was undetectable, including those without antibodies (82% vs 6%; P < .001). A detectable trough serum infliximab was also associated with a lower C-reactive protein (2.0 vs 11.8 mug/L; P < .001) and a higher rate of endoscopic improvement (88% vs 33%; P < .001). Concurrent immunomodulators did not alter outcomes.
Conclusions: For Crohn's disease patients treated with scheduled maintenance infusions of infliximab, the trough serum concentration of infliximab predicts clinical outcome. Factors in addition to antibody formation, likely pharmacokinetic, modulate serum infliximab and thus the response to infliximab therapy.