Original article
Association of Trough Serum Infliximab to Clinical Outcome After Scheduled Maintenance Treatment for Crohn’s Disease

https://doi.org/10.1016/j.cgh.2006.06.025Get rights and content

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 μg/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.

Section snippets

Patients

A consecutive cohort of 105 patients with refractory inflammatory and/or perianal fistulizing Crohn’s disease who initiated infliximab treatment between March 2000–February 2005 were studied. At baseline, the induction protocol for fistulizing disease was infliximab 5 mg/kg infused intravenously at 0, 2, and 6 weeks, and for inflammatory disease it was either the 3-dose induction or a single infusion at 5 mg/kg. Thereafter, 82 patients received 5 mg/kg infliximab at regular scheduled intervals

Patients

Baseline characteristics of the 105 patients are shown in Table 1. The indication for infliximab was inflammatory disease in 66 patients and inflammatory disease associated with perianal fistulizing disease in 39 patients. Thirty-one patients received concurrent immunosuppressive therapy (azathioprine or methotrexate). After infliximab induction treatment, 82 patients received scheduled maintenance infliximab therapy at a maximum interval of 8 weeks, and 23 patients received episodic infliximab

Discussion

Infliximab is now an established treatment for patients with refractory Crohn’s disease.2, 4 However, Crohn’s disease is a chronic illness that frequently requires long-term treatment, and understanding why some patients derive less benefit with infliximab is an important focus for investigation. Our results showed for Crohn’s disease patients receiving maintenance infusions of infliximab treatment at scheduled intervals, the proportion of patients who obtained clinical benefit was similar for

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Supported by the Campacci Research Fund for Inflammatory Bowel Disease of the Mount Sinai Hospital.

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