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Trough Infliximab Level Predicts Clinical Outcome in Acute Ulcerative Colitis

Gut 2010;59:49-54.

Trough serum infliximab levels predict clinical outcomes in patients with acute ulcerative colitis, investigators from Canada report in the January 2010 issue of Gut.

"For patients with ulcerative colitis or Crohn's disease who require anti-TNF therapy, optimizing treatment by the measurement of trough serum drug levels will improve clinical outcome and should become standard of care," Dr. Gordon Greenberg, from Mount Sinai Hospital in Toronto, told Reuters Health by email.

Dr. Greenberg and colleagues studied the relationship between trough serum concentrations of infliximab and antibody formation on clinical outcomes in 115 patients with moderately severe to severe ulcerative colitis. All patients received three-dose induction followed by scheduled maintenance infliximab. None had responded to steroids.

Sixty-eight patients (59%) had a clinical response and 37 (32%) achieved a clinical remission at week 10, the authors report.

By week 54, 43 patients (37%) were in steroid-free clinical remission.

During induction and maintenance, results were better for patients with moderately severe ulcerative colitis than for those with severe disease.

Most patients (66/108, 61%) had undetectable trough serum concentrations of infliximab, including 44 (41%) who were antibody positive and 22 (20%) who were antibody negative.

Compared to patients with undetectable trough concentrations, patients with detectable infliximab had higher rates of clinical remission (69% versus 15%), endoscopic improvement (76% versus 28%), endoscopic remission (27% versus 8%), and a lower rate of colectomy (7% versus 55%).

On multivariate analysis, a detectable trough serum concentration of infliximab was a significant positive predictor for clinical remission (odds ratio, 12.5) and endoscopic improvement (OR, 7.3), whereas an undetectable trough serum infliximab concentration was a significant positive predictor for colectomy (OR, 9.3).

A baseline Mayo score below 10 was also associated with remission (OR, 3.1), and baseline Mayo scores of 10 and above were associated with an increased risk for colectomy (OR, 3.3).

"The trough serum infliximab level appears to be a more useful predictor of clinical outcome than the presence of antibodies to infliximab, as it also takes into account the variable elimination of infliximab from the circulation," the investigators say.

They conclude that the high proportion of ulcerative colitis patients with undetectable serum trough infliximab suggests "that evaluation of higher induction dosing at shorter infusion intervals, particularly for severe ulcerative colitis, may be warranted."

Dr. Greenberg added, "Our results suggest that for patients with acute severe ulcerative colitis, an induction protocol of 5 mg/kg infliximab at 0, 2, 6 weeks may not be the optimal regimen. We are currently evaluating the effects of a higher dose, shorter interval induction regimen on serum trough infliximab levels and clinical outcome."

"Although our current study was undertaken in ulcerative colitis patients, we have previously shown that measurement of trough serum drug levels also predicts outcome in Crohn's disease," Dr. Greenberg continued. "Our studies were performed in infliximab-treated patients, but the concept of optimizing treatment by the measurement of trough serum drug levels applies to all therapeutic monoclonal antibodies employed in inflammatory bowel disease patients and likely would also be useful in other disease states (such as rheumatoid arthritis) as well."