ACG: Weight Gain with Infliximab in Crohn's Disease Confirmed but Not Explained

PHILADELPHIA, Oct. 15 -- Unexplained weight gain in patients with Crohn's disease who are treated with infliximab remains a mystery, according to investigators in a small study reported here.

Patients gained as much as 60 to 75 pounds, far more than any weight gain observed in rheumatoid arthritis patients treated with infliximab, Cristal Brown a clinical research fellow at the University of North Carolina at Chapel Hill told attendees at the American College of Gastroenterology meeting.

"We're trying to cure the disease and a lot of these patients are malnourished," said Brown. "The question is, are we going to push them into being obese and having diseases and health risks that are associated with obesity?"

Crohn's disease is one of several conditions in which tumor necrosis factor-? may contribute to pathogenesis. Two effects of TNF-? are anorexia and cachexia. Thus, blocking the cytokine, which is targeted by infliximab, could affect body weight, said Brown.

One small prospective clinical study demonstrated significant weight gain accompanied by increased serum leptin levels in Crohn's disease patients after four weeks of infliximab therapy (J Clin Endocrinol Metab 2005; 90:3510-3516).

To continue the exploration, Brown and co-investigator Kim Isaacs, M.D., Ph.D. retrospectively reviewed records on 92 Crohn's patients and 51 rheumatoid arthritis patients who were at least 18 years of age and had received three or more infusions of infliximab. The Crohn's group comprised patients treated for luminal (N=58) or fistulous disease (N=34). Disease activity was assessed by the Harvey-Bradshaw Index before and after infliximab infusion.

Overall, the patients with Crohn's disease gained almost five times as much weight as the arthritis patients (4.97 kg versus 1.1 kg, P=0.0049). Some Crohn's patients gained as much as 20 to 30 kg, Brown reported.

Weight gain did not differ between patients with luminal versus fistulous disease or by steroid use, baseline body mass index, smoking status, or disease activity.

"There is a need for a larger prospective study to determine the cause of this weight gain and the role of leptin in the weight gain," said Brown. "The absence of significant weight gain in RA patients might provide some clues to the mechanism of action behind this effect."

Many Crohn's patients might benefit from modest weight gain because the disease has left them undernourished, Brown added. However, some patients clearly had excessive weight gain that poses a health hazard. Whether other anti-TNF therapies influence body weight has not been carefully examined, she said.