Adalimumab therapy may reduce health-care costs for Crohn's disease patients

Nov 12 2008

Inflammatory bowel disease (IBD) is a term that refers to both ulcerative colitis (UC) and Crohn's disease (CD).

IBD occurs most frequently in people in their late teens and twenties. There have been cases in children as young as two years old and in older adults in their seventies and eighties; men and women have an equal chance of getting the disease.

While the cause(s) of IBD are not known, one theory is based on genetics, indicating that IBD runs in families. About 15 percent to 30 percent of patients with IBD have a relative with the disease. Research is underway to find out if a specific gene or a group of genes makes a person more susceptible to getting the disease. Additionally, many changes in the body's immune system have been discovered in patients with IBD. There is a large amount of research being done in this area as well, including studies to find out if IBD is caused by an infectious agent.

Two recent studies published in Gastroenterology and Clinical Gastroenterology and Hepatology further our understanding of these major illnesses.

Adalimumab Therapy May Provide Important Economic Benefits for Crohn's Disease Patients

Crohn's disease (CD) patients treated with adalimumab have lower one-year risks of hospitalization and surgery, reports a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

Adalimumab is an anti-tumor necrosis factor (TNF) monoclonal antibody, of human origin, effective for inducing and maintaining clinical response and remission in patients with moderate to severe CD. It is approved for the treatment of CD in North America and Europe.

All data used in these analyses were collected during the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM) trial, a multi-center, Phase III, double-blind, randomized, placebo-controlled study. This analysis was the first to examine the effect of adalimumab maintenance treatment on both all-cause and CD-related hospitalizations. Of the 778 patients randomized, 260 were assigned to adalimumab every other week, 257 were assigned to adalimumab weekly and 261 received placebo.

Both three- and 12-month hospitalization risks were significantly lower for patients who received adalimumab. In addition, adalimumab every other week and weekly maintenance therapies were associated with 52 percent and 60 percent relative reductions in 12-month, all-cause hospitalization risk, and 48 percent and 64 percent reductions in 12-month risk of CD-related hospitalization.

The combined adalimumab group was associated with 56 percent reductions in both all-cause and CD-related hospitalization risks. Fewer CD-related surgeries occurred in the adalimumab every other week, weekly and combined groups compared with placebo (0.4, 0.8 and 0.6 versus 3.8 per 100 patients, all p<0.05).

"It is important to recognize that CD patients experience comorbidities such as osteoporosis, depression and anxiety disorders, which may improve following successful medical management," said Brian G. Feagan, MD, of the University of Western Ontario and lead author of the study. "Accordingly, the significant decrease in all-cause hospitalization we observed following adalimumab maintenance treatment suggests that therapy may reduce total health-care costs incurred by CD patients. Decreasing the incidence of hospitalization and surgery may be the key to controlling the total health-care burden of CD."

CD is a chronic inflammatory bowel disease that primary affects the small intestine and colon. Because it frequently occurs earlier in life than many other chronic conditions, it imposes a substantial burden. There is remarkable consistency in the literature that hospitalization costs, including surgery, make up 56 percent to 63 percent of the total direct costs. In addition, other economic studies have emphasized that CD patients requiring hospitalization are responsible for the majority of costs. Patients suffering from CD experience pain in the abdomen, often in the lower right side, diarrhea, weight loss and occasional bleeding.

5-ASA's Chemopreventive Role: No Effect

In longstanding patients with ulcerative colitis (UC), study findings failed to show that the use of 5-aminosalicylic acid (5-ASA) demonstrated definitive chemopreventative activity. In addition, those with flat low-grade dysplasia (fLGD) have a higher rate of progression to advanced neoplasia than those with no dysplasia (NoD) or indefinite dysplasia (IND), reports a new study in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute.

"Some studies have suggested that 5-ASA can prevent the development of colorectal cancer (CRC) in UC patients, although none have determined where in the colitis-dysplasia-carcinoma sequence these agents might act," said Thomas A. Ullman, MD, of the Mount Sinai School of Medicine and lead author of the study. "This study not only enabled doctors to address where in this process compounds might exert a chemopreventive effect, but it also allowed them to account for changes in 5-ASA exposure over time, an underappreciated concept in chemopreventive literature."

Three groups of UC patients were identified from an institutional database: 311 NoD patients, 56 with IND and 26 with fLGD. The impact of 5-ASA exposure on the subsequent development of advanced neoplasia (high-grade dysplasia or CRC) was assessed using life-table methods. Of the NoD patients, 17 progressed to advanced neoplasia (seven to CRC). For the IND group, four patients progressed (two to CRC) and 10 fLGD patients progressed (three to CRC).

A proportional hazards analysis was performed on the NoD cohort coding 5-ASA as a time-changing covariate and assessing its impact in three ways: 1) comparing those with 5-ASA use at any time during surveillance to non-users; 2) comparing those whose average dose was > 2 grams/day to those with ¡Ü 2 grams/day; and 3) calculating the overall effect of 5-ASA use for each 1 gram increase in dose over the course of surveillance. Using this model, no statistically significant chemopreventative effect was demonstrated comparing non-users to any 5-ASA users. However, point estimates slightly favored chemoprevention in the NoD and IND groups.

While the possibility remains that 5-ASA plays a chemopreventative role for CRC in UC, a larger study group is needed to demonstrate such an effect in a statistically significant way, and further studies are required.

UC occurs only in the inner lining of the colon (large intestine) or rectum. Inflammation of the rectum and colon keeps water from being absorbed into the bloodstream and results in diarrhea, abdominal cramps and rectal bleeding. In addition, the risk of colon cancer is higher in UC patients with involvement of the entire colon and in patients who have had the diagnosis for eight to 10 years or more. Patients with a diagnosis of left-sided UC for 15 to 20 years also fall into a higher risk group for developing cancer.