Optimizing Crohn's Treatment: Hit It Hard or Be Conservative?

Crohn's disease is a chronic recurrent condition that is characterized by abdominal pain, diarrhea, and weight loss in more severe cases. The disease is thought to be mediated by uncontrolled inflammation in the digestive tract. The inflammation is hypothesized to be due to inefficient clearance of bacteria and food components that ultimately stimulate the immune system. Consequentially, this promotes damage to the digestive tract and the symptomatic manifestation of the disease. Although Crohn's can affect any portion of the digestive tract, from mouth to anus, the portion of the small intestine that dumps into the large intestine known as the illeocecal region is the most commonly afflicted area.

Therapy for Crohn's disease is centered on controlling inflammation and several medication classes are available, each with a specific place in the course of disease severity. A new randomized and double-blinded clinical trial published the New England Journal of Medicine assessed whether treating Crohn's more aggressively initially is more beneficial than the standard therapeutic approach.

Patients with moderate to severe crohn's for at least 6 weeks, had never used an immunomodulator drug, and were at least 21 years of age were included in the study. 508 patients were randomized based upon demographic information, Crohn's severity and location, along with previous treatments, into three treatment groups. Patients received azathioprine alone, infliximab alone, or a combination of the two.

The primary endpoint was corticosteroid free remission at week 26. Major secondary endopoints included corticosteroid free remission after week 26 and mucosal healing in patients who had ulceration at baseline. Patients who completed the study up to week 30 were given the option to extend treatment up to week 50. Infliximab is an anti-TNF agent reserved for patients that fail azathioprine therapy according to current treatment guidelines.

The authors observed that combination therapy induced remission at week 26 to the greatest statistical extent. Azathioprine induced remission in 30% of patients, infliximab in 44%, and the combination remission rate was 56.8%. Combination therapy (43.9%) was also more statistically effective than azathioprine alone (16.5%), but not infliximab alone (30.1%) in mucosal healing. A larger clinical trial using mucosal healing as a primary endpoint is needed to assess whether combination therapy is superior to infliximab alone.

Patients who stayed in the extend portion of the trial and received combination therapy were more likely to maintain clinical remission through week 50 than the other two groups. This suggests combination therapy may be better for both initiating remission and maintaining it. Adverse events were similar between the three groups, although one patient on combination therapy developed tuberculosis, a black box warning for infliximab treatment.

The trial suggests that combination therapy may be beneficial in treating Crohn's disease to both induce remission and maintain it. Doing so would ultimately help keep health care costs down by preventing surgeries and hospitalizations. However, a cost-benefit analysis would need to be done to verify this assertion. Likewise, longer term trials are needed to determine if combination therapy poses a significant health risk in comparison to the standard therapy in relation to adverse events.

References:

Colombel JF, et, al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95.