Top Down Versus Step Up Strategies in Crohn's Disease

The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux

The study prospectively compares two treatment algorithms for newly diagnosed Crohn's disease: one 'aggressive' treatment with early introduction of immunomodulators and biologicals and one 'standard treatment' with corticosteroids and only later introduction of immunosuppressives and biologicals if disease activity requires that.

This two year open-label randomized trial compares the early use of combined immunosuppression to conventional management in patients with active Crohn's disease who have not previously received glucocorticoids, antimetabolites, or infliximab. Patients assigned to combined immunosuppression receive azathioprine and 3 infusions of 5 milligrams per kilogram of body weight of infliximab at weeks 0, 2, and 6. Retreatment with infliximab and, if ultimately necessary, corticosteroids are used to control disease activity. Patients assigned to conventional management receive corticosteroids followed, in sequence, by azathioprine and infliximab. The primary outcome measure is remission without corticosteroids and without bowel resection at weeks 26 and 52.

Inclusion Criteria:

• age 16 - 75 years
• diagnosis of Crohn's disease within the past 4 years
• no previous treatment with corticosteroids, antimetabolites, or biologic agents.
• Active Crohn's disease, defined by a Crohn's Disease Activity Index (CDAI)20 score of greater than 200 points for a minimum of 2 weeks prior to randomization.

Exclusion Criteria:

• immediate need for surgery
• symptomatic stenosis or ileal/colonic strictures with prestenotic dilatation;
• signs, symptoms or laboratory tests indicating severe, medical disease;
• documented chronic infection
• a positive stool culture for pathogens
• a positive tuberculin test or a chest radiograph consistent with tuberculosis.
• malignancy
• allergy to murine proteins
• pregnancy
• substance abuse