BACKGROUND: Most patients who have active Crohn’s disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the eff ectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn’s disease who had not previously received glucocorticoids, antimetabolites, or infl iximab.
METHODS: We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infl iximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infl iximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infl iximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modifi ed intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710.
FINDINGS: Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60·0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35·9%) of 64 controls, for an absolute diff erence of 24·1% (95% CI 7·3–40·8, p=0·0062). Corresponding rates at week 52 were 40/65 (61·5%) and 27/64 (42·2%) (absolute diff erence 19·3%, 95% CI 2·4–36·3, p=0·0278). 20 of the 65 patients (30·8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25·3%) controls (p=1·0).
INTERPRETATION: Combined immunosuppression was more eff ective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn’s disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.