In this study, researchers from France assessed whether infliximab, combined with azathioprine (AZA) or 6-mercaptopurine (6MP), could achieve clinical remission without steroids in steroid-dependent Crohn's disease (CD) patients.
Dr Marc Lemann and colleagues selected CD patients with active disease, despite treatment with prednisone (≥10 mg/d) for more than 6 months, for inclusion in the trial.
The research team treated all patients with either AZA (2 to 3 mg/kg/d) or 6MP (1 to 1.5 mg/kg/d).
Patients were divided into 2 strata:
- Patients who received AZA or 6MP at a stable dose for at least 6 months and still had active disease (CDAI >150) at inclusion (AZA failure).
- Patients not yet treated with AZA/6MP (naive).
There were 22 centers participating to the trial. From these centers 115 patients (63 female, mean age 30 years) were randomized, 56 to the AZA failure stratum and 59 to the naive stratum.
|75% of patients in the infliximab group were in remission at week 12.|
|American Gastroenterological Association|
Within each stratum, the team then randomized patients to receive either 3 infusions of infliximab (5 mg/kg) at day 0, week 2 and week 6, or 3 infusions of placebo.
During the 24 weeks of the study, if a clinical remission was achieved (CDAI <150), then the team tapered the steroids using a standardized scheme. In those patients who experienced a relapse, the team increased the dose of steroids until a new remission was achieved, and then they were tapered again.
The researchers set the primary end-point as remission off steroids at week 24.
The secondary end-points were remission without steroids at week 12, treatment failure due to steroid resistance, and a side-effect steroid score.
Of the 115 patients, 36% had Crohn's disease located in the colon, 14% in the small bowel, and 50% in both. The team found active perianal lesions were present in 22%.
At inclusion, patients had a mean CDAI of 189. The team determined that the median duration of steroid treatment was 15 months, and median dose of prednisone was 30 mg/d.
In stratum 1, median duration of AZA/6MP treatment was 24 months.
Overall, 57 patients were allocated to infliximab and 58 to placebo infusions.
The team found that 75% of patients in the infliximab group were in remission off steroids at week 12, compared with 38% in the placebo group. At week 24, 57% of the infliximab group were in remission off steroids, compared with 29% in the placebo group.
Treatment failure due to steroid resistance was less common in the infliximab group than in the placebo group (5% versus 23%, respectively).
The researchers did not identify any significant difference in infliximab efficacy between the 2 strata.
They determined that the median side-effect steroid score did not differ in the 2 groups at weeks 12 and 24.
The team identified severe adverse events in 2 patients in the infliximab group and in 4 patients in the placebo.
In their conclusion, the researchers suggested that infliximab may be used while waiting for the effect of AZA/6MP in steroid-dependent patients.
This strategy may be effective, even if AZA/6MP has previously failed, to allow steroid withdrawal.