Two new studies of azathioprine use in early Crohn’s disease challenge the notions that the drug has utility in achieving and prolonging remission, respectively.
However, the drug may have efficacy in subsets of patients with severe disease and with perianal disease, the authors reported in the October issue of Gastroenterology.
In the first study, led by Dr. Julián Panés, of the Hospital Clínic/IDIBAPS in Barcelona, 131 patients were randomized to receive either azathioprine or placebo. In total, 37 patients in the azathioprine group and 32 in the placebo group completed the 18-month trial.
Patients ranged in age from 18 to 70 years and had been diagnosed with Crohn’s disease within 8 weeks of screening.
Dr. Panés and his colleagues found that overall, the proportion of patients with sustained corticosteroid-free remission was similar for both treatment groups: 44.1% of azathioprine patients and 36.5% of placebo patients (P = .48) (Gastroenterol. 2013 [doi: 10.1053/j.gastro.2013.06.009]).
Nor was there any marked difference in the proportions of patients who achieved sustained corticosteroid-free remission at earlier time points, or who achieved relapse-free survival.
One area in which the drug did show benefit, however, was found in a post hoc analysis, wherein the definition of relapse was refined from a Crohn’s Disease Activity Index (CDAI) score of 175 or greater to a score in excess of 220.
By this measure, azathioprine patients showed lower relapse rates than placebo patients (11.8% vs. 30.2%; P = .01), leading Dr. Panés to conclude that there may be a "potential benefit of the drug in patients with more severe disease."
The second study, by Dr. Jacques Cosnes, of the Hôpital Saint-Antoine and Université Pierre et Marie Curie, both in Paris, also looked at adults with newly diagnosed Crohn’s disease (less than 6 months).
He and his colleagues randomly assigned 147 patients to initial azathioprine or to "conventional management," which included azathioprine only in cases of corticosteroid dependency, chronic active disease with frequent flares, poor response to corticosteroids, or development of severe perianal disease. A total of 132 patients completed the study.
The primary endpoint in this study was the proportion of trimesters spent in corticosteroid-free and anti–tumor necrosis factor–free remission over the 3 years of the study period.
Dr. Cosnes and his colleagues found that 67% of trimesters were spent in remission among the 65 patients in the early azathioprine group, compared with 56% among the 67 patients in the conventional management group (P = .69), with clinical remission in this case defined as a CDAI score of less than 150 (Gastroenterol. 2013 [doi: 10.1053/j.gastro.2013.04.048]).
Additionally, "Overall, patients in the early azathioprine group had a similar proportion of trimesters with flare, hospitalization, intestinal surgery, and use of anti-TNF therapy compared with patients in the conventional management group, but had less active perianal lesions," the researchers wrote.
Indeed, while only two patients in the azathioprine group required perianal surgery, nine underwent the procedure in the conventional management group, although there was no difference in patients remaining free of intestinal surgery between the two groups, they added.
"The efficacy of azathioprine for maintenance of remission in patients with Crohn’s disease, albeit modest ... is well established when used at the appropriate dosage and duration," Dr. Cosnes and his colleagues wrote.
"However, it has been claimed that this effect may be jeopardized if azathioprine is prescribed too late, at a time when irreversible damage has already occurred."
And while this study showed no benefit of early induction of azathioprine, except in cases of perianal disease, this "beneficial effect ... needs to be confirmed by another study before recommending early initiation of azathioprine therapy in patients with rectal involvement and/or perianal lesions at diagnosis."
Dr. Panés and his fellow investigators disclosed no personal conflicts of interest relating to this study; their work was sponsored by the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa. Dr. Cosnes and his fellow investigators reported financial ties to numerous pharmaceutical makers, including the makers of azathioprine. Their work was supported by the Association François Aupetit and the Société Nationale Française de Gastroentérologie.
