Gastroenterology

Gastroenterology

Volume 145, Issue 4, October 2013, Pages 766-774.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Early Azathioprine Therapy Is No More Effective Than Placebo for Newly Diagnosed Crohn's Disease

https://doi.org/10.1053/j.gastro.2013.06.009Get rights and content

Background & Aims

A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn's disease, yet little is known about the efficacy of early thiopurine therapy in adults.

Methods

We performed a prospective double-blind trial of adult patients with a recent (<8 weeks) diagnosis of Crohn's disease. Patients were randomly assigned to groups given azathioprine (2.5 mg · kg−1 · day−1, n = 68) or placebo (n = 63) at 31 hospitals from February 2006 to September 2009. Corticosteroids but no other concomitant medications were allowed for control of disease activity. The primary measure of efficacy was sustained corticosteroid-free remission.

Results

After 76 weeks of treatment, 30 patients treated with azathioprine (44.1%) and 23 given placebo (36.5%) were in sustained corticosteroid-free remission (difference of 7.6%; 95% confidence interval, −9.2 to 24.4%; P = .48). The rates of relapse (defined as Crohn's Disease Activity Index score >175) and corticosteroid requirements were similar between groups. A post hoc analysis of relapse, defined as a Crohn's Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01). Serious adverse events occurred in 14 patients in the azathioprine group (20.6%) and 7 in the placebo group (11.1%) (P = .16). A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation (20.6%) than in the placebo group (6.35%) (P = .02).

Conclusions

In a study of adults with Crohn's disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis. EudraCT 2005-001186-34.

Section snippets

Study Design

The AZathioprine for Treatment or Early Crohn's disease in adults (AZTEC) study (EudraCT 2005-001186-34) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial conducted in 31 Spanish hospitals under the auspice of the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) between February 2006 and September 2009. The investigational review board at each center approved the protocol, and all patients provided written informed consent

Patient Characteristics and Disposition

A total of 131 patients were randomized to treatment; 68 were assigned to azathioprine and 63 to placebo. The baseline characteristics of the patients were similar (Table 1); in all cases, the presence of active lesions was shown by endoscopy and/or magnetic resonance imaging within the 8 weeks before randomization. In keeping with the inclusion criteria that mandated inclusion of patients with new-onset disease and no internal penetrating or perianal fistulizing disease, none of the patients

Discussion

In this study performed in adults with new-onset CD, treatment with azathioprine within 8 weeks of diagnosis was not more effective than placebo for achieving long-term sustained corticosteroid-free remission. Although a number of predefined secondary efficacy measures pointed toward a benefit of azathioprine, these differences were not statistically significant. Only a post hoc analysis redefining the criteria for relapse as a CDAI score >220 showed that the proportion of patients experiencing

Acknowledgments

A list of investigators and centers of the AZTEC Study Group is provided in Appendix.

The authors thank Dr Brian G. Feagan for providing his insight and advice in the preparation of the manuscript as well as Dr Carlos Cara and UCB Pharma Iberica for supplying the study medication.

References (27)

Cited by (0)

Author names in bold designate shared co-first authorship.

Conflicts of interest The authors disclose no conflicts.

Funding Sponsored by Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa.

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