Use of 6-Mercapturine/Azathioprine as the Immunomodulator of Choice for Moderately Active Crohnʼs Disease

The efficacy of 6-mercaptopurine (6-MP) and its prodrug, azathioprine (AZA), in maintaining clinical remission in Crohn's disease has been clearly documented by metaanalyses1 of randomized controlled trial data accrued in adults. There is similar Level I evidence of efficacy for these immunomodulatory drugs as steroid-sparing agents in controlling intestinal inflammation in pediatric patients.2 Indeed, AZA/6-MP therapy has become a mainstay of the management of pediatric and adult Crohn's disease, a reflection of the increased body of evidence in support of both the therapeutic efficacy and safety profiles of these drugs. The subject of this debate, however, is whether AZA/6-MP should be included in the first-line therapy from the time of diagnosis in all patients presenting with “moderately active” Crohn's disease. The heterogeneity of the phenotypic expression of Crohn's disease and its variable natural history, considered in combination with the potential drug toxicities, do not support such a blanket recommendation. The best available evidence for this debate comes from the multicenter randomized controlled trial of Markowitz et al.2 Over the course of 7 years at 18 pediatric institutions, 55 children and adolescents newly recognized to have Crohn's disease of at least moderate severity were randomized to receive as first treatment either prednisone plus placebo or prednisone plus 6-MP. A comparison of the rates of clinical relapse over the subsequent 18 months supports the use of 6-MP to maintain remission and spare the use of steroids.2 Nevertheless, 50% of the children treated at diagnosis with a course of prednisone remained in continuous clinical remission at 12 months, and even at 18 months, without receiving any concomitant therapy.2 As otherwise stated, more than one-half of the children remaining in clinical remission during 6-MP therapy would have remained as well without receiving it. One-half of the young patients with moderately severe Crohn's disease at diagnosis were given an immunomodulatory drug unnecessarily. Moreover, the rates of linear growth, a very important outcome variable in assessing the efficacy of any therapy in children, seemed comparable in both the group treated with 6-MP and in the control (placebo-treated) group.2 The control of intestinal symptoms and the reduction in steroid usage achieved with 6-MP were not associated with improved growth.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.