Azathioprine maintenance treatment versus Infliximab maintenance treatment in Crohn's disease patients in remission

Crohn disease (CD) patients that have a flare of disease activity while on
immune suppressive (IS) medication (azathioprine (AZA), 6-mercaptopurine (6MP)
and methotrexaat) need additional treatment with infliximab (IFX). It remains
unclear when IFX treatment can be stopped. Subgroup analyses of the initial
trials on the effectiveness of IFX have shown better effectiveness for reaching
the endpoint of remission for the combination therapy. Therefore, patients are
treated with the IFX/IS combination for extended periods. Recently an alarming
rise in incidence of hepatosplenic T cell lymphomas in younger CD patients on
IFX/IS therapy has been noted. Concerns about the neoplastic complications of
IFX in combination with IS have highlighted the need to taper medication at
some point in the treatment. Obviously medication should only be tapered when
remission of disease is reached. It remains unclear whether either IFX or IS
should be stopped. Unpublished results from a trial by the Leuven group show
that continuing therapy with IFX alone in patients that are in remission for 6
months, is equally effective when compared with continuing IFX/IS combination
therapy. However, this study did not contain a treatment arm in which the IFX
was stopped and patients were maintained on IS alone. The effectiveness of AZA,
the IS agent tested by the Leuven group, in maintaining remission of disease is
well established and reputed by European guidelines. The costs of IFX
monotherapy by far exceed the costs of IS monotherapy.
The aim of this study is to compare the effectiveness of IS (AZA or 6MP)
monotherapy with IFX monotherapy in CD patients with quiescent disease, defined
by a Crohn*s Disease Activity Index (CDAI) below 150.
The study is designed as a multicenter randomized clinical trial including CD
patients with disease located in colon or the terminal ileum that have been in
remission while on IFX/IS combination therapy for at least 6 months. After
assessing mucosal healing by means of a colonoscopy patients will be stratified
for mucosal healing and randomized in to two treatment arms: continuing on IFX
monotherapy or continuing on the IS agent the patient already used before
randomization (AZA or 6MP). Outcomes are: number of relapses (primary outcome),
mucosal healing, number of treatment failures, and quality of life. To show
non-inferiority between IFX mono treatment and IS mono treatment 64 patients
per treatment arm are needed.
Patients will be recruited from June 2008 until June 2009 with a minimal
follow-up period of 1 year.

This study aims to show that the IFX or AZA are equally effective with the
latter being more efficient as maintenance therapy in CD after remission
induction with IFX/AZA for at least 6 months as defined by the proportion of
patients not needing more intense treatment due to relapse of disease.

Probe: Prospective, Randomised, Open treatment, Blind End-point evaluation

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The burden and risks associated with the treatments are subject of this study.
Participation does not impose other risks and the burden will be limited to a
minor time investment by the patient