Gastroenterology

Gastroenterology

Volume 134, Issue 7, June 2008, Pages 1861-1868
Gastroenterology

Clinical–Alimentary Tract
Withdrawal of Immunosuppression in Crohn's Disease Treated With Scheduled Infliximab Maintenance: A Randomized Trial

https://doi.org/10.1053/j.gastro.2008.03.004Get rights and content

Background & Aims: The benefit to risk ratio of concomitant immunosuppressives with scheduled infliximab (IFX) maintenance therapy for Crohn's disease is an issue of debate. We aimed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label, randomized, controlled trial. Methods: Patients with controlled disease ≥6 months after the start of IFX (5 mg/kg intravenously) combined with immunosuppressives were randomized to continue (Con) or to interrupt (Dis) immunosuppressives, while all patients received scheduled IFX maintenance therapy for 104 weeks. Primary end point was the proportion of patients who required a decrease in IFX dosing interval or stopped IFX therapy. Secondary end points included IFX trough levels, safety, and mucosal healing. Results: A similar proportion (24/40, 60% Con) and (22/40, 55% Dis) of patients needed a change in IFX dosing interval or stopped IFX therapy (11/40 Con, 9/40 Dis). C-reactive protein (CRP) was higher and IFX trough levels were lower in the Dis group (Dis: CRP, 2.8 mg/L; interquartile range [IQR], 1.0–8.0; Con: CRP, 1.6 mg/L; IQR, 1.0–5.6, P < .005; trough IFX: Dis: 1.65 μg/mL; IQR, 0.54–3.68; Con: 2.87 μg/mL; IQR, 1.35–4.72, P < .0001). Low IFX trough levels correlated with increased CRP and clinical score. Mucosal ulcers were absent at week 104 in 64% (Con) and 61% (Dis) of evaluated patients with ongoing response to IFX. Conclusions: Continuation of immunosuppressives beyond 6 months offers no clear benefit over scheduled IFX monotherapy but is associated with higher median IFX trough and decreased CRP levels. The impact of these observations on long-term outcomes needs to be explored further.

Section snippets

Study Design

All patients ages 16 years or older and having received IFX in an episodic or systematic maintenance schedule were eligible if they had been treated with a combination of IFX 5 mg/kg IV dosed with intervals of 8 weeks or longer and an appropriate dose of immunosuppressives (azathioprine/6-mercaptopurine or methotrexate) for at least 6 months and provided they met all other inclusion criteria and none of the exclusion criteria. Appropriate dose of immunosuppressives was defined for azathioprine

Patient Demographics

Forty patients were included and randomized in each arm between February 2004 and May 2005 (Figure 1). As shown in Table 1, there were no differences between the groups for age, sex, smoking status, weight, duration of disease, baseline CDAI and CRP, disease location, duration of IFX or immunosuppressives therapy, type of immunosuppressive, and previous IFX maintenance strategy (Table 1). None of the patients had received a loading scheme with IFX 5 mg/kg at 0, 2, and 6 weeks because this

Discussion

The benefit of conventional immunosuppressives such as thiopurines and methotrexate in combination with scheduled IFX maintenance therapy is still debated. In this study, we aimed to investigate the additional benefit of immunosuppressives continuation in patients with luminal CD treated with scheduled IFX maintenance beyond the induction period. We found no advantage of continuing immunosuppressives for clinical outcomes including mucosal healing. However, the combined treatment approach

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    Support for study was not funded externally.

    Conflicts of interest that have been disclosed to study participants: Geert D'Haens, Paul Rutgeerts, and Gert Van Assche: Research support from Centocor and Schering Plough, Speaker's bureau of Schering Plough, consultancy for Centocor and Schering-Plough. Charlotte Magdelaine–Beuzelin: no conflict of interest. Filip Baert: no conflict of interest. Maja Noman: no conflict of interest. Séverine Vermeire: Speaker's bureau Schering-Plough. David Ternant: no conflict of interest. Hervé Watier: no conflict of interest. Gilles Paintaud: no conflict of interest. Paul Rutgeerts: Research support from Schering-Plough and Centocor.

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