Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial.
OBJECTIVE
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 > or = 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 microg/mL; IQR, 0.54-3.68; Con: 2.87 microg/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.
Van Assche
Gert
G
Division of Gastroenterology, University of Leuven Hospitals, Leuven, Belgium. gert.vanassche@uz.kuleuven.be
Magdelaine-Beuzelin
Charlotte
C
D'Haens
Geert
G
Baert
Filip
F
Noman
Maja
M
Vermeire
Séverine
S
Ternant
David
D
Watier
Hervé
H
Paintaud
Gilles
G
Rutgeerts
Paul
P
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001379:Azathioprine / Q000008:administration & dosage; D001530:Belgium; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D000069285:Infliximab; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D000069285:Infliximab; D015122:Mercaptopurine; D001379:Azathioprine; D008727:Methotrexate