Research in context
anti-TNFα, Crohn's disease
DISEASE, REMISSION, CROHN'S DISEASE

A treat-to-target strategy and tight disease control have been shown to improve outcomes in Crohn's disease. However, this approach might necessitate long-term use of both biological drugs and immunosuppressant therapy. Combination therapy of anti-TNFα with either thiopurines or methotrexate is well established in this context but is associated with long-term risks and health-care costs. It is not well established whether treatment de-escalation from combination therapy, once sustained steroid-free remission has been achieved, is feasible, nor whether this approach could improve safety and reduce costs without jeopardising disease control. Infliximab withdrawal in patients with Crohn's disease in sustained steroid-free remission has been associated with an increased risk of relapse approximating 50% over 2 years in uncontrolled studies. These studies also provided evidence that remission can be recaptured in most patients by resuming treatment with infliximab, in particular when immunosuppressant therapy had been continued. Other uncontrolled data have concluded that withdrawal of immunosuppressant therapy in patients who had achieved durable remission on combination therapy might not alter relapse rates.
In this randomised controlled study, we confirmed and quantified the increased risk of relapse and loss of time in remission in patients on combination therapy who were randomly assigned to discontinue infliximab, compared with those randomly assigned to continue infliximab in the context of either monotherapy or combination therapy. We demonstrated that immunosuppressant therapy withdrawal was not associated with an increased risk of relapse, nor of drug immunogenicity. We defined risk factors for relapse and for failure of therapy if patients were de-escalated from combination therapy. We also demonstrated that most patients experiencing relapse after infliximab withdrawal rapidly responded to re-treatment and maintained remission over 2 years.
In patients with Crohn's disease receiving combination infliximab and concomitant immunosuppressant therapy, strategies for treatment de-escalation can be considered in sustained steroid-free clinical remission after assessment of the risk of relapse and potential for effective re-treatment in each individual. Withdrawal of concomitant immunosuppressant therapy does not increase rates of disease relapse or anti-drug antibody formation in those continuing infliximab monotherapy. Withdrawal of infliximab is associated with an increased risk of relapse, but the effects of relapse can be effectively and rapidly treated in most patients. Treatment decisions should be tailored to each patient's circumstances to optimise the balance of potential benefit and harm.