SPARE Trial Shows Risks of Infliximab Withdrawal in Crohn's Patients on Combination Therapy - medtigo



SPARE Trial Shows Risks of Infliximab Withdrawal in Crohn’s Patients on Combination Therapy

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Therapeutic strategies for Crohn’s disease have evolved over the past decade, with mounting evidence that achieving deep remission is associated with better long-term outcomes. Combination therapy of infliximab and azathioprine is superior to either infliximab or azathioprine monotherapy in achieving clinical remission and endoscopic healing in azathioprine-naive patients.

However, once remission is achieved, physicians and patients must weigh the risks and benefits of continuing combination therapy with infliximab and an immunosuppressant.  

The risk of severe or opportunistic infections and lymphoproliferative disorders is of particular concern, with a consensus emerging that patients on combination therapy are at greater risk than those on monotherapy. Registry data suggest that de-escalation of drug therapy might reduce the risk of serious drug-related adverse events and provide cost savings.  

According to a recent study by The Lancet, the risk of disease relapse when discontinuing one or both drugs, or the risk of immunogenicity when discontinuing immunosuppressant therapy and continuing infliximab, is unclear. A randomized trial comparing the continuation of combination therapy versus immunosuppression of a control group and the overall time spent in clinical remission over the study period was not assessed.  

A recent placebo-controlled trial comparing infliximab withdrawal with infliximab continuation in patients in complete endoscopic remission confirmed a higher relapse rate in the infliximab withdrawal group. The study involved 50 patients, and those who were withdrawn from infliximab had a relapse rate of 50%, while those who continued taking the drug had no relapse. The role of concomitant immunosuppressant therapy was not explicitly examined in that study. 

The results of these studies have implications for the management of Crohn’s disease. Achieving deep remission is essential for long-term outcomes, and combination therapy with infliximab and azathioprine is effective in achieving this. However, the risks associated with continuing combination therapy must be carefully considered, including the risks of severe infections and lymphoproliferative disorders.  

De-escalation of drug therapy may be an option for some patients, as it can reduce the risk of serious drug-related adverse events and provide cost savings. However, the risks of disease relapse and immunogenicity when discontinuing immunosuppressant therapy and continuing infliximab are still unclear.  

Physicians and patients must carefully weigh the risks and benefits of different treatment options, considering the individual patient’s circumstances and disease severity. Future research is needed to understand better the risks and benefits of different treatment strategies for Crohn’s disease, including the role of concomitant immunosuppressant therapy.  

The study also showed that withdrawal of concomitant immunosuppressant therapy does not increase rates of disease relapse or anti-drug antibody formation in that continuing infliximab monotherapy. However, 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.  

Risk factors were also discovered for relapse and failure of therapy if patients were de-escalated from combination therapy. The findings suggest that in patients with Crohn’s disease receiving a combination of infliximab and concomitant immunosuppressant therapy, strategies for de-escalation can be considered in sustained steroid-free clinical remission after assessment of the risk of relapse and potential for effective retreatment in each individual.  


The study implies that treatment decisions should be tailored to each patient’s circumstances to optimize the balance of potential benefit and harm. The findings could improve safety and reduce the costs of treatment for Crohn’s disease without jeopardizing disease control. The study could also provide essential insights for developing more personalized treatment approaches for Crohn’s disease.  

Results from a recent study (SPARE trial) showed that patients with Crohn’s disease in clinical remission on combination therapy who discontinued infliximab experienced an increased risk of relapse over two years, as compared with those who continued infliximab either as monotherapy or in combination with immunosuppressant therapy.

However, the non-inferiority hypothesis for the time spent in remission over two years after infliximab withdrawal was rejected. Other predictors of relapse included young age at onset and evidence of ongoing inflammation at baseline assessment.

Retreatment with infliximab allowed rapid recapture and maintenance of remission in patients who relapsed, and treatment failure rates were similar across treatment groups. The study also found that discontinuing immunosuppressant therapy did not affect the relapse rate.

There was no significant change in endoscopic scores of activity, hs-CRP, or fecal calprotectin between baseline and end of study visit across groups, suggesting no signal for any subclinical disease escape during these two years of treatment de-escalation.

Infliximab trough levels at the end of the trial in the retreated patients were very similar to those observed at baseline, and patients who discontinued infliximab were in long-term remission and maintained on immunosuppressant therapy after infliximab withdrawal, which are two parameters that have been previously associated with a low risk of immunogenicity. 


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