We have completed surveys on caregiver’s, healthcare authorities’ and patients’ perceptions on Treatment Cycles concept. It highlighted some key points: (1) important variations exist across patients and practitioners emphasizing the necessity of a personalized approach (2) Although patients and doctors put the priority on the control of the disease and the absence of flare, because of a fear of side effects, a substantial part would accept a small risk of relapse and some time with active disease to de-escalate therapy.
We have completed the SPARE study, a 3 arms-controlled clinical trial comparing continuous Combo Therapy (CT) to anti-TNF or anti-metabolites withdrawal, in moderate-severe CD patients in sustained remission under CT. More than 70 sites have been initiated in 7 countries (FR, UK, BE, SW, AU, DE, NL), 252 patients have been screened and 211 randomized. The two co-primary end-points and major secondary endpoints have been analysed and published. Our results allowed to draw a series of major conclusions: 1) we confirmed the higher relapse rate in patients stopping their biologic treatment (infliximab), 2) there was no increase in relapse rate in patients stopping their anti-metabolite/immunosuppressant, 3) the treatment strategy failure rate was similar across the three groups, 4) the time spent in remission over two years was only marginally lower in patients stopping their biologic. Overall, these results highlight the fact that biologic treatment withdrawal after longstanding steroid-free remission in CD, should not be systematic, but that some patients may be candidates for such withdrawal. Very promising markers to help and better determine the subgroup of patients who would be best candidates for treatment withdrawal have been identified. In particular, the risk of short term relapse was associated with the persistence of and increased blood concentration of acute phase reactants and markers of ongoing inflammation, while the longer term relapse (beyond 6 months) was associated with a more heterogenous pattern, including increased or decreased concentration of proteins involved in immune regulation, and the intestinal barrier function.
We have developed a pharmacoeconomic simulation model mimicking SPARE study and assessing treatment cycles concept. This model was populated with existing literature data. Sensitivity analyses were performed allowing preliminary conclusions on this pharmacoeconomic aspect. This model has now also been fed with the SPARE data. The first analyses bring some nuances to the conclusions of the theoretical model and highlights the conditions in which treatment cycles may become the most cost-effective strategy.
We have collected and synthesized arguments to build a structured pathway of care and such a dedicated pathway of care for treatment de-escalation in CD has been developed, allowing patients, doctors, and healthcare systems to contribute to complex decision in CD management, like the one of treatment de-escalation.
Finally, we have organized a European consensus conference on the topic of treatment de-escalation in Crohn’s disease based on the methodology of the ECCO topical reviews. A full manuscript has been published, three dissemination meetings were organized across Europe and e-learning tools are available for the inflammatory bowel disease community on the ECCO website.
