Crohn’s disease (CD) is a chronic, immune-mediated, inflammatory disease affecting gastro-intestinal tract, arising from an interaction between genetic & environmental factors. CD is characterized by recurrent attacks alternating with remission periods. Flares & chronicity have impact on patient’s Quality of Life (QoL) (co-morbidities, linked to CD itself, adverse events due to treatments). Curative therapies do not yet exist. Current best treatments are symptoms relieving therapies. The gold standard is the combination of anti-TNF/antimetabolites, a significant progress in CD treatment with an influence on clinical practice. This is Combo Therapy (CT), with a demonstrated efficacy in clinical trials. CT is thought best used at early-stage of CD without interruption & if needed, with dose escalation. However, antimetabolites & anti-TNF are associated with life-threatening side-effects & biologic treatments represent up to 50% of Inflammatory Bowel Disease (IBD) medical costs. There is an unmet need to improve safety & costs while maintaining treatment efficacy. Despite this, treatment de-escalation to monotherapy has received limited attention. In EU, 3M people are affected by IBD, with a worldwide increase of CD incidence. CD can’t be cured, its chronicity affects patients on personal, family & socio-professional plans, with high impact as they are often diagnosed at a young age & ill health may be lifelong. QoL is also impacted: each year, 15-20% of CD patients are hospitalized, with 57-80% for surgical interventions. The economic burden is estimated to 16.7BN€/year in EU & 15.5BN$ in US. Optimal long-term (LT) treatment is to maximize disease control & QoL & to decrease direct/indirect costs. Beyond that, one can assume information collected in CD could be extrapolated to other Immune Mediated Inflammatory diseases (IMIDs), involving same kind of drugs & treatment strategies. BIOCYCLE objective is to assess benefits/risks of an innovative regimen, optimizing LT treatment compared to current gold standard (monotherapy). The new one consists in including Treatment Cycles (after reaching deep & prolonged remission), which alternate periods with both drugs & periods where one of them is withdrawn, to improve safety & costs while maintaining same level of therapy efficacy. To assess & validate the suitability & implementation of this concept, the Project targets specific objectives. We will generate & collect clinical & biomarkers data [SPARE study: 3 arms-controlled clinical trial with 210-220 CD patients in stable remission under CT to compare anti-TNF or antimetabolites withdrawal to CT maintenance]; cost-of-illness/cost-effectiveness & patients’, caregivers’ & healthcare systems’ perceptions on Treatment Cycles. A critical appraisal of the new regimen & its impact on CD management will be performed, leading to recommendations & decision-making tools to optimize the maintenance therapy in function of patients’ needs & characteristics.