Background and aims: In Crohn’s disease (CD) patients on combination therapy (infliximab and immunosuppressant) and stopping infliximab (STORI cohort), the risk of short-term (<6 months) and mid/long-term relapse (>6 months) was associated with specific blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort. Methods: The SPARE trial included patients with CD in sustained steroid-free clinical remission, on combination therapy and randomly allocated to one of three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. As it was performed in STORI, 202 immune-related proteins were measured in the baseline serum of SPARE (arm stopping infliximab, n=63-67). The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The external validation of biomarkers (individually and combined by pairs) was evaluated by a discrimination analysis (c-statistic) and compared to CRP, faecal calprotectin and a previously validated model (CEASE). Results: In STORI and SPARE, specific blood protein profiles were associated with the risk of short-term (eg, high level: CRP, HP, IL6, CLEC4C, 3.5<HR<17.5, p<0.05) and mid/long-term relapse (eg, low level: FLT3LG, SERPINA4, FGF2, 0.15<HR<0.36, p<0.05). At external validation, our top 10 biomarker pairs showed a higher discriminative ability (c-statistic) than the CEASE model, CRP and faecal calprotectin to predict short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively ) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively). Conclusion: In CD patients stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with specific blood protein profiles showing the potential to guide infliximab withdrawal.