Laboratory of Translational Gastroenterology, GIGA-institute, Liège University, Liège, Belgium
Department of Electrical Engineering and Computer Science, Liège University, Liège, Belgium.
Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648.
In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).
In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).
In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting 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).
In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.
NCT00571337 and NCT02177071.
在接受英夫利昔单抗和免疫抑制剂联合治疗并停用英夫利昔单抗的克罗恩病（CD）患者（来自英夫利昔单抗停药研究的队列，在联合免疫抑制剂治疗缓解期的 CD 患者中稳定缓解）中，短期（≤6 个月）和中/长期（>6 个月）复发的风险与不同的血液蛋白谱相关。我们的目的是在 SPARE 队列（一项前瞻性随机对照试验，比较在联合治疗中持续无激素缓解的 CD 患者中，英夫利昔单抗-抗代谢物联合治疗与抗代谢物单药治疗和英夫利昔单抗单药治疗）中验证这一发现的外部有效性。
在 SPARE 中，处于持续无激素临床缓解且正在接受联合治疗的 CD 患者被随机分配到三个治疗组：继续联合治疗、停用英夫利昔单抗或停用免疫抑制剂。在 STORI 和 SPARE（停用英夫利昔单抗组）队列的基线血清中，我们研究了 202 种免疫相关蛋白。使用单变量 Cox 模型比较了与复发时间相关的蛋白。通过一致性分析（ concordance 分析）评估生物标志物（单独和成对组合）的判别能力，并与 C 反应蛋白（CRP）、粪便钙卫蛋白和先前验证的模型（CEASE）进行比较。
在 STORI 和 SPARE 中，不同的血液蛋白谱与短期（例如高水平：CRP、结合珠蛋白、白细胞介素-6、C 型凝集素结构域家族 4 成员 C）和中/长期复发（例如低水平：Fms 相关酪氨酸激酶 3 配体、卡利斯塔丁、成纤维细胞生长因子 2）的风险相关。在外部验证中，前 10 个生物标志物对在预测短期（0.76-0.80 对 0.74 对 0.71 对 0.69，分别）和中/长期复发（0.66-0.68 对 0.61 对 0.52 对 0.59，分别）方面的表现优于 CEASE 模型、CRP 和粪便钙卫蛋白。
在停用英夫利昔单抗的 CD 患者中，我们证实短期和中/长期复发的风险与不同的血液蛋白谱相关，这表明其具有指导英夫利昔单抗停药的潜力。
NCT00571337 和 NCT02177071。
