Department of Rheumatology, Leiden University Medical Center, C-01-046, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Arthritis Res Ther. 2018 Apr 10;20(1):68. doi: 10.1186/s13075-018-1553-8.
Although infrequent, some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission. The absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA), is known to be associated with this outcome but further mechanisms underlying the chronic nature of RA are largely unknown. Magnetic resonance imaging (MRI)-detected bone marrow edema (BME), or osteitis, strongly predicts erosive progression and is associated with ACPA positivity. Therefore, we hypothesized that the presence of MRI-detected osteitis is also predictive of not achieving DMARD-free sustained remission and that the presence of osteitis mediates the association between ACPA and DMARD-free sustained remission.
A 1.5 T unilateral hand and foot MRI was performed at disease presentation in 238 RA patients, evaluating BME, synovitis, and tenosynovitis (summed as MRI inflammation score). DMARD-free sustained remission, defined as the absence of clinical synovitis after DMARD cessation that persisted during the total follow-up, was assessed (median follow-up 3.8 years). Associations between the different MRI-detected inflammatory features and this outcome were studied. A mediation analysis was performed to study whether the presence of BME mediated the association between ACPA and DMARD-free sustained remission. Finally, patterns of MRI-detected inflammation with regard to DMARD-free sustained remission were studied using partial least squares (PLS) regression.
Forty-six (19.3%) patients achieved DMARD-free sustained remission. ACPA positivity associated independently with remission (hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.06-0.39). In contrast, no associations were observed between MRI-detected BME (HR 0.99, 95% CI 0.94-1.03), or other MRI inflammatory features, and achieving DMARD-free sustained remission. Thus, the presence of BME did not mediate the association between ACPA and DMARD-free sustained remission. Furthermore, a PLS analysis revealed that patients who did or did not achieve remission could not be distinguished by patterns of MRI-detected inflammation.
At disease presentation, osteitis, as well as other MRI-detected inflammatory features, was not associated with achieving DMARD-free sustained remission over time. Thus, imaging predictors for joint damage and disease persistence differ. The processes mediating RA chronicity remain largely unsolved.
虽然并不常见，但一些类风湿关节炎（RA）患者可实现疾病缓解药物（DMARD）停药后持续缓解。已知 RA 特异性自身抗体（如抗瓜氨酸蛋白抗体（ACPA））的缺失与这种结果相关，但 RA 慢性本质的其他潜在机制仍知之甚少。磁共振成像（MRI）检测到的骨髓水肿（BME）或骨炎强烈预测侵蚀进展，并与 ACPA 阳性相关。因此，我们假设 MRI 检测到的骨炎的存在也可预测无法实现 DMARD 停药后持续缓解，并且骨炎介导了 ACPA 与 DMARD 停药后持续缓解之间的关联。
在 238 例 RA 患者的疾病发作时进行了 1.5T 单侧手部和足部 MRI 检查，评估了 BME、滑膜炎和腱鞘炎（总和为 MRI 炎症评分）。评估了 DMARD 停药后无临床滑膜炎且在总随访期间持续存在的 DMARD 停药后持续缓解（中位随访 3.8 年）。研究了不同 MRI 检测到的炎症特征与该结果之间的关系。进行了中介分析，以研究 BME 的存在是否介导了 ACPA 与 DMARD 停药后持续缓解之间的关联。最后，使用偏最小二乘（PLS）回归研究了 MRI 检测到的炎症模式与 DMARD 停药后持续缓解之间的关系。
46 例（19.3%）患者达到了 DMARD 停药后持续缓解。ACPA 阳性与缓解独立相关（风险比（HR）0.16，95%置信区间（CI）0.06-0.39）。相反，MRI 检测到的 BME（HR 0.99，95%CI 0.94-1.03）或其他 MRI 炎症特征与达到 DMARD 停药后持续缓解之间均无关联。因此，BME 的存在并未介导 ACPA 与 DMARD 停药后持续缓解之间的关联。此外，PLS 分析表明，达到或未达到缓解的患者无法通过 MRI 检测到的炎症模式区分。
在疾病发作时，骨炎以及其他 MRI 检测到的炎症特征与随着时间推移达到 DMARD 停药后持续缓解无关。因此，关节损伤和疾病持续存在的影像学预测指标不同。介导 RA 慢性的过程仍未得到充分解决。
