Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Bristol-Myers Squibb, Princeton, NJ, USA.
Rheumatology (Oxford). 2022 Dec 23;62(1):124-134. doi: 10.1093/rheumatology/keac294.
Although sustained DMARD-free remission (SDFR; sustained absence of clinical-synovitis after DMARD-discontinuation) is increasingly achievable in RA, prevalence differs between ACPA-negative (40%) and ACPA-positive RA (5-10%). Additionally, early DAS remission (DAS4months<1.6) is associated with achieving SDFR in ACPA-negative, but not in ACPA-positive RA. Based on these differences, we hypothesized that longitudinal patterns of local tissue inflammation (synovitis/tenosynovitis/osteitis) also differ between ACPA-negative and ACPA-positive RA patients achieving SDFR. With the ultimate aim being to increase understanding of disease resolution in RA, we studied MRI-detected joint inflammation over time in relation to SDFR development in ACPA-positive RA and ACPA-negative RA.
A total of 198 RA patients (94 ACPA-negative, 104 ACPA-positive) underwent repeated MRIs (0/4/12/24 months) and were followed on SDFR development. The course of MRI-detected total inflammation, and synovitis/tenosynovitis/osteitis individually were compared between RA patients who did and did not achieve SDFR, using Poisson mixed models. In total, 174 ACPA-positive RA patients from the AVERT-1 were studied as ACPA-positive validation population.
In ACPA-negative RA, baseline MRI-detected inflammation levels of patients achieving SDFR were similar to patients without SDFR but declined 2.0 times stronger in the first year of DMARD treatment [IRR 0.50 (95% CI; 0.32, 0.77); P < 0.01]. This stronger decline was seen in tenosynovitis/synovitis/osteitis. In contrast, ACPA-positive RA-patients achieving SDFR, had already lower inflammation levels (especially synovitis/osteitis) at disease presentation [IRR 0.45 (95% CI; 0.24, 0.86); P = 0.02] compared with patients without SDFR, and remained lower during subsequent follow-up (P = 0.02). Similar results were found in the ACPA-positive validation population.
Compared with RA patients without disease resolution, ACPA-positive RA patients achieving SDFR have less severe joint inflammation from diagnosis onwards, while ACPA-negative RA patients present with similar inflammation levels but demonstrate a stronger decline in the first year of DMARD therapy. These different trajectories suggest different mechanisms underlying resolution of RA chronicity in both RA subsets.
虽然在类风湿关节炎（RA）中越来越能够实现持续的疾病缓解（即停止使用 DMARD 后持续无临床滑膜炎），但抗环瓜氨酸肽（ACPA）阴性（40%）和 ACPA 阳性（5-10%）RA 之间的患病率存在差异。此外，早期 DAS 缓解（DAS4 个月<1.6）与 ACPA 阴性 RA 中实现 SDFR 相关，但与 ACPA 阳性 RA 无关。基于这些差异，我们假设在实现 SDFR 的 ACPA 阴性和 ACPA 阳性 RA 患者中，局部组织炎症（滑膜炎/腱鞘炎/骨炎）的纵向模式也存在差异。最终目标是增加对 RA 疾病缓解的理解，我们研究了与 ACPA 阳性 RA 和 ACPA 阴性 RA 中 SDFR 发展相关的时间上的 MRI 检测到的关节炎症。
共有 198 名 RA 患者（94 名 ACPA 阴性，104 名 ACPA 阳性）接受了重复 MRI（0/4/12/24 个月），并在 SDFR 发展方面进行了随访。使用泊松混合模型比较了在实现 SDFR 和未实现 SDFR 的 RA 患者之间，MRI 检测到的总炎症以及滑膜炎/腱鞘炎/骨炎的个体的病程。总共，从 AVERT-1 研究中研究了 174 名 ACPA 阳性 RA 患者作为 ACPA 阳性验证人群。
在 ACPA 阴性 RA 中，实现 SDFR 的患者的基线 MRI 检测到的炎症水平与未实现 SDFR 的患者相似，但在 DMARD 治疗的第一年下降了 2 倍[IRR 0.50（95% CI；0.32，0.77）；P<0.01]。这种更强的下降发生在腱鞘炎/滑膜炎/骨炎中。相比之下，在疾病发病时，实现 SDFR 的 ACPA 阳性 RA 患者的炎症水平已经较低（尤其是滑膜炎/骨炎）[IRR 0.45（95% CI；0.24，0.86）；P=0.02]，并且在随后的随访中保持较低（P=0.02）。在 ACPA 阳性验证人群中也发现了类似的结果。
与未实现疾病缓解的 RA 患者相比，实现 SDFR 的 ACPA 阳性 RA 患者从诊断开始就具有更严重的关节炎症，而 ACPA 阴性 RA 患者的炎症水平相似，但在 DMARD 治疗的第一年下降更明显。这些不同的轨迹表明，在这两个 RA 亚组中，RA 慢性缓解的潜在机制不同。
