Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission.
Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission.
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DOI：
10.1038/s41598-021-86335-7
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发表时间：
2021-03-25
影响因子：
4.6
通讯作者：
Ogura T
中科院分区：
文献类型：
--
作者：
Kameda H;Hirata A;Katagiri T;Takakura Y;Inoue Y;Takenaka S;Ito H;Mizushina K;Ogura T
为了阐明类风湿关节炎（RA）在停用生物疾病缓解抗风湿药物（bDMARD）后的疾病爆发过程，我们首先关注达到严格缓解标准后的RA爆发预测。2014年11月至2018年1月期间在我们日本东京医疗中心维持简化疾病活动指数≤ 3.3 ≥ 3个月的RA患者符合资格。主要终点是bDMARD停药后2年内的发作（疾病活动评分28-红细胞沉降率≥ 3.2，较基线增加> 0.6）。每2-3个月进行一次全面的临床评估，对40个关节进行超声检查评价，并对12种生物标志物进行血液采样，持续2年，除非患者发生发作。使用单变量和Kaplan-Meier分析比较了耀斑阳性和耀斑阴性患者。入组了36例患者（80.6%为女性，中位疾病持续时间为5.2年;中止bDMARD的中位治疗期为2年;中位缓解持续时间为18个月）。20例患者（55.6%）在bDMARD首次跳过日期后43-651天（中位数，115）发生RA发作。两名没有疾病发作而退出的患者被排除在比较之外。临床和超声评价未显示组间显著差异; Kaplan-Meier分析显示较高的基线可溶性肿瘤坏死因子受体1（sTNFR 1）浓度影响随后的疾病发作（p = 0.0041）;较高的基线白细胞介素（IL）-2浓度仅对sTNFR 1较低的患者有益（p = 0.0058），导致83.3%的sTNFR 1较低和IL-2较高的患者维持缓解。我们证明了联合生物标志物评估对预测RA患者bDMARD停药后持续缓解的有效性。
To elucidate the disease-flare process in rheumatoid arthritis (RA) after discontinuing biological disease-modifying antirheumatic drugs (bDMARDs), we first focused on RA-flare prediction after achieving stringent remission criteria. Patients with RA who maintained a simplified disease activity index ≤ 3.3 for ≥ 3 months during November 2014–January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28—erythrocyte sedimentation rate ≥ 3.2 with increase from baseline > 0.6) within 2 years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2–3 months for 2 years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan–Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2 years; median treatment period with discontinued bDMARD, 2 years; median remission duration, 18 months) were enrolled. Twenty patients (55.6%) experienced RA flare 43–651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan–Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p = 0.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p = 0.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.
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影响因子：
27.4
作者：
Emery P;Burmester GR;Bykerk VP;Combe BG;Furst DE;Barré E;Karyekar CS;Wong DA;Huizinga TW
通讯作者：
Huizinga TW
影响因子：
27.4
作者：
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Klatzmann, David
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通讯作者：
Schett G
影响因子：
27.4
作者：
Fautrel, Bruno;Thao Pham;Tubach, Florence
通讯作者：
Tubach, Florence
影响因子：
27.4
作者：
Haschka, Judith;Englbrecht, Matthias;Rech, Juergen
通讯作者：
Rech, Juergen