Alivernini Stefano, Tolusso Barbara, Gessi Marco, Gigante Maria Rita, Mannocci Alice, Petricca Luca, Perniola Simone, Di Mario Clara, Bui Laura, Fedele Anna Laura, Capacci Annunziata, Bruno Dario, Peluso Giusy, La Torre Giuseppe, Federico Francesco, Ferraccioli Gianfranco, Gremese Elisa
Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, and Università Cattolica del Sacro Cuore, Rome, Italy.
Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
Arthritis Rheumatol. 2021 Sep;73(9):1601-1613. doi: 10.1002/art.41726. Epub 2021 Aug 9.
This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients.
The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation.
The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28.
The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.
本研究应用在常规护理期间从类风湿关节炎(RA)患者以及患有其他炎性和非炎性关节疾病的患者的超声(US)引导下的滑膜组织(ST)活检中获得的滑膜炎评分,以识别与疾病特征相关的治疗前滑膜生物标志物,并将这些结果整合到一个多参数列线图中,用于初治类风湿关节炎(RA)患者的诊断和治疗反应的基线预测。
该研究共纳入1015例患有各种自身免疫性疾病的患者(545例RA患者、167例银屑病关节炎[PsA]患者、199例未分化外周炎性关节炎[UPIA]患者、18例晶体诱导性关节炎患者、26例结缔组织病患者以及60例骨关节炎[OA]患者[作为SYNGem队列的一部分])。所有患者在基线时均接受了US引导下的ST活检,然后根据疾病阶段进行分层。将KSS以及疾病特征和临床结局纳入一个列线图,以预测先前未接受过治疗的RA患者实现临床缓解的情况。在应用治疗达标策略的患者中,缓解定义为治疗开始后6个月时28个关节的疾病活动评分(DAS28)的变化。
与OA患者相比,RA患者以及PsA患者和UPIA患者的KSS存在显著差异。在RA中,KSS与DAS28直接相关,并且与初治RA患者的自身抗体阳性有关。此外,在基线时,根据DAS28在6个月时实现缓解的初治RA患者的KSS较低、症状持续时间较短(极早期RA[VERA])且疾病活动度较低,而根据DAS28未实现缓解的初治RA患者则不然。逻辑回归分析结果确定了以下6个月时基于DAS28实现疾病缓解的协同预测因素:疾病持续时间短(VERA)、疾病活动度不高以及基线时KSS<5。将这些基线临床和组织学特征整合到初治RA患者的列线图中,根据DAS28,实现6个月缓解的概率高达81.7%。
KSS是在US引导下的ST活检中评估滑膜炎的可靠工具,这取决于疾病阶段和每个患者的自身免疫情况。该工具可整合到一个治疗反应预测列线图中,用于预测先前未接受过治疗的RA患者的治疗反应。