Fitton John, Melville Andrew, Naraghi Kamran, Nam Jacqueline, Dass Shouvik, Emery Paul, Buch Maya H
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital.
Department of Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds.
Rheumatol Adv Pract. 2022 Aug 1;6(2):rkac057. doi: 10.1093/rap/rkac057. eCollection 2022.
The aim was to evaluate the proportion of RA patients who are refractory to multiple targeted therapies (TTs) in a real-world cohort of patients in a tertiary rheumatology referral centre, to describe patterns of drug sequencing associated with the development of refractory RA (RefRA) and to identify whether there is a subgroup of RefRA patients in whom successive drugs have shown primary lack of efficacy.
Patients at a single centre were defined as refractory if they had failed two or more classes of TT and were identified from a dedicated TT clinic database. Reasons for drug failure were recorded, and patients were categorized pragmatically as having mild [failure of two biologic DMARD (bDMARD) classes], moderate [failure of at least three bDMARD classes] or severe [failure of at least two bDMARD classes and JAK inhibitor] refractory disease.
One hundred and seventy-two patients were identified as RefRA (>10% of our TT-exposed cohort); median [interquartile range (IQR)] TT exposures of four (two), 81.5% female, 82% seropositive, mean (s.d.) age of 63 (12.3) years. Detailed analysis of 60 patients showed a median (IQR) disease duration of 22 (10.75) years, median (IQR) time from diagnosis to initiation of first TT of 5 (10) years, and mean (s.d.) baseline DAS28CRP before starting first-line TT of 5.91 (0.84). Among RefRA patients, 15% were severely refractory, and 6% had demonstrated no clinical response to any TT.
A small proportion of patients have true RefRA. Most patients fail multiple therapies owing to a combination of inefficacy and adverse events.
本研究旨在评估在一家三级风湿病转诊中心的真实世界患者队列中，对多种靶向治疗（TTs）难治的类风湿关节炎（RA）患者的比例，描述与难治性RA（RefRA）发生相关的药物序贯模式，并确定是否存在一个连续使用的药物均显示出原发性疗效不佳的RefRA患者亚组。
单中心患者若对两类或更多类TTs治疗失败，则被定义为难治性患者，这些患者从一个专门的TT诊所数据库中识别出来。记录药物失败的原因，并根据实际情况将患者分为轻度（两类生物性改善病情抗风湿药[bDMARDs]治疗失败）、中度（至少三类bDMARDs治疗失败）或重度（至少两类bDMARDs治疗失败且使用过JAK抑制剂）难治性疾病。
172例患者被确定为RefRA（占我们接受TT治疗队列的10%以上）；TT治疗的中位[四分位间距（IQR）]为4（2）次，81.5%为女性，82%为血清学阳性，平均（标准差）年龄为63（12.3）岁。对60例患者的详细分析显示，疾病中位（IQR）病程为22（10.75）年，从诊断到开始首次TT治疗的中位（IQR）时间为5（10）年，开始一线TT治疗前的平均（标准差）基线DAS28CRP为5.91（0.84）。在RefRA患者中，15%为重度难治性患者，6%对任何TT治疗均无临床反应。
一小部分患者存在真正的RefRA。大多数患者因疗效不佳和不良事件的综合作用而多种治疗失败。
