Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Rheumatology, Meander Medical Center, Amersfoort, The Netherlands.
Rheumatology (Oxford). 2021 Aug 2;60(8):3778-3788. doi: 10.1093/rheumatology/keaa860.
Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease.
Consecutive RA patients were enrolled and categorized as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis.
Fifty-two RA patients were classified as D2T and 100 as non-D2T. Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA [odds ratio (OR) 1.97 (95%CI 1.08-3.61)]. Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than in non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient's and rheumatologist's wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: (i) 'non-adherent dissatisfied patients'; (ii) patients with 'pain syndromes and obesity'; (iii) patients closest to the concept of 'true refractory RA'.
This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.
治疗难治性（D2T）类风湿关节炎（RA）患者通常基于反复试验，由于多种因素的影响，治疗可能具有挑战性。本研究旨在确定 RA 发病时的危险因素、促成因素和疾病负担。
连续招募 RA 患者，并根据 EULAR 定义将其分为 D2T 或非 D2T（对照组）。评估可能导致 D2T RA 发生的因素和疾病负担。通过逻辑回归确定 RA 发病时的危险因素和与 D2T RA 相关的独立因素。通过聚类分析探讨 D2T RA 亚组。
52 例 RA 患者被归类为 D2T，100 例为非 D2T。发病时较低的社会经济地位被确定为发展为 D2T RA 的独立危险因素[比值比（OR）1.97（95%可信区间 1.08-3.61）]。一些促成因素与 D2T RA 相关，在 D2T 患者中比在非 D2T 患者中更常见：由于不良反应（94%比 57%）或合并症（69%比 37%）导致药物选择受限、患者与风湿病医生对强化治疗的意愿不匹配（37%比 6%）、合并纤维肌痛（38%比 9%）和应对能力较差（更差的水平）。D2T RA 患者的疾病负担显著更高。确定了 D2T RA 的三个亚组：（i）“不依从且不满意的患者”；（ii）“疼痛综合征和肥胖症患者”；（iii）“最接近‘真正难治性 RA’概念的患者”。
这项关于 D2T RA 的综合研究显示了多种促成因素、较高的疾病负担和 D2T RA 的异质性。这些发现表明，在日常实践中应识别这些因素，以便进一步针对个体患者制定治疗策略。
