Real-World Outcomes Associated With Methotrexate, Sulfasalazine, and Hydroxychloroquine Triple Therapy Versus Tumor Necrosis Factor Inhibitor/Methotrexate Combination Therapy in Patients With Rheumatoid Arthritis
Real-World Outcomes Associated With Methotrexate, Sulfasalazine, and Hydroxychloroquine Triple Therapy Versus Tumor Necrosis Factor Inhibitor/Methotrexate Combination Therapy in Patients With Rheumatoid Arthritis
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DOI：
10.1002/acr.24253
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发表时间：
2021-08-01
影响因子：
4.7
通讯作者：
Kremer, Joel M.
中科院分区：
文献类型：
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作者：
Curtis, Jeffrey R.;Palmer, J. Lynn;Kremer, Joel M.
目的虽然随机对照试验已经证明三联疗法（甲氨蝶呤[MTX]，柳氮磺胺吡啶[SSZ]和羟氯喹[HCQ]）与联合疗法（肿瘤坏死因子抑制剂[TNFi]和MTX）相比具有相对可比的临床结局，但对这些策略进行比较的真实世界经验尚未得到充分研究。方法我们评估了在Corrona RA药物安全性和有效性登记处登记的类风湿关节炎（RA）患者中MTX/SSZ/HCQ三联疗法与TNFi/MTX联合疗法的临床有效性和停药效果。使用倾向评分匹配以1：3的比例匹配患者，以调整治疗组之间的不平衡，并根据研究受试者的生物制剂初治或生物制剂暴露状态进行分层。结果符合本研究分析条件的患者包括生物制剂初治RA患者（3，926例接受TNFi/MTX联合治疗，262例接受MTX/SSZ/HCQ三联治疗）和生物制剂暴露RA患者（3，365例接受TNFi/MTX联合治疗，130例接受MTX/SSZ/HCQ三联治疗）。在倾向评分匹配之前，治疗组之间的许多因素不平衡，三联治疗患者通常年龄较大，RA病程较长，RA疾病活动度较低，更可能有恶性肿瘤和其他合并症病史。匹配后，几乎所有（93-98%）三联疗法患者可与TNFi/MTX疗法患者匹配，且队列特征通常平衡良好。三联疗法患者的停药率高于TNFi/MTX治疗患者（生物制剂初治组的校正风险比[HR]为2.17 [95%置信区间1.63-2.88];生物制剂暴露组的校正HR为1.51 [95%置信区间1.06-2.15]）。在6个月时，TNFi/MTX治疗组中达到低疾病活动度的生物制剂初治患者比例显著更高（TNFi/MTX治疗患者为49.2%，三联治疗患者为33.3%），临床疾病活动指数评分的平均变化也是如此（-9.3单位vs-5.5 [95%置信区间-1.5，-6.1]）。与三联疗法相比，生物制剂暴露患者的相应结果在数值上支持TNFi/MTX疗法，但未达到统计学显著性。结论MTX/SSZ/HCQ三联疗法在美国临床应用较少。在本研究中，与TNFi/MTX治疗患者相比，三联治疗患者的药物持久性和临床有效性结果不太有利。
Objective Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real-world experiences comparing these strategies have not been well studied. Methods We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics-naive or biologics-exposed status of study participants. Results Patients eligible for analysis in this study included biologics-naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics-exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93-98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63-2.88] in the biologics-naive group; adjusted HR of 1.51 [95% confidence interval 1.06-2.15] in the biologics-exposed group). At 6 months, the proportion of biologics-naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (-9.3 units versus -5.5 [95% confidence interval -1.5, -6.1]). Corresponding results in the biologics-exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. Conclusion Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.