University of Alabama at Birmingham.
Corrona Research Foundation, Albany, New York.
Arthritis Care Res (Hoboken). 2021 Aug;73(8):1114-1124. doi: 10.1002/acr.24253.
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.
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.
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.
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.
虽然随机对照试验表明，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，但对这些策略的真实世界经验尚未进行充分研究。
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 联合疗法的临床疗效和停药效果。采用倾向评分匹配将患者按 1:3 的比例匹配，以调整治疗组之间的不平衡，根据研究参与者的生物制剂初治或暴露情况进行分层。
本研究分析中符合条件的患者包括生物制剂初治 RA 患者（接受 TNFi/MTX 联合治疗的 3926 例和接受 MTX/SSZ/HCQ 三联治疗的 262 例）和生物制剂暴露 RA 患者（接受 TNFi/MTX 联合治疗的 3365 例和接受 MTX/SSZ/HCQ 三联治疗的 130 例）。在进行倾向评分匹配之前，治疗组之间存在许多不平衡的因素，三联疗法患者通常年龄较大，RA 病程和 RA 疾病活动度较长，且更可能有恶性肿瘤和其他合并症的病史。匹配后，几乎所有（93-98%）的三联疗法患者都可以与 TNFi/MTX 治疗患者匹配，队列特征通常平衡良好。与 TNFi/MTX 治疗患者相比，三联疗法患者停药的比例更高（生物制剂初治组调整后的危险比[HR]为 2.17[95%置信区间 1.63-2.88]；生物制剂暴露组调整后的 HR 为 1.51[95%置信区间 1.06-2.15]）。在 6 个月时，TNFi/MTX 治疗组达到低疾病活动度的生物制剂初治患者比例显著高于三联疗法组（TNFi/MTX 治疗患者为 49.2%，三联疗法患者为 33.3%），临床疾病活动指数评分的平均变化也更大（-9.3 单位，-5.5[95%置信区间-1.5，-6.1]）。在生物制剂暴露患者中，相应的结果数值上倾向于 TNFi/MTX 治疗，但未达到统计学意义。
在美国，很少有患者接受 MTX/SSZ/HCQ 的三联疗法。在本研究中，与 TNFi/MTX 治疗患者相比，三联疗法患者的药物持久性和临床疗效结果较差。
