Pestaña-Fernández Melani, Rubio-Rivas Manuel, Tolosa-Vilella Carles, Guillén-Del-Castillo Alfredo, Freire Mayka, Vargas-Hitos Jose Antonio, Todolí-Parra Jose Antonio, Rodríguez-Carballeira Mónica, Marín-Ballvé Adela, Espinosa Gerard, Colunga-Argüelles Dolores, Ortego-Centeno Norberto, Trapiella-Martínez Luis, Carbonell-Muñoz Cristina, Pla-Salas Xavier, Perales-Fraile Isabel, Corbella Xavier, Fonollosa-Pla Vicent, Simeón-Aznar Carmen Pilar
J Rheumatol. 2020 Jan;47(1):89-98. doi: 10.3899/jrheum.180595. Epub 2019 Feb 15.
Monotherapy is an option as first-line therapy for pulmonary arterial hypertension (PAH). However, combination therapy is a beneficial alternative. Our objective was to evaluate the efficacy of monotherapy versus combination therapy in patients with systemic sclerosis (SSc)-associated PAH.
All patients with SSc-associated PAH from the Spanish Scleroderma Registry (RESCLE) were reviewed. Patients were split into 3 groups: monotherapy versus sequential combination versus upfront combination therapy. The primary endpoint was death from any cause at 1, 3, and 5 years from PAH diagnosis.
Seventy-six patients (4.2%) out of 1817 had SSc-related PAH. Thirty-four patients (45%) were receiving monotherapy [endothelin receptor antagonist (n = 22; 29%) or phosphodiesterase-5 inhibitors (n = 12; 16%)], 25 (33%) sequential combination, and 17 (22%) upfront combination therapy. A lower forced vital capacity/DLCO in the sequential combination group was reported (2.9 ± 1.1 vs 1.8 ± 0.4 vs 2.3 ± 0.8; p = 0.085) and also a higher mean pulmonary arterial pressure in combination groups (37.2 ± 8.7 mmHg vs 40.8 ± 8.8 vs 46 ± 15.9; p = 0.026) at baseline. Treatment regimen (p = 0.017) and functional class (p = 0.007) were found to be independent predictors of mortality. Sequential combination therapy was found to be an independent protective factor (HR 0.11, 95% CI 0.03-0.51; p = 0.004), while upfront combination therapy showed a trend (HR 0.68, 95% CI 0.23-1.97; p = 0.476). Survival from PAH diagnosis among monotherapy, sequential, and upfront combination groups was 78% versus 95.8% versus 94.1% at 1 year, 40.7% versus 81.5% versus 51.8% at 3 years, and 31.6% versus 56.5% versus 34.5% at 5 years (p = 0.007), respectively. Side effects were not significantly different among groups.
Combination sequential therapy improved survival in our cohort.
单药治疗是肺动脉高压（PAH）一线治疗的一种选择。然而，联合治疗是一种有益的替代方案。我们的目的是评估单药治疗与联合治疗在系统性硬化症（SSc）相关PAH患者中的疗效。
对西班牙硬皮病注册中心（RESCLE）中所有SSc相关PAH患者进行了回顾。患者被分为3组：单药治疗组、序贯联合治疗组和初始联合治疗组。主要终点是PAH诊断后1年、3年和5年的任何原因导致的死亡。
1817例患者中有76例（4.2%）患有SSc相关PAH。34例患者（45%）接受单药治疗[内皮素受体拮抗剂（n = 22；29%）或磷酸二酯酶-5抑制剂（n = 12；16%）]，25例（33%）接受序贯联合治疗，17例（22%）接受初始联合治疗。序贯联合治疗组的用力肺活量/一氧化碳弥散量较低（分别为2.9±1.1、1.8±0.4和2.3±0.8；p = 0.085），联合治疗组基线时平均肺动脉压也较高（分别为37.2±8.7 mmHg、40.8±8.8和46±15.9；p = 0.026）。治疗方案（p = 0.017）和功能分级（p = 0.007）是死亡率的独立预测因素。序贯联合治疗是一个独立的保护因素（风险比0.11，95%置信区间0.03 - 0.51；p = 0.004），而初始联合治疗显示出一种趋势（风险比0.68，95%置信区间0.23 - 1.97；p = 0.476）。单药治疗组、序贯联合治疗组和初始联合治疗组从PAH诊断开始的1年生存率分别为78%、95.8%和94.1%，3年生存率分别为40.7%、81.5%和51.8%，5年生存率分别为31.6%、56.5%和34.5%（p = 0.007）。各组间副作用无显著差异。
序贯联合治疗提高了我们队列中的生存率。
