Navarro F, Martinez-Sesmero J M, Balsa A, Peral C, Montoro M, Valderrama M, Gómez S, de Andrés-Nogales F, Casado M A, Oyagüez Itziar
Rheumatology Deparment Hospital Quirón Salud Infanta Luisa, Seville, Spain.
Hospital Pharmacy, Hospital Universitario Clínico San Carlos, Madrid, Spain.
Clin Rheumatol. 2020 Oct;39(10):2919-2930. doi: 10.1007/s10067-020-05087-3. Epub 2020 Apr 17.
To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population).
A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management.
In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option.
Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.
评估在传统合成抗风湿药物(csDMARDs)治疗失败后的中重度类风湿关节炎(RA)患者(csDMARD-IR人群)以及先前接受甲氨蝶呤(MTX)治疗但对任何肿瘤坏死因子抑制剂二线治疗反应不足的患者(TNFi-IR人群)中,含托法替布的治疗方案与仅含标准生物疗法的方案相比的成本效益。
一个患者水平的微观模拟模型从西班牙公共国民健康服务体系的角度估计了以托法替布(每日两次,每次5mg)起始随后进行生物疗法的治疗方案与仅生物治疗方案的终身成本和质量调整生命年(QALY)。考虑了与MTX的联合治疗。模型参数包括人口统计学和临床输入(初始健康评估问卷[HAQ]评分以及对短期和长期治疗的临床反应)。通过混合治疗比较使用HAQ评分变化以及长期扩展(LTE)试验的数据来衡量疗效。严重不良事件(SAE)数据来自文献。总成本估计(€,2018年)包括药物采购、胃肠外给药、疾病进展和SAE管理。
在csDMARD-IR人群中,与不含托法替布的相应方案相比,以托法替布起始的方案被证明是占优选择(更多QALY且成本更低)。在TNFi-IR人群中,托法替布+MTX一线治疗后序贯皮下注射阿巴西普+MTX➔利妥昔单抗+MTX➔赛妥珠单抗+MTX被证明比皮下注射托珠单抗+MTX➔皮下注射阿巴西普+MTX➔利妥昔单抗+MTX➔赛妥珠单抗+MTX更具优势;托法替布+MTX➔皮下注射托珠单抗+MTX➔皮下注射阿巴西普+MTX➔利妥昔单抗+MTX与皮下注射托珠单抗+MTX➔皮下注射阿巴西普+MTX➔利妥昔单抗+MTX➔赛妥珠单抗+MTX相比效果较差,但仍是一种节省成本的选择。
在csDMARDs治疗失败后的中重度RA患者中,纳入托法替布似乎是一种占优策略。在中重度TNFi-IR RA患者中,托法替布作为初始三线治疗被证明是一种节省成本的策略(每放弃一个QALY节省€-337,489)。要点 • 类风湿关节炎(RA)的治疗方法包括患者一生中多种疗法的序贯使用。 • 与仅含生物药物的方案相比,以托法替布起始随后使用生物药物的治疗方案在csDMARDs-IR人群中提供了更高的健康效益。 • 在csDMARD-IR和TNFi-IR RA人群中,以托法替布起始治疗对西班牙国家卫生系统而言与更低的治疗成本相关。