背景:系统性硬化症(SSc)是一种罕见的,复杂,结缔组织疾病。间质性肺病(ILD)在SSc中很常见,发生在35-52%的患者中,占死亡率的20-40%。治疗选择的演变导致对如何管理这种情况缺乏共识。这项Delphi研究旨在根据专家医师对筛查的见解制定共识建议,programming,治疗标准,监测反应,以及抗纤维化药物和免疫抑制剂在SSc-ILD患者中的最新治疗进展。
方法:由具有SSc-ILD患者管理专业知识的肺科医师(n=13)和风湿病医师(n=12)完成了改良的Delphi过程。小组成员在李克特量表上对每个陈述的协议进行评分,从-5(完全不同意)到+5(完全同意)。共识被预定义为平均李克特量表评分≤-2.5或≥+2.5,标准偏差不超过零。
结果:小组成员建议通过胸部听诊对所有SSc患者进行ILD筛查,肺具有一氧化碳扩散能力的肺活量测定,高分辨率计算机断层扫描(HRCT),和/或自身抗体测试。治疗决定受基线和肺功能检查变化的影响,HRCT上ILD的程度,呼吸困难的持续时间和程度,肺动脉高压的存在,和回流的潜在贡献。治疗成功定义为ILD的体征或症状和功能状态的稳定或改善。霉酚酸酯被确定为选择的初始治疗。专家认为尼达尼布是进行性纤维化ILD患者的治疗选择,尽管有免疫抑制治疗或患者禁忌/不能耐受免疫治疗。在初次就诊的晚期疾病患者中,可考虑同时使用尼达尼布与MMF/环磷酰胺。侵略性ILD,或重大疾病进展。尽管在使用托珠单抗方面取得了有限的共识,专家认为这是早期SSc和ILD患者急性期反应物升高的治疗选择.
结论:这项改良的Delphi研究为在现实环境中处理SSc-ILD患者提供了共识建议。这项研究的发现提供了一种管理算法,该算法将有助于治疗SSc-ILD患者,并解决了显着的未满足需求。
BACKGROUND: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35-52% of patients and accounting for 20-40% of mortality. Evolution of therapeutic options has resulted in a lack of
consensus on how to manage this condition. This Delphi study was initiated to develop
consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD.
METHODS: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from - 5 (complete disagreement) to + 5 (complete agreement).
Consensus was predefined as a mean Likert scale score of ≤ - 2.5 or ≥ + 2.5 with a standard deviation not crossing zero.
RESULTS: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited
consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants.
CONCLUSIONS: This modified Delphi study generated
consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.