From the Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (UMRS 1136), GRC-UPMC 08 (EEMOIS); Rheumatology Department, Hôpital Pitié Salpêtrière, AP-HP, Paris, France; Stanford University, Palo Alto, California, USA; Sanofi, Guildford, UK; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA; Sanofi, Paris, France; Sanofi, Bridgewater, New Jersey, USA.
L. Gossec, MD, PhD, Sorbonne Université and Rheumatology Department, Hôpital Pitié Salpêtrière, Institut Pierre Louis d'Epidémiologie et de Santé Publique (UMRS 1136), GRC-UPMC 08 (EEMOIS); V. Strand, MD, Stanford University; C. Proudfoot, PhD, Novartis; C.I. Chen, MPH, Regeneron Pharmaceuticals Inc.; S. Guillonneau, MSc, Sanofi; T. Kimura, MSc, Regeneron Pharmaceuticals Inc.; H. van Hoogstraten, MD/PhD, Sanofi; E. Mangan, PhD, Regeneron Pharmaceuticals Inc.; M. Reaney, MSc, formerly of Sanofi.
J Rheumatol. 2019 Oct;46(10):1259-1267. doi: 10.3899/jrheum.180904. Epub 2019 Mar 15.
We evaluated the effect of sarilumab on patient-perceived impact of rheumatoid arthritis (RA) using the 7-domain RA Impact of Disease (RAID) scale.
Two phase III, randomized, controlled trials of sarilumab in patients with active, longstanding RA were analyzed: (1) sarilumab 150 mg and 200 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARD) versus placebo + csDMARD [TARGET (NCT01709578)]; and (2) sarilumab 200 mg versus adalimumab (ADA) 40 mg monotherapy [MONARCH (NCT02332590)]. Least-squares mean (LSM) differences in RAID total score (range 0-10) and 7 key RA symptoms, including pain and fatigue (baseline to Weeks 12 and 24), were compared. "Responders" by RAID total score were defined by improvements from baseline ≥ minimal clinically important difference (MCID), and ≥ patient-acceptable symptom-state (PASS) at endpoint.
Sarilumab 150 mg and 200 mg + csDMARD were nominally superior (p < 0.05) versus placebo + csDMARD and 200 mg sarilumab versus ADA 40 mg in LSM differences for RAID total score at weeks 12 (-0.93 and -1.13; -0.49, respectively) and 24 (-0.75 and -1.01; -0.78), and all effects of RA (except functional impairment in MONARCH Week 12). Effects were greater in physical domains (e.g., pain) than mental domains (e.g., emotional well-being). More patients receiving sarilumab versus placebo or ADA reported improvements ≥ MCID and PASS in total RAID scores at both assessments.
Based on the RAID, sarilumab + csDMARD or as monotherapy reduced the effect of RA on patients' lives to a greater extent than placebo + csDMARD or ADA monotherapy. (ClinicalTrials.gov: NCT01709578 and NCT02332590).
我们使用疾病影响评估（RAID）7 域量表评估了 sarilumab 对类风湿关节炎（RA）患者感知疾病影响的效果。
对两项 sarilumab 治疗活动性、长期 RA 患者的 III 期随机对照试验进行了分析：（1）sarilumab 150mg 和 200mg 每 2 周 1 次联合常规合成改善病情抗风湿药物（csDMARD）+与安慰剂+csDMARD[靶向（NCT01709578）]；（2）sarilumab 200mg 与阿达木单抗（ADA）40mg 单药治疗[MONARCH（NCT02332590）]。比较 RAID 总分（0-10 分）和 7 个关键 RA 症状（包括疼痛和疲劳）的最小二乘均数（LSM）差异（基线至 12 周和 24 周）。根据 RAID 总分改善≥最小临床重要差异（MCID）和终点时≥患者可接受的症状状态（PASS），定义为“应答者”。
sarilumab 150mg 和 200mg+csDMARD 与安慰剂+csDMARD 和 200mg sarilumab 与 ADA 40mg 相比，在 12 周（-0.93 和-1.13；分别为-0.49）和 24 周（-0.75 和-1.01；分别为-0.78）时，RAID 总分的 LSM 差异有统计学意义（均为 P＜0.05），且 RA 的所有影响（MONARCH 第 12 周的功能障碍除外）均有统计学意义。在身体领域（如疼痛）的效果大于在心理领域（如情绪健康）的效果。与安慰剂或 ADA 相比，更多接受 sarilumab 治疗的患者报告称在这两项评估中，RAID 总分改善≥MCID 和 PASS。
根据 RAID，sarilumab+csDMARD 或单药治疗较安慰剂+csDMARD 或 ADA 单药治疗能更大程度地减轻 RA 对患者生活的影响。（临床试验.gov：NCT01709578 和 NCT02332590）
