期刊论文详细信息
Arthritis Research & Therapy
High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab
Susan H. Boklage1  Anita Boyapati2  Toshio Kimura2  Jérôme Msihid3  Florence Joly3  Vibeke Strand4 
[1] Formerly, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA;Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA;Sanofi, 1 Avenue Pierre Brossolette, 91385, Chilly-Mazarin, France;Stanford University, Palo Alto, CA, USA;
关键词: Rheumatoid arthritis;    Interleukin-6;    Sarilumab;    Morning stiffness;    Fatigue;    Physical function;    Pain;    Biomarkers;    Health-related quality of life;    Adalimumab;   
DOI  :  10.1186/s13075-020-02344-3
来源: Springer
PDF
【 摘 要 】

BackgroundIncreased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) versus adalimumab, a tumor necrosis factor α inhibitor, both approved for treatment of active RA.MethodsBaseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6–7.1 pg/mL), medium (7.2–39.5 pg/mL), and high (39.6–692.3 pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID).ResultsAt baseline, patients with high versus medium or low IL-6 levels (n = 100, respectively) reported worse (nominal p < 0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p < 0.05). PCS improvements ≥MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p < 0.05). Adverse events between IL-6 tertiles were similar.ConclusionsPatients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade.Trial registrationNCT02332590. Registered on 5 January 2015

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202104272007951ZK.pdf 939KB PDF download
  文献评价指标  
  下载次数:5次 浏览次数:10次