Huffstutter Joseph E, Kafka Shelly, Brent Lawrence H, Matucci-Cerinic Marco, Tang Kezhen L, Chevrier Marc, Sprabery Trev, DeHoratius Raphael J
a Internal Medicine, Rheumatology , Arthritis Associates PLLC , Hixson , TN , USA.
b Mountain State Clinical Research , Clarksburg , WV , USA.
Curr Med Res Opin. 2017 Apr;33(4):657-666. doi: 10.1080/03007995.2016.1277195. Epub 2017 Jan 25.
Evaluate the efficacy and safety of subcutaneous (SC) golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite etanercept + MTX or adalimumab + MTX therapy and evaluate whether intravenous (IV) golimumab could rescue patients who were nonresponders to SC golimumab.
In this multicenter, assessor-blinded, active-switch study of patients with RA (n = 433) with inadequate response to etanercept or adalimumab + MTX, patients continued MTX and received open-label SC golimumab 50 mg every 4 weeks through week 12. DAS28-ESR good responders at week 16 continued open-label SC golimumab through week 52 (Group 1); nonresponders were randomized to double-blind golimumab SC 50 mg (Group 2-SC) or IV 2 mg/kg (Group 2-IV). Week 14 ACR20 was the primary endpoint; assessments continued through week 52 and for patients in the voluntary long-term extension through week 76. A major secondary endpoint was the proportions of patients with ACR20 response at week 52 relative to week 16 in Group 2-SC and Group 2-IV.
At week 14, 34.9% (p < 0.001) achieved an ACR20. At week 52, patients in Group 1 (n = 75) achieved an ACR20 (62.7%). In Groups 2-SC (n = 91) and 2-IV (n = 184), 13.2% and 9.2% had an ACR20 at week 52 relative to week 16, with no significant difference between the randomized groups; 42.9% and 47.8% achieved DAS28-ESR response relative to week 0. Through week 16, 4.6% of patients had a serious adverse event. No differences in the rates or types of adverse events were observed between SC and IV golimumab from weeks 16 to 52. The trial limitations included a higher than expected discontinuation rate as a result of a programming error.
SC golimumab + MTX significantly suppressed disease activity in RA patients with inadequate response to etanercept and/or adalimumab + MTX. Patients randomized to Groups 2-SC and 2-IV had lower response rates than Group 1, with no difference between SC or IV mode of administration. The safety profile with IV golimumab was comparable to that established with SC golimumab.
NCT01004432, EudraCT 2009-010582-23.
评估皮下注射（SC）戈利木单抗联合甲氨蝶呤（MTX）用于尽管接受了依那西普联合MTX或阿达木单抗联合MTX治疗但仍患有活动性类风湿关节炎（RA）患者的疗效和安全性，并评估静脉注射（IV）戈利木单抗能否挽救对SC戈利木单抗无反应的患者。
在这项针对对依那西普或阿达木单抗联合MTX反应不佳的RA患者（n = 433）的多中心、评估者盲法、活性药物转换研究中，患者继续接受MTX治疗，并在第12周前每4周接受一次50 mg的开放标签SC戈利木单抗治疗。第16周达到疾病活动评分28-红细胞沉降率（DAS28-ESR）良好反应的患者继续接受开放标签SC戈利木单抗治疗至第52周（第1组）；无反应者被随机分为双盲的50 mg SC戈利木单抗组（第2-SC组）或2 mg/kg IV戈利木单抗组（第2-IV组）。第14周美国风湿病学会20%改善标准（ACR20）是主要终点；评估持续至第52周，对于自愿长期延长期的患者评估至第76周。一个主要次要终点是第2-SC组和第2-IV组中第52周相对于第16周达到ACR20反应的患者比例。
在第14周，34.9%（p < 0.001）的患者达到ACR20。在第52周，第1组（n = 75）的患者达到ACR20（62.7%）。在第2-SC组（n = 91）和第2-IV组（n = 184）中，相对于第16周，第52周分别有13.2%和9.2%的患者达到ACR20，随机分组的两组之间无显著差异；相对于第0周，分别有42.9%和47.8%的患者达到DAS28-ESR反应。至第16周，4.6%的患者发生严重不良事件。在第16周至第52周期间，SC和IV戈利木单抗在不良事件的发生率或类型上未观察到差异。试验的局限性包括由于程序错误导致停药率高于预期。
SC戈利木单抗联合MTX可显著抑制对依那西普和/或阿达木单抗联合MTX反应不佳的RA患者的疾病活动。随机分为第2-SC组和第2-IV组患者的反应率低于第1组，SC或IV给药方式之间无差异。IV戈利木单抗的安全性与SC戈利木单抗相当。
NCT01004432，欧洲药品管理局临床试验注册号2009-0105
