文摘
摘要目的:比较疗效和安全性ozanimod和干扰素(IFN)β-1a复发多发性硬化症(RMS)。
背景:Ozanimod,口服,每日一次免疫调制剂,有选择地目标鞘氨醇1-phosphate受体1和5。
设计/方法:阳光(NCT02294058)评估ozanimod HCl 1或0.5毫克剂量递增(7天)与30μg每周肌肉注射干扰素β-1a≥12个月。主要终点:年复发率(ARR)在治疗期间;二次端点:T2和钆增强(GdE)病变(12个月),残疾进展(合并与另一个3期研究),脑容量损失(BVL;基线至12个月)。
结果:基线特征(1346名患者)是类似的武器。Ozanimod 1毫克(0.181;p < 0.0001)和0.5毫克(0.241;p = 0.0013)减少调整ARR对干扰素β-1a (0.350)。调整意味着每个扫描的新/扩大T2病灶数减少48%,ozanimod 1毫克(1.465;0.5毫克p < 0.0001)和25% (2.139;p = 0.0032)和干扰素β-1a (2.836)。调整意味着GdE病变数量减少63% ozanimod 1毫克(0.160;0.5毫克p < 0.0001)和34% (0.287;p = 0.0182)和干扰素β-1a (0.433)。 Confirmed 3-month pooled disability progression was low across all treatment groups (0.102, 0.080, 0.099, respectively). Ozanimod 1 mg significantly slowed whole BVL versus IFN β-1a (32.5%, p<0.0001), with more modest slowing for ozanimod 0.5 mg (12.3%, p=0.0615). Both ozanimod doses significantly slowed cortical gray matter volume loss (1 mg, 83.8%; 0.5 mg, 61.4%; both p<0.0001), and thalamic volume loss (1 mg, 38.5% [p<0.0001]; 0.5 mg, 34.3% [p=0.0001]). More IFN β-1a–treated than ozanimod-treated patients experienced adverse events (AEs). Serious AE incidences including infections were balanced across arms. No first-dose, clinically significant heart rate reduction, or second degree or higher atrioventricular block, were reported.
结论:两ozanimod剂量显示优势干扰素β-1a加勒比海盗和MRI端点,包括BVL。这些疗效和安全性/耐受性结果表明口服ozanimod在RMS有利其配置文件。
研究支持:Celgene公司
披露:Comi博士没有披露。阿诺德博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Acorda或其他活动,生原体,f .罗氏公司有限公司MedDay,落实的三菱、诺华,Receptos / Celgene公司,赛诺菲-安万特。阿诺德博士已经收到赔偿服务NeuroRx董事会的研究。克里族博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Abbvie或其他活动,生原体,EMD Serono, GeNEuro,诺华,赛诺菲安万特Genzyme。克里族已经收到Acorda研究支持博士霍夫曼罗氏,落实的诺华,Receptos和梯瓦。卡珀斯博士收到拜耳医疗药品、研究支持生原体,f .罗氏公司有限公司基因泰克,诺华,研究经费:欧盟、瑞士罗氏公司研究基金会、瑞士多发性硬化症协会和国家研究基金会。Selmaj博士已经收到个人赔偿咨询、担任科学顾问委员会说,与生原体或其他活动,Celgene公司,诺华,默克,罗氏。酒吧或者博士没有披露。斯坦曼博士已经收到个人赔偿咨询、担任科学顾问委员会说,Celgene公司或其他活动,默克公司Coherus Atreca。斯坦曼博士已经收到赔偿服务Atreca董事会,Tolerion。 Dr. Steinman has received royalty, license fees, or contractual rights payments from Tolerion. Dr. Steinman has received research support from Coherus, Celgene. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, GeNeuro, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Octapharma, Opexa Therapeutics, Teva Pharmaceuticals, MedImmune, Bayer HealthCare, Forward Pharma, and Roche. Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi and Teva Pharmaceutical. Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme and Teva. Dr. Sheffield has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Raghupathi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Adams, Celgene.
