Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
J Rheumatol. 2011 Dec;38(12):2572-80. doi: 10.3899/jrheum.110570. Epub 2011 Nov 15.
To evaluate the efficacy/safety of subcutaneous (SC) golimumab in patients with rheumatoid arthritis (RA) who previously received intravenous (IV) golimumab with or without methotrexate (MTX).
Adult patients with RA (n = 643) with persistent disease despite MTX (≥ 15 mg/wk for ≥ 3 months) were randomized to IV placebo + MTX (n = 129) or IV golimumab 2-4 mg/kg (± MTX) every 12 weeks (n = 514). Patients who completed the study through Week 48 could participate in the longterm extension (LTE), comprising open-label golimumab 50 mg SC every 4 weeks (± MTX) for 24 weeks (LTE-0 to LTE-24) followed by 16 weeks of safety followup (LTE-24 to LTE-40; MTX could be adjusted).
At Week 48, 28% (nominal p < 0.001 vs placebo), 11%, and 8% of patients who received IV golimumab + MTX, golimumab alone, and placebo + MTX, respectively, achieved ≥ 50% improvement in the American College of Rheumatology response criteria (ACR50). Among the 505 patients who entered the LTE and were still participating, the proportion of patients treated with golimumab 50 mg SC (± MTX) achieving an ACR50 response increased to 44% at both LTE-14 and LTE-24. ACR20, ACR70, and 28-joint Disease Activity Score using C-reactive protein exhibited similar response patterns as ACR50. Infections were the most commonly reported adverse events through the end of IV golimumab dosing (37% placebo + MTX, 45% golimumab, 51% golimumab + MTX) and with SC golimumab from LTE-0 through LTE-40 (35% golimumab, 36% golimumab + MTX). Concomitant MTX use yielded lower incidences of antibodies to SC golimumab and injection-related reactions.
Clinical improvements observed in golimumab-treated patients were sustained or improved in patients switched from IV (2-4 mg/kg ± MTX) to open-label SC (50 mg ± MTX) golimumab. Both IV and SC golimumab demonstrated acceptable safety profiles (Clinicaltrials.gov NCT00361335).
评估先前接受过静脉注射（IV）戈利木单抗联合或不联合甲氨蝶呤（MTX）治疗的类风湿关节炎（RA）患者皮下（SC）戈利木单抗的疗效/安全性。
纳入 643 例 MTX 治疗效果不佳（≥ 15mg/周，持续 3 个月以上）的 RA 成年患者，随机分为 IV 安慰剂+MTX（n=129）或 IV 戈利木单抗 2-4mg/kg（± MTX），每 12 周 1 次（n=514）。完成第 48 周研究的患者可参加长期扩展（LTE），包括皮下戈利木单抗 50mg/4 周（± MTX）治疗 24 周（LTE-0 至 LTE-24），随后进行 16 周安全性随访（LTE-24 至 LTE-40；可调整 MTX）。
第 48 周时，分别有 28%（名义 p<0.001 对比安慰剂）、11%和 8%接受 IV 戈利木单抗+MTX、单独戈利木单抗和安慰剂+MTX治疗的患者达到美国风湿病学会（ACR）50 缓解标准的改善≥50%。在进入 LTE 且仍在参与的 505 例患者中，接受皮下戈利木单抗 50mg（± MTX）治疗的患者比例增加至 LTE-14 和 LTE-24 时的 44%。ACR20、ACR70 和 28 关节疾病活动评分（使用 C 反应蛋白）也呈现出与 ACR50 相似的反应模式。治疗结束时，最常报告的不良事件为感染（安慰剂+MTX 组 37%、戈利木单抗组 45%、戈利木单抗+MTX 组 51%）和 LTE-0 至 LTE-40 时的皮下戈利木单抗（35%戈利木单抗、36%戈利木单抗+MTX）。同时使用 MTX 可降低针对 SC 戈利木单抗的抗体发生率和注射相关反应发生率。
从 IV（2-4mg/kg±MTX）转换为开放标签 SC（50mg±MTX）戈利木单抗治疗的患者，其戈利木单抗治疗患者的临床改善持续或改善。IV 和 SC 戈利木单抗均具有可接受的安全性特征（Clinicaltrials.gov NCT00361335）。
