Faculty of Medicine, Tanta University, Tanta, Egypt.
Cardiology Department, The Lundquist Institute, Torrance, CA, USA.
Clin Rheumatol. 2023 Jun;42(6):1503-1520. doi: 10.1007/s10067-023-06519-6. Epub 2023 Feb 16.
Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022358082. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58], P = 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79], P = 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48], P = 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: - 0.28 with 95% CI [- 0.38, - 0.18], P = 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs. Key Points • OKZ is effective especially with methotrexate in RA patients.
奥洛昔单抗（OKZ）是一种新型的白细胞介素 6（IL-6）抑制剂，可直接靶向 IL-6，而非其受体。我们旨在评估 OKZ 治疗类风湿关节炎（RA）患者的疗效和安全性，并探讨最佳治疗方案。对 WOS、CENTRAL、SCOPUS、EMBASE 和 PubMed 中的随机对照试验（RCT）进行系统评价、成对比较和网络荟萃分析，截至 2022 年 8 月 31 日。我们分别使用风险比（RR）和均数差值（MD）来表示二分类和连续性结局，并给出相应的 95%置信区间（CI）。我们将研究方案在 PROSPERO 注册，编号为 CRD42022358082。纳入了 5 项 RCT，共 2277 例患者。与安慰剂相比，OKZ 能显著改善美国风湿病学会（ACR）20 标准（RR：1.97，95%CI [1.49, 2.58]，P=0.00001）、ACR50（RR：3.83，95%CI [2.13, 6.87]，P=0.00001）、ACR70（RR：3.83，95%CI [2.13, 6.87]，P=0.00001）、基于 C 反应蛋白的 28 个关节疾病活动度评分（DAS28-CRP）（RR：3.91，95%CI [2.65, 5.79]，P=0.00001）、临床疾病活动指数（CDAI）（RR：2.80，95%CI [1.43, 5.48]，P=0.003）和健康评估问卷残疾指数（HAQ-DI）（MD：-0.28，95%CI [-0.38, -0.18]，P=0.00001）。然而，与安慰剂相比，OKZ 也与更高的任何不良事件（AE）发生率（RR：1.15，95%CI [1.06, 1.25]，P=0.0005）和导致停药的 AE（RR：1.86，95%CI [1.05, 3.29]，P=0.03）相关。对于肿瘤坏死因子抑制剂治疗反应不佳的 RA 患者，在联合甲氨蝶呤治疗时，OKZ 有效且安全性可接受；然而，仍需要更多的大规模 RCT 来探究其最佳剂量、长期疗效以及与已确立的生物 DMARD 相比的疗效。主要结论：OKZ 联合甲氨蝶呤治疗对肿瘤坏死因子抑制剂治疗反应不佳的 RA 患者有效。
