Department of Medicine, Birmingham VA Medical Center, Birmingham, AL, USA.
Department of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Cochrane Database Syst Rev. 2021 Feb 25;2(2):CD010668. doi: 10.1002/14651858.CD010668.pub2.
Belimumab, the first biologic approved for the treatment of systemic lupus erythematosus (SLE), has been shown to reduce autoantibody levels in people with SLE and help control disease activity.
To assess the benefits and harms of belimumab (alone or in combination) in systematic lupus erythematosus.
An Information Specialist carried out the searches of CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, the World Health Organization (WHO) International Clinical Trials Registry Platform, and clinicaltrials.gov from inception to 25 September 2019. There were no language or date restrictions.
We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of belimumab (alone or in combination) compared to placebo/control treatment (immunosuppressive drugs, such as azathioprine, cyclosporine, mycophenolate mofetil or another biologic), in adults with SLE.
We used standard methodologic procedures expected by Cochrane.
Six RCTs (2917 participants) qualified for quantitative analyses. All included studies were multicenter, international or US-based. The age range of the included participants was 22 to 80 years; most were women; and study duration ranged from 84 days to 76 weeks. The risk of bias was generally low except for attrition bias, which was high in 67% of studies. Compared to placebo, more participants on belimumab 10 mg/kg (Food and Drug Administration (FDA)-approved dose) showed at least a 4-point improvement (reduction) in Safety of Estrogen in Lupus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, a validated SLE disease activity index: (risk ratio (RR) 1.33, 95% confidence interval (CI) 1.22 to 1.45; 829/1589 in belimumab group and 424/1077 in placebo; I= 0%; 4 RCTs; high-certainty evidence). Change in health-related quality of life (HRQOL), assessed by Short Form-36 Physical Component Summary score improvement (range 0 to 100), showed there was probably little or no difference between groups (mean difference 1.6 points, 95% CI 0.30 to 2.90; 401 in belimumab group and 400 in placebo; I= 0%; 2 RCTs; moderate-certainty evidence). The belimumab 10 mg/kg group showed greater improvement in glucocorticoid dose, with a higher proportion of participants reducing their dose by at least 50% compared to placebo (RR 1.59, 95% CI 1.17 to 2.15; 81/269 in belimumab group and 52/268 in placebo; I= 0%; 2 RCTs; high-certainty evidence). The proportion of participants experiencing harm may not differ meaningfully between the belimumab 10 mg/kg and placebo groups: one or more serious adverse event (RR 0.87, 95% CI: 0.68 to 1.11; 238/1700 in belimumab group and 199/1190 in placebo; I= 48%; 5 RCTs; low-certainty evidence; ); one or more serious infection (RR 1.01, 95% CI: 0.66 to 1.54; 44/1230 in belimumab group and 40/955 in placebo; I= 0%; 4 RCTs; moderate-certainty evidence); and withdrawals due to adverse events (RR 0.82, 95% CI: 0.63 to 1.07; 113/1700 in belimumab group and 94/1190 in placebo; I= 0%; 5 RCTs; moderate-certainty evidence). Mortality was rare, and may not differ between belimumab 10 mg/kg and placebo (Peto odds ratio 1.15, 95% CI 0.41 to 3.25; 9/1714 in belimumab group and 6/1203 in placebo; I= 4%; 6 RCTs; low-certainty evidence).
AUTHORS' CONCLUSIONS: The six studies that provided evidence for benefits and harms of belimumab were well-designed, high-quality RCTs. At the FDA-approved dose of 10 mg/kg, based on moderate to high-certainty data, belimumab was probably associated with a clinically meaningful efficacy benefit compared to placebo in participants with SLE at 52 weeks. Evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence. More data are needed for the longer-term efficacy of belimumab.
贝鲁单抗是首个获批用于治疗系统性红斑狼疮（SLE）的生物制剂，已被证明可以降低 SLE 患者的自身抗体水平，并有助于控制疾病活动。
评估贝鲁单抗（单独或联合用药）治疗系统性红斑狼疮的疗效和安全性。
信息专家对 CENTRAL、MEDLINE、Embase、CINAHL、Web of Science、世界卫生组织（WHO）国际临床试验注册平台和 clinicaltrials.gov 进行了检索，检索时间截至 2019 年 9 月 25 日，未设语言和日期限制。
我们纳入了贝鲁单抗（单独或联合用药）与安慰剂/对照治疗（免疫抑制剂，如硫唑嘌呤、环孢素、霉酚酸酯或其他生物制剂）比较的随机对照试验（RCT）或对照临床试验（CCT），研究对象为成人 SLE 患者。
我们使用了 Cochrane 预期的标准方法学程序。
六项 RCT（2917 名参与者）符合定量分析的标准。所有纳入的研究均为多中心、国际或美国的研究。纳入参与者的年龄范围为 22 至 80 岁；大多数为女性；研究持续时间从 84 天到 76 周不等。除了失访偏倚较高（67%的研究存在该偏倚）外，纳入研究的偏倚风险通常较低。与安慰剂相比，更多接受贝鲁单抗 10mg/kg（FDA 批准剂量）治疗的患者在安全性评估的雌激素在狼疮中的评估（SELENA）-系统性红斑狼疮疾病活动指数（SLEDAI）评分中至少有 4 分的改善（减少）：（风险比（RR）1.33，95%置信区间（CI）1.22 至 1.45；贝鲁单抗组 829/1589 例，安慰剂组 424/1077 例；I=0%；4 项 RCT；高质量证据）。健康相关生活质量（HRQOL）的变化，用简化 36 项健康调查量表的物理成分综合评分（范围 0 至 100）的改善来评估，显示两组之间可能差异较小或无差异（平均差值 1.6 分，95%CI 0.30 至 2.90；贝鲁单抗组 401 例，安慰剂组 400 例；I=0%；2 项 RCT；中等质量证据）。贝鲁单抗 10mg/kg 组的糖皮质激素剂量减少幅度更大，与安慰剂相比，更多的患者减少了至少 50%的剂量（RR 1.59，95%CI 1.17 至 2.15；贝鲁单抗组 81/269 例，安慰剂组 52/268 例；I=0%；2 项 RCT；高质量证据）。贝鲁单抗 10mg/kg 组和安慰剂组的不良事件发生率可能没有明显差异：一项或多项严重不良事件（RR 0.87，95%CI：0.68 至 1.11；贝鲁单抗组 238/1700 例，安慰剂组 199/1190 例；I=48%；5 项 RCT；低质量证据；）；一项或多项严重感染（RR 1.01，95%CI：0.66 至 1.54；贝鲁单抗组 44/1230 例，安慰剂组 40/955 例；I=0%；4 项 RCT；中等质量证据）；以及因不良事件而退出（RR 0.82，95%CI：0.63 至 1.07；贝鲁单抗组 113/1700 例，安慰剂组 94/1190 例；I=0%；5 项 RCT；中等质量证据）。死亡率较低，贝鲁单抗 10mg/kg 组和安慰剂组之间可能没有差异（Peto 比值比 1.15，95%CI 0.41 至 3.25；贝鲁单抗组 9/1714 例，安慰剂组 6/1203 例；I=4%；6 项 RCT；低质量证据）。
提供贝鲁单抗疗效和安全性证据的六项研究设计良好，质量较高。在 FDA 批准的 10mg/kg 剂量下，基于中到高度确定性数据，与安慰剂相比，贝鲁单抗在 52 周时可能与 SLE 患者的临床疗效获益相关。与安全性相关的证据尚不确定，且主要为中到低质量证据。需要更多数据来评估贝鲁单抗的长期疗效。
