在系统性红斑狼疮患者中使用贝利木单抗的长期安全性和疗效：美国一项 76 周 III 期母研究的延续。
Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States.
机构信息
Northwell Health, Great Neck, New York.
Cedars-Sinai Medical Center, University of California, Los Angeles.
出版信息
Arthritis Rheumatol. 2018 Jun;70(6):868-877. doi: 10.1002/art.40439. Epub 2018 Apr 25.
OBJECTIVE
We undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76-week trial (ClinicalTrials.gov identifier: NCT00410384).
METHODS
Patients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long-term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels.
RESULTS
Of 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment-related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4-point reduction in the SELENA-SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was -83.2%.
CONCLUSION
These long-term exposure results confirm the previously observed safety and efficacy profiles of belimumab in patients with SLE.
目的
我们开展了这项美国多中心延续研究（GSK 研究 BEL112233；临床试验.gov 标识符：NCT00724867），以评估贝鲁单抗在系统性红斑狼疮（SLE）患者中的长期安全性和疗效，这些患者完成了 Study of Belimumab in Subjects with SLE 76 周试验（临床试验.gov 标识符：NCT00410384）。
方法
患者继续接受相同剂量的贝鲁单抗加标准治疗；先前接受安慰剂的患者接受 10mg/kg 贝鲁单抗。主要结局指标是贝鲁单抗的长期安全性（不良事件[AE]的频率和使用系统性红斑狼疮国际合作临床/美国风湿病学会损害指数[SDI]评估的损害，每 48 周[1 年研究]评估一次）。其他评估包括 SLE 应答指数（SRI）、发作率（使用改良 SLE 发作指数[SFI]）、泼尼松使用率和 B 细胞水平。
结果
在 268 名患者中，140 名完成了研究，128 名退出了研究。基线时红斑狼疮活动度国家评估雌激素安全版（SELENA-SLEDAI）SLE 疾病活动指数的平均±标准差评分为 7.8±3.86。SDI 评分从基线值（1.2±1.51）增加了 0.4±0.68。通过研究年 7 时，治疗相关和严重 AE 的总体发生率保持稳定或下降。在研究年 1 和研究年 7 的中点，分别有 41.9%和 75.6%的患者达到了 SRI 应答。在研究年 7 的中点，与基线相比，78.2%的患者 SELENA-SLEDAI 评分降低了≥4 分，98.4%的患者没有新的不列颠群岛狼疮评估组（BILAG）A 器官域评分，并且不超过 1 个新的 BILAG B 器官域评分，93.7%的患者疾病活动的医生整体评估没有恶化，20.6%的患者经历了≥1 次严重 SFI 发作，泼尼松剂量平均下降 31.4%，CD20+B 细胞数量中位数下降了 83.2%。
结论
这些长期暴露结果证实了贝鲁单抗在 SLE 患者中先前观察到的安全性和疗效特征。
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