Wallace D J, Hobbs K, Clowse M E B, Petri M, Strand V, Pike M, Merrill J T, Leszczyński P, Neuwelt C M, Jeka S, Houssiau F, Keiserman M, Ordi-Ros J, Bongardt S, Kilgallen B, Galateanu C, Kalunian K, Furie R, Gordon C
Cedars-Sinai Medical Center, Los Angeles, California.
Denver Arthritis Clinic, Denver, Colorado.
Arthritis Care Res (Hoboken). 2016 Apr;68(4):534-43. doi: 10.1002/acr.22694.
The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL).
Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed.
A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab.
Open-label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.
主要目的是评估中重度系统性红斑狼疮患者重复使用依帕珠单抗治疗的长期安全性。次要目的是评估长期疗效和健康相关生活质量（HRQOL）。
来自12周IIb期随机安慰剂对照EMBLEM研究的符合条件的患者入选开放标签扩展（OLE）研究SL0008。在SL0008研究中，患者在重复12周周期的第0周和第2周接受1200mg依帕珠单抗输注，加标准治疗。安全措施包括治疗中出现的不良事件（TEAE）和严重TEAE。疗效指标包括联合治疗反应、不列颠群岛狼疮评估组评分、系统性红斑狼疮疾病活动指数评分以及医生和患者对疾病活动的整体评估。还评估了每日皮质类固醇总剂量和HRQOL（通过简短36健康调查）。
进入SL0008研究的203例患者中，共有113例（55.7%）继续接受依帕珠单抗治疗直至研究结束（总累积暴露：381.3患者年，中位暴露：845天，最大暴露：1185天/约3.2年）。192例患者（94.6%）报告了TEAE；最常见的是感染和寄生虫感染（68.0%，138例患者）。51例患者（25.1%）报告了严重TEAE，14例患者（6.9%）发生了严重感染。在接受治疗108周的患者（n = 116）中，皮质类固醇中位剂量从OLE筛查时的10.0mg/天降至第108周时的5.0mg/天。EMBLEM中疗效和HRQOL指标的改善在OLE中得以维持，而安慰剂组患者在改用依帕珠单抗后疾病活动度也有类似改善。
开放标签的依帕珠单抗治疗在长达3.2年的时间里耐受性良好，与疾病活动度和HRQOL的持续改善相关，同时类固醇用量减少。
