van Vollenhoven Ronald F, Navarra Sandra V, Levy Roger A, Thomas Mathew, Heath Amy, Lustine Todd, Adamkovic Anthony, Fettiplace James, Wang Mei-Lun, Ji Beulah, Roth David
Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands.
University of Santo Tomas Hospital, Manila, Philippines.
Rheumatology (Oxford). 2020 Feb 1;59(2):281-291. doi: 10.1093/rheumatology/kez279.
This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.
In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.
A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.
Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.
ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).
这项针对III期随机、安慰剂对照的贝利尤单抗国际系统性红斑狼疮研究（BLISS）-52和BLISS-76研究的扩展研究，使非美国的系统性红斑狼疮患者能够继续接受贝利尤单抗治疗，以评估其长期安全性和耐受性，包括器官损伤累积情况。
在这项多中心长期扩展研究（葛兰素史克研究BEL112234）中，患者每4周接受一次静脉注射贝利尤单抗加标准治疗。每月评估不良事件（AE），并定期评估与安全相关的实验室参数。每48周评估一次器官损伤（SLICC/ACR损伤指数）。研究持续至贝利尤单抗上市，随后有8周的随访期。
共有738名患者进入扩展研究，735/738（99.6%）接受了一剂或多剂贝利尤单抗。不良事件（包括严重和重度不良事件）的年发生率随时间保持稳定或下降。69名（9.4%）患者发生的不良事件导致贝利尤单抗停药或退出研究。发生了11例死亡（2例在治疗后随访期间），其中1例（心源性休克）被认为可能与贝利尤单抗有关。实验室参数总体保持稳定。基线时（首次注射贝利尤单抗之前）的平均（标准差）SLICC/ACR损伤指数评分为0.6（1.02），并保持稳定。在研究的第8年，57/65（87.7%）患者的SLICC/ACR损伤指数评分与基线相比无变化，表明器官损伤累积较少。
贝利尤单抗显示出稳定的安全性，没有新的安全信号。8年期间器官损伤进展极小。
ClinicalTrials.gov，https://clinicaltrials.gov，NCT00424476（BLISS-52），NCT00410384（BLISS-76），NCT00732940（BEL112232），NCT00712933（BEL112234）。
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