Division of Rheumatology, Cedars-Sinai Medical Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Centre for Rheumatology/Division of Medicine, University College London, London, UK.
Rheumatology (Oxford). 2021 Nov 3;60(11):5379-5389. doi: 10.1093/rheumatology/keab115.
Atacicept reduced SLE disease activity in the phase 2b ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II.
In the 24-week, randomized, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary endpoint. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares.
In total, 253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4-93.2%), and 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo.
Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy.
ClinicalTrials.gov, http://clinicaltrials.gov, NCT02070978.
Atacicept 在 2b 期 ADDRESS II 研究中降低了 SLE 疾病活动度，特别是在筛选时处于高疾病活动度（HDA；SLEDAI-2K≥10）的患者中。我们评估了 ADDRESS II 的长期扩展（LTE）中 atacicept 的长期安全性和疗效。
在 24 周、随机、双盲、安慰剂对照的 ADDRESS II 研究中，患者每周接受 atacicept（75 或 150mg）或安慰剂治疗。在 LTE 中，接受 atacicept 治疗的患者继续以相同剂量接受 atacicept 治疗；接受安慰剂治疗的患者转换为 atacicept 150mg。长期安全性是主要终点。次要终点包括 SLE 应答指数（SRI）-4 和 SRI-6 应答率和发作。
共有 253 名患者进入 ADDRESS II LTE；88 名患者接受 atacicept 150mg，82 名患者接受 atacicept 75mg，83 名患者接受安慰剂/atacicept 150mg。LTE 中的中位治疗持续时间为 83.8 周。各组治疗期间出现的不良事件（TEAE）发生率相似（90.4-93.2%），在 atacicept 150mg、atacicept 75mg 和安慰剂/atacicept 150mg 组中，分别有 12.5%、14.6%和 21.7%的患者报告了严重的 TEAEs。因 TEAEs 而停药的患者比例分别为 5.7%、4.9%和 10.8%。在改良意向治疗人群和 HDA 人群中，继续使用 atacicept 治疗维持了 SRI-4 和 SRI-6 应答率，与最初接受安慰剂的患者相比，持续使用 150mg atacicept 的患者首次严重发作的风险降低，且首次严重发作的时间延长。
在 SLE 患者中，长期使用 atacicept 150mg 治疗具有可接受的安全性，且疗效持久。
ClinicalTrials.gov，http://clinicaltrials.gov，NCT02070978。
