Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Leeds NIHR Biomedical Research Centre, Leeds, UK.
University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
Arthritis Res Ther. 2023 Apr 22;25(1):67. doi: 10.1186/s13075-023-03038-2.
AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy.
During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP]) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24).
Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate.
A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued.
NCT02504268 (ClinicalTrials.gov), registered July 21, 2015.
AVERT-2（一项 IIIb 期、两阶段研究）评估了 abatacept + 甲氨蝶呤与甲氨蝶呤单药治疗在甲氨蝶呤初治、抗瓜氨酸化蛋白抗体阳性、早期（≤6 个月）、活动性 RA 患者中的疗效。本亚分析旨在探讨在第 24 周达到简化疾病活动指数（SDAI）缓解主要终点的个别患者是否能够持续缓解 1 年，然后在治疗改变后维持缓解。
在 56 周的诱导期（IP）期间，患者被随机分配接受每周一次皮下 abatacept 125mg+甲氨蝶呤或 abatacept 安慰剂+甲氨蝶呤。在第 40 周和第 52 周达到 SDAI 缓解（≤3.3）的完成 IP 的患者进入为期 48 周的降级（DE）期。接受 abatacept+甲氨蝶呤治疗的患者被重新随机分配继续每周接受 abatacept+甲氨蝶呤治疗，或降级后停用 abatacept（24 周后），或接受 abatacept 单药治疗。评估持续达到 SDAI 和布尔缓解以及使用 C 反应蛋白（DAS28[CRP]）的 28 个关节疾病活动评分（DAS28[CRP]）<2.6 的患者比例。对于在第 24/40/52 周达到早期持续 SDAI 缓解的患者，评估疾病活动类别之间和个体轨迹之间的流动；还评估了较晚缓解的患者（第 40/52 周但不是第 24 周）的流动。
在接受 abatacept+甲氨蝶呤治疗的患者中（n/N=451/752），在 IP 第 24 周，22%的患者达到 SDAI 缓解，17%的患者达到布尔缓解，42%的患者达到 DAS28（CRP）<2.6；其中，分别有 56%、58%和 74%的患者在整个 IP 第 40/52 周持续缓解。在 IP 第 24/40/52 周持续缓解的患者中，82%（14/17）接受每周 abatacept+甲氨蝶呤治疗、81%（13/16）接受 abatacept 单药治疗、63%（12/19）降级/停用 abatacept、65%（11/17）接受 abatacept 安慰剂+甲氨蝶呤的患者在 DE 期结束时达到 SDAI 缓解；除 abatacept 安慰剂+甲氨蝶呤组外，所有组的缓解率均高于较晚缓解的患者。
在接受 abatacept+甲氨蝶呤治疗的患者中，相当一部分患者在 IP 第 24 周达到临床终点后，持续缓解至第 52 周。在第 52 周达到早期和持续 SDAI 缓解的患者中，如果继续每周接受 abatacept 治疗，则在 DE 期间维持缓解的患者比例更高。
NCT02504268（ClinicalTrials.gov），2015 年 7 月 21 日注册。
