阿达木单抗剂量滴定治疗长期临床缓解的类风湿关节炎患者：IV 期 PREDICTRA 研究结果。
Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study.
机构信息
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
NIHR Leeds Biomedical Research Centre, Leeds, UK.
出版信息
Ann Rheum Dis. 2020 Aug;79(8):1023-1030. doi: 10.1136/annrheumdis-2020-217246. Epub 2020 May 13.
OBJECTIVE
To investigate the association between baseline disease activity and the occurrence of flares after adalimumab tapering or withdrawal in patients with rheumatoid arthritis (RA) in sustained remission.
METHODS
The PREDICTRA phase IV, randomised, double-blind (DB) study (Imact of esidual Inflammation Detected via Imaging Tchniques, rug Levels, and Patient Characteristics on the Outcome of Dose Taperng of Adalimumab in linical Remission Rheumatoid Arhritis () Patients) enrolled patients with RA receiving adalimumab 40 mg every other week who were in sustained remission ≥6 months. After a 4-week, open-label lead-in (OL-LI) period, patients were randomised 5:1 to DB adalimumab taper (every 3 weeks) or withdrawal (placebo) for 36 weeks. The primary endpoint was the association between DB baseline hand and wrist MRI-detected inflammation with flare occurrence.
RESULTS
Of 146 patients treated during the OL-LI period, 122 were randomised to taper (n=102) or withdrawal (n=20) arms. Patients had a mean 12.9 years of active disease and had received adalimumab for a mean of 5.4 years (mean 2.2 years in sustained remission). Overall, 37 (36%) and 9 (45%) patients experienced a flare in the taper and withdrawal arms, respectively (time to flare, 18.0 and 13.3 weeks). None of the DB baseline disease characteristics or adalimumab concentration was associated with flare occurrence after adalimumab tapering. Approximately half of the patients who flared regained clinical remission after 16 weeks of open-label rescue adalimumab. The safety profile was consistent with previous studies.
CONCLUSIONS
Approximately one-third of patients who tapered adalimumab versus half who withdrew adalimumab experienced a flare within 36 weeks. Time to flare was numerically longer in the taper versus withdrawal arm. Baseline MRI inflammation was not associated with flare occurrence.
TRIAL REGISTRATION NUMBER
NCT02198651, EudraCT 2014-001114-26.
目的
研究类风湿关节炎（RA）持续缓解患者阿达木单抗逐渐减量或停药后，基线疾病活动度与病情复发的相关性。
方法
PREDICTRA 是一项 IV 期、随机、双盲（DB）研究（残留炎症通过影像学技术、药物水平和患者特征对阿达木单抗剂量减少的临床缓解 RA 患者结局的影响研究），纳入了接受阿达木单抗 40mg 每两周一次治疗且持续缓解≥6 个月的 RA 患者。在为期 4 周的开放标签导入期（OL-LI）后，患者按 5：1 随机分为 DB 阿达木单抗逐渐减量（每 3 周一次）或停药（安慰剂）组，共 36 周。主要终点是 DB 基线手部和腕部 MRI 检测到的炎症与复发的相关性。
结果
在 OL-LI 期间接受治疗的 146 例患者中，122 例被随机分为逐渐减量（n=102）或停药（n=20）组。患者的平均患病时间为 12.9 年，阿达木单抗治疗的平均时间为 5.4 年（持续缓解期的平均时间为 2.2 年）。总体而言，逐渐减量组和停药组分别有 37（36%）和 9（45%）例患者出现病情复发（复发时间分别为 18.0 周和 13.3 周）。阿达木单抗逐渐减量后，DB 基线疾病特征或阿达木单抗浓度均与病情复发无关。约一半复发的患者在接受 16 周的开放标签阿达木单抗补救治疗后恢复临床缓解。安全性特征与既往研究一致。
结论
阿达木单抗逐渐减量组约有三分之一的患者和停药组一半的患者在 36 周内出现病情复发。与停药组相比，逐渐减量组的复发时间更长。基线 MRI 炎症与病情复发无关。
临床试验注册号
NCT02198651，EudraCT 2014-001114-26。
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