Fleischmann Roy, Furst Daniel E, Connolly-Strong Erin, Liu Jingyu, Zhu Julie, Brasington Richard
University of Texas Southwestern Medical Center, Metroplex Clinical Research Center, 8144 Walnut Hill Lane, Suite 810, Dallas, TX, 75231, USA.
Division of Rheumatology, David Geffen School of Medicine, University of California Los Angeles, Peter Morton Medical Building, 200, UCLA Medical Plaza, Suite 365-B, Los Angeles, CA, 90095, USA.
Rheumatol Ther. 2020 Jun;7(2):327-344. doi: 10.1007/s40744-020-00199-3. Epub 2020 Mar 17.
The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs).
All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports.
Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; placebo, n = 56) completed. At week 12, 163 subjects (62.9%) achieved LDA and 169 (65.3%) achieved CDAI ≤ 10 (both p < 0.0001). At week 24, 47 (61.0%) RCI-treated and 32 (42.1%) placebo-treated subjects maintained LDA (p = 0.019); 66 (85.7%) RCI-treated and 50 (65.8%) placebo-treated subjects maintained CDAI ≤ 10 (p = 0.004). No unexpected safety signals were observed.
RCI was effective and generally safe in patients with active RA despite corticosteroid/DMARD therapy. By week 12, > 60% of patients achieved LDA, which was maintained with 12 additional weeks of treatment. Most patients who achieved LDA maintained it for 3 months after RCI discontinuation.
Clinicaltrials.gov identifier NCT02919761.
本研究的目的是评估在已接受皮质类固醇和一或两种改善病情抗风湿药（DMARDs）治疗的活动性类风湿关节炎（RA）患者中，长效促肾上腺皮质激素注射液（RCI）的疗效和安全性。
所有受试者接受开放标签的RCI（80单位），每周两次，共12周（第1部分）；只有疾病活动度低[LDA；即28个关节计数的疾病活动评分和红细胞沉降率（DAS28-ESR）<3.2]的受试者在为期12周的双盲期（第2部分）被随机分配接受RCI（80单位）或安慰剂，每周两次。主要疗效终点是在第12周达到LDA的受试者比例。次要疗效终点包括在第12周至24周期间维持LDA以及在第12周和24周达到临床疾病活动指数（CDAI）≤10的受试者比例。通过不良事件报告评估安全性。
在259名入组受试者中，235名完成了第1部分；154名受试者（RCI和安慰剂各77名）进入第2部分，127名（RCI，71名；安慰剂，56名）完成。在第12周，163名受试者（62.9%）达到LDA，169名（65.3%）达到CDAI≤10（两者p<0.0001）。在第24周，47名（61.0%）接受RCI治疗和32名（42.1%）接受安慰剂治疗的受试者维持LDA（p=0.019）；66名（85.7%）接受RCI治疗和50名（65.8%）接受安慰剂治疗的受试者维持CDAI≤10（p=0.004）。未观察到意外的安全信号。
尽管接受了皮质类固醇/DMARD治疗，RCI在活动性RA患者中仍有效且总体安全。到第12周时，>60%的患者达到LDA，再治疗12周后仍维持该状态。大多数达到LDA的患者在停用RCI后3个月内维持该状态。
Clinicaltrials.gov标识符NCT02919761。
