Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis
Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis
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DOI：
10.1002/art.1780390704
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发表时间：
1996-07-01
影响因子：
--
通讯作者：
Yocum, D
中科院分区：
文献类型：
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作者：
Campion, GV;Lebsack, ME;Yocum, D
Objective.初步评价重组人白细胞介素-1受体拮抗剂（rHuIL-1 Ra）不同剂量水平和给药频率治疗类风湿关节炎（RA）患者的安全性和有效性。方法。175例活动性RA患者参加了通过皮下注射施用rHuIL-1 Ra的随机、双盲试验。试验中有9个治疗组。在最初的3周治疗阶段，患者用20、70或200 mg rHuIL-1 Ra治疗，每周给药一次、3次或7次，随后是4周的维持阶段，在此期间，所有患者每周接受一次治疗阶段剂量。为了保持研究的盲性，患者在不施用rHuIL-1 Ra的日子每天接受rHuIL-1 Ra或安慰剂的注射。重组HuIL-1 Ra耐受良好。最常见的不良事件是注射部位反应，有62%的患者报告，导致8例患者（5%）提前退出研究。5例患者（3%）发生了与剂量或给药频率无关的严重不良反应。由于缺乏安慰剂组和多个小治疗组，无法做出关于疗效的明确声明。然而，在3周治疗期结束时，通过肿胀关节数量、研究者和患者对疾病活动度、疼痛评分和C反应蛋白水平的评估，每日给药似乎比每周给药更有效。这些初步数据表明，rHuIL-1 Ra可以通过皮下注射安全地施用给RA患者。给药频率在确定临床应答方面似乎很重要，每日给药可提供最大获益。一项安慰剂对照试验正在进行中，以进一步评估rHuIL-1 Ra在RA患者中的临床有用性并更好地定义rHuIL-1 Ra的适当剂量。
Objective. To preliminarily evaluate the safety and efficacy of different dose levels and dosing frequencies of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in the treatment of patients with rheumatoid arthritis (RA).Methods. One hundred seventy-five patients with active RA were enrolled in a randomized, double-blind trial of rHuIL-1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3-week treatment phase, patients were treated with 20, 70, or 200 mg rHuIL-1Ra, administered either once, 3 times, or 7 times per week followed by a 4-week maintenance phase, during which all patients received the treatment-phase dose once per week. To maintain the blindness of the study, patients received daily injections of either rHuIL-1Ra or placebo on the days rHuIL-1Ra was not administered.Results. Recombinant HuIL-1Ra was well tolerated. The most frequent adverse event was injection-site reactions, which were reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adverse reactions unrelated to dose or dosing frequency. Due to the lack of a placebo arm and to the multiple small treatment groups, a definitive statement regarding efficacy could not be made. However, by the end of the 3-week treatment phase, daily dosing appeared more effective than weekly dosing when assessed by the number of swollen joints, the investigator and patient assessments of disease activity, pain score, and C-reactive protein levels.Conclusion. These preliminary data suggest that rHuIL-1Ra may be safely administered by subcutaneous injection to RA patients. The frequency of dosing appears to be important in determining clinical response, with daily administration providing the most benefit. A placebo-controlled trial is in progress to further assess the clinical usefulness and to better define appropriate doses of rHuIL-1Ra in patients with RA.