Khoury Samia J, Healy Brian C, Kivisäkk Pia, Viglietta Vissia, Egorova Svetlana, Guttmann Charles R G, Wedgwood Josiah F, Hafler David A, Weiner Howard L, Buckle Guy, Cook Sandra, Reddy Susheel
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Arch Neurol. 2010 Sep;67(9):1055-61. doi: 10.1001/archneurol.2010.222.
Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a β2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy.
To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment.
Single-center double-masked clinical trial.
Academic research. Patients Subjects with relapsing-remitting multiple sclerosis.
In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point. The classification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol.
Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P = .005) and 12-month (P = .04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P = .03). Immunologically, IL-13 and interferon-γ production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P < .05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment.
Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis.
clinicaltrials.gov Identifier: NCT00039988.
白细胞介素12（IL-12）是一种促进1型辅助性T细胞生成的细胞因子，在多发性硬化症中水平升高。硫酸沙丁胺醇是一种β2肾上腺素能激动剂，可降低IL-12表达，因此我们测试了沙丁胺醇作为醋酸格拉替雷治疗附加疗法的效果。
研究沙丁胺醇治疗作为附加疗法对开始接受醋酸格拉替雷治疗的患者的临床和免疫效果。
单中心双盲临床试验。
学术研究机构。患者为复发缓解型多发性硬化症患者。
在这项单中心双盲临床试验中，复发缓解型多发性硬化症患者被随机分为两组，一组接受皮下注射醋酸格拉替雷（20毫克）加每日口服一剂安慰剂，持续2年；另一组接受皮下注射醋酸格拉替雷（20毫克）加每日口服一剂沙丁胺醇，持续2年。主要临床疗效指标是2年时多发性硬化功能综合评分的变化，主要免疫终点是每个研究时间点IL-13和干扰素γ表达的变化。由于这是第一项探讨醋酸格拉替雷加沙丁胺醇疗效的II类临床试验，该试验每个问题的证据分类级别均为C级。
44名受试者被随机分配接受醋酸格拉替雷加沙丁胺醇或醋酸格拉替雷加安慰剂治疗，39名受试者参与分析。在醋酸格拉替雷加沙丁胺醇组，6个月（P = 0.005）和12个月（P = 0.04）时多发性硬化功能综合评分有所改善，但24个月时未改善。醋酸格拉替雷加沙丁胺醇组首次复发时间也出现延迟（P = 0.03）。在免疫学方面，两个治疗组中IL-13和干扰素γ的产生均减少，在12个月时观察到对IL-13产生的治疗效果（P < 0.05）。不良事件一般较轻，只有3例中度或重度事件被认为与治疗有关。
醋酸格拉替雷加沙丁胺醇治疗耐受性良好，可改善多发性硬化症患者的临床结局。
clinicaltrials.gov标识符：NCT00039988。
