An evaluation of colchicine as an alternative to inhaled corticosteroids in moderate asthma

被引:28
作者
Fish, JE
Peters, SP
Chambers, CV
McGeady, SJ
Epstein, KR
Boushey, HA
Cherniack, RM
Chinchilli, VM
Drazen, JM
Fahy, JV
Hurd, SS
Israel, E
Lazarus, SC
Lemanske, RF
Martin, RJ
Mauger, EA
Sorkness, C
Szefler, SJ
机构
[1] BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, BOSTON, MA USA
[3] UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA
[4] MILTON S HERSHEY MED CTR, HERSHEY, PA USA
[5] UNIV WISCONSIN, MADISON, WI 53706 USA
[6] NATL JEWISH MED & RES CTR, DENVER, CO USA
[7] NHLBI, BETHESDA, MD 20892 USA
关键词
D O I
10.1164/ajrccm.156.4.9703012
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 mu g daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomised to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81 +/- 1.38 versus 2.11 +/- 2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.
引用
收藏
页码:1165 / 1171
页数:7
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