Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Development of Responder Definitions for Fibromyalgia Clinical Trials.
Arnold8, Lesley M., Mease6, Philip J., Williams7, David A., Martin5, Susan A., Wang2, Fujun, Emir4, Birol, Lai3, Chinglin
Cypress Bioscience, Inc.
Eli Lilly and Company
Seattle Rheumatology Associate, Seattle, WA
Univ of MI Hlth System-Lobby M, Ann Arbor, MI
University of Cincinnati College of Medicine, Cincinnati, OH
Previous analyses of fibromyalgia (FM) clinical trial databases found patient perceptions of global improvement relied not only on improvements in pain but also on improvements in accompanying symptoms such as fatigue, sleep problems, physical functioning, and mood. These symptom and functional domains may form the components of a responder definition for FM clinical trials. The objective of this study was to develop and test responder definitions for FM clinical trials using key symptom and functional domains.
Informed by existing responder definitions for other rheumatologic disorders, 8 candidate responder definitions were developed by expert consensus. These 8 definitions were evaluated in the context of randomized placebo-controlled clinical trials of 4 medications for FM between baseline and 3 months. For each of the proposed definitions, treatment effects of the medication compared with placebo were analyzed using the Cochran-Mantel-Haenszel test. A meta-analysis of the pooled results for the 4 medications established risk ratios so as to determine the definitions that best favored medication over placebo.
Two definitions performed best in the analyses and shared common features. Both definitions included >= 30% reduction in pain and both included >= 10% improvement in physical function. They differed in that one (FM 30 short version) included >= 30% improvement in sleep or fatigue, and the other (FM 30 long version) required >= 30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was about 20% or greater for each medication and was significantly greater than placebo. The risk ratio (95% CI) in the pooled analysis of the FM 30 short version was 1.69 (1.04, 2.72), P=0.03; the risk ratio (95% CI) for the FM 30 long version was 1.60 (1.31, 1.96), P=<0.00001.
Among the 8 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for FM clinical trials that include assessments of key symptom and function domains will hopefully improve the sensitivity of clinical trials to identify meaningful improvements, leading ultimately to improved management of FM.
To cite this abstract, please use the following information:
Arnold, Lesley M., Mease, Philip J., Williams, David A., Martin, Susan A., Wang, Fujun, Emir, Birol, et al; Development of Responder Definitions for Fibromyalgia Clinical Trials. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :94