Abstract | IMPORTANCE: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umeå), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012. INTERVENTION: Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years. MAIN OUTCOMES AND MEASURES: The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey [SF-36]) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data. RESULTS: By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007). CONCLUSIONS AND RELEVANCE: TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00294671.
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Authors | John L Berk, Ole B Suhr, Laura Obici, Yoshiki Sekijima, Steven R Zeldenrust, Taro Yamashita, Michael A Heneghan, Peter D Gorevic, William J Litchy, Janice F Wiesman, Erik Nordh, Manuel Corato, Alessandro Lozza, Andrea Cortese, Jessica Robinson-Papp, Theodore Colton, Denis V Rybin, Alice B Bisbee, Yukio Ando, Shu-ichi Ikeda, David C Seldin, Giampaolo Merlini, Martha Skinner, Jeffery W Kelly, Peter J Dyck, Diflunisal Trial Consortium |
Journal | JAMA
(JAMA)
Vol. 310
Issue 24
Pg. 2658-67
(Dec 25 2013)
ISSN: 1538-3598 [Electronic] United States |
PMID | 24368466
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Diflunisal
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Topics |
- Aged
- Amyloid Neuropathies, Familial
(drug therapy, physiopathology)
- Anti-Inflammatory Agents, Non-Steroidal
(therapeutic use)
- Body Mass Index
- Diflunisal
(therapeutic use)
- Disease Progression
- Double-Blind Method
- Female
- Humans
- Male
- Middle Aged
- Quality of Life
- Survival Analysis
- Treatment Outcome
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