Abstract Details

Title Safety and Efficacy of Long-Term Diflunisal Administration in Familial Amyloid Polyneuropathy

Topic Peripheral Nerve

Presentation(s) (-)

Poster/Presentation
Number 009

Objective

Background While the current standard form of care for FAP patients is liver transplantation, it has a number of limitations. Furthermore, many FAP patients are not good transplant candidates because of their age and/or advanced disease status. Therefore, it is desirable to develop a general, convenient, and non-invasive alternative therapeutic strategy to ameliorate FAP.

Design/Methods In this open-label historical control study, diflunisal was administered orally at 500 mg/day to 18 late-onset ATTR Val30Met FAP patients. The observation period ranged from 2 to 84months (mean 35.0 ± 24.0 months). Treatment effect was assessed by serial measurements of ulnar and tibial nerve compound muscle action potential (CMAP) amplitudes, clinical FAP score, cardiac function tests, and serum TTR concentration and stability. The historical control group consisted of 27 late-onset ATTR Val30Met FAP patients.

Results Diflunisal-related adverse events included deterioration of renal function and thrombocytopenia resulted in discontinuation of the study drug in two patients. Five patients dropped out due to reasons unrelated to diflunisal. Orally administered diflunisal significantly increased serum TTR concentration (p=0.001) and stabilized TTR tetramer structure in each patient. The %decreases of ulnar nerve CMAP amplitude in the diflunisal treatment group and the control group were 6.6% ± 14.7%/year and 30.5% ± 15.2%/year, respectively (p=0.0003). The ratios of patients in whom tibial nerve CMAP became undetectable during the follow-up period were 33.3% (4/12) in the diflunisal treatment group and 100% (10/10) in controls (p=0.002).

Conclusions Diflunisal was well-tolerated by most FAP patients and increased serum TTR concentration and stability. This study provides Class III evidence that diflunisal significantly slows the deterioration rates of ulnar and tibial nerve CMAP compared to the controls.

Authors/Disclosures
Yoshiki Sekijima, MD, PhD PRESENTER	Yoshiki Sekijima, "MD, PhD" has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam. Yoshiki Sekijima, "MD, PhD" has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Pfizer.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gen Sobue, MD (Nagoya University School Of Medicine/Dept. of Neurology)	Dr. Sobue has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mistubishi Tanabe Pharma Corporation. Dr. Sobue has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Nippon Chemiphar Co., Ltd.. Dr. Sobue has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Mistubishi Tanabe Pharma Corporation. Dr. Sobue has received personal compensation in the range of $0-$499 for serving as an Expert Witness for Takeda Pharmaceutical Company Limited..
	No disclosure on file
Kathie M. Bishop, PhD	Dr. Bishop has received personal compensation for serving as an employee of Acadia Pharmaceuticals, Inc. . Dr. Bishop has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for DTx Pharma. Dr. Bishop has stock in Acadia Pharmaceuticals, Inc..

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