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Diflunisal reduced neurological impairment in familial amyloid polyneuropathy
Patients with familial amyloid polyneuropathy who received diflunisal demonstrated reduced neurological impairment and improved quality of life compared with patients who received placebo, according to results of a randomized, double blind study.
“Our results show that diflunisal represents an alternative to liver transplantation, the current standard of care for this devastating disease,” researcher John L. Berk, MD, clinical director of the Amyloidosis Center and associate professor of medicine at Boston University School of Medicine, said in a press release. “We hope that this study prompts the identification of other widely used generic drugs for treatment of rare diseases.”
John L. Berk
Berk and colleagues evaluated data from 130 patients with familial amyloid polyneuropathy, a rare disorder caused by aggregation of variant transthyretin.
They assigned 64 patients twice-daily 250 mg diflunisal (Dolobid, Merck), an NSAID typically used in the treatment of arthritis and pain. The other 66 patients received placebo. Treatment continued for 2 years.
Difference in polyneuropathy progression between treatments was measured using the Neuropathy Impairment Score plus seven nerve tests (NIS+7). Scores ranged from 0 (no neurological deficits) to 270 (no detectable peripheral nerve function).
Researchers used the 36-Item Short-Form Health Survey to assess patient quality of life.
The NIS+7 score increased by 25 points (95% CI, 18.4-31.6) in the placebo arm compared with an increase of 8.7 points (95% CI, 3.3–14.1) in the diflunisal arm (difference, 16.3 points; 95% CI, 8.1-24.5).
At 2-year follow-up, a higher percentage of patients in the diflunisal arm (29.7% vs. 9.4%; P=.007) achieved neurological stability, defined as a less than 2-point increase in NIS+7 score.
The mean change in quality-of-life physical score was –4.9 points (95% CI, –7.6 to –2.2) in the placebo arm vs. an increase of 1.5 points (95% CI, –0.8-3.7) in the diflunisal arm (P<.001).
The quality-of-life mental score decreased by 1.1 points (95% CI, –4.3 to 2) in the placebo arm and increased by 3.7 points (95% CI, 1-6.4) in the diflunisal arm (P=.02).
“Among patients with transthyretin-type familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression in neurological impairment and preserved quality of life,” Berk and colleagues concluded. “Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for transthyretin-type familial amyloid polyneuropathy. These findings support the NIH mission of repurposing old drugs for new indications.”
Disclosure: The researchers report honoraria from, financial holdings in and other relationships with Alnylam, FoldRx Pharmaceuticals, Isis and Pfizer.