Medications improve FAP survival regardless of patients’ age at onset

Study finds liver transplant only improves survival in early onset of disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Disease-modifying medications can significantly improve survival outcomes among people with familial amyloid polyneuropathy (FAP) no matter what age the disease begins, whereas a liver transplant only improves survival in early-onset FAP.

That’s according to “Disease-Modifying Drugs Extend Survival in Hereditary Transthyretin Amyloid Polyneuropathy,” which was published in the Annals of Neurology.

FAP, or hereditary transthyretin amyloidosis with polyneuropathy, is caused by mutations in the gene that provides instructions to make the transthyretin protein.

As a result of these mutations, transthyretin forms toxic clumps in tissues, mainly those in the nerves outside the brain and spinal cord, causing damage that leads to disease symptoms.

There is no cure for FAP, but treatment can slow its course. These include a liver transplant, along with several disease-modifying drugs (DMDs) that can reduce toxic transthyretin levels.

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Survival with DMDs, liver transplant

Scientists in Japan reviewed outcomes from 201 FAP patients (113 men, 88 women) treated over three decades at their center. Most (66.2%) carried Val30Met, the most common FAP-causing mutation. Among them, 53 didn’t receive any treatment, 94 were treated with DMDs only, and 54 underwent a liver transplant with DMDs (24) or without DMDs (30).

DMDs included Onpattro (patisiran), tafamidis — sold as Vyndaqel/Vyndamax and approved for treating adults with FAP in Japan, but not the U.S. — and/or diflunisal,  an anti-inflammatory medication sold as Dolobid that’s shown beneficial effects in FAP.

Nearly all the patients given treatment (93.3%) were estimated to be alive 10 years after the initial onset of their disease. Among those who received no treatment, less than half (42%) were estimated to be alive a decade after their disease onset.

“According to our real-world data from a single referral center, we found positive effects of disease-modifying therapies on long-term survival,” the researchers wrote.

Using DMDs was associated with statistically significant improvements in survival both for those with early-onset FAP, where symptoms develop before age 50, and for late-onset FAP, where symptoms don’t appear until later in life. DMDs even led to significantly better survival for those who had disease onset at age 60 or later.

Liver transplant led to prolonged survival in early-onset FAP, but the effect of liver transplant in late-onset disease wasn’t statistically significant.

“Our … data suggest that DMDs improved survival not only in patients with early-onset disease but also in patients with late-onset disease, in whom [liver transplant] previously had little effect on survival,” the scientists wrote.

DMDs also significantly improved survival of patients who initially developed either nerve damage (neuropathy) or other symptoms. A liver transplant didn’t significantly improve survival in those who first developed symptoms other than neuropathy.

The findings suggest both DMDs and a liver transplant “may significantly improve long-term survival in patients with [FAP],” the researchers wrote, with the benefits of DMDs being for both early and late-onset disease.

The analysis is limited by its use of data from just one center, the researchers said. “How generally our findings apply to other countries or regions with different medical situations remains to be determined,” they wrote noting to compare “effects on survival of patients between DMDs, further prospective, long-term, and multicenter studies of well-characterized [FAP patients groups] should be needed.”