Treated FAP patients generally stable; some still get worse: Study
Data from 35 patients analyzed to learn about routine clinical care outcomes
People with familial amyloid polyneuropathy (FAP) who were given disease-modifying treatments in routine clinical care show relatively stable disease over time, but a substantial proportion still showed signs of disease progression throughout follow-up, a real-world study in France shows.
“In routine care, the overall population of patients remains stable,” the researchers wrote. “However, there is significant [variability] in response to treatment, hence the crucial importance of rigorous … monitoring.”
The study, “Real-life experience with disease-modifying drugs in hereditary transthyretin amyloid polyneuropathy: A clinical and electrophysiological appraisal,” was published in the European Journal of Neurology.
In FAP, also called hereditary transthyretin amyloid polyneuropathy (ATTRv-PN), an abnormal version of the transthyretin protein is produced that clumps up and damages tissues and especially affects the peripheral nerves, which reside outside the brain and spinal cord. Some patients can also have heart problems.
There is no cure, but a number of disease-modifying treatments have become available in recent years that have substantially improved outcomes with the rare progressive disease. Long-term follow-up studies to track outcomes for patients outside clinical trials remain in short supply, however.
FAP clinical outcomes in clinical care
Here, researchers in France retrospectively analyzed data from 35 FAP patients (26 men, nine women) seen at a single center between 2014 and 2023 to learn more about clinical outcomes for FAP patients in routine clinical care. The patients had a median age of 58 and about a third (34.3%) were of Portuguese origin, Portugal being one of the countries where FAP is more common.
FAP treatments included transthyretin stabilizers, gene silencers, a combination of both, and liver transplant. Transthyretin stabilizers include tafamidis meglumine, which is approved as Vyndaqel for early-stage FAP in the European Union, but not the U.S. Gene silencers include Amvuttra (vutrisiran), Tegsedi (inotersen), and Onpattro (patisiran).
Clinical disease progression was evaluated at annual visits using the Neuropathy Impairment Scale (NIS), the most commonly used clinical assessment of FAP progression, and other measures of disease severity. Data from electrophysiological studies assessed the electrical activity and health of peripheral nerves, and biomarkers of heart damage were used to assess heart health.
Patients were followed for a median of three years and up to four years, during which they “tended to be clinically and electrophysiologically stable,” the researchers wrote.
The median NIS score increased — reflecting worsening neuropathy — by 10 points in the first year of follow-up and by 4.25 points per year over the next three years. That’s a slower disease progression than the estimated 14.3-point annual NIS score worsening that would be expected in untreated FAP patients, the researchers said.
On average, other clinical scores related to disease progression also remained generally stable throughout follow-up, as did electrophysiological assessments and heart damage biomarkers.
Differences in individual responses
Still, responses at the individual level varied, with around 40% of patients showing signs of disease worsening over follow-up, depending on the measure being used. For example, 45% of patients exhibited worsened NIS scores, defined as at least a 2-point increase, as of the last follow-up.
Clinical worsening occurred most often early on, which the scientists believe is related to the time it takes for therapies to start working.
“This study shows an overall stability of our [patient group], regardless of the treatments used,” the researchers wrote, adding the findings “demonstrate the overall efficacy of ATTRv-PN treatments in routine care.”
The fact that some patients still showed disease progression, “highlights the need for regular clinical and electrophysiological assessment to improve the treatment strategy,” wrote the scientists, who noted that several factors, including genetics, coexisting health issues, disease stage, and the specific treatment that’s first used, could help explain why some patients still deteriorate.
Most patients used Vyndaqel at the start of the study because that was the only available treatment in France, but others have since become available. There haven’t been studies to directly compare different treatments in clinical practice.
“Further research is needed to better understand the mechanisms and effects of different therapies on disease progression,” wrote the researchers, who also used the data to identify which clinical or electrophysiological measures were most sensitive for detecting patients’ disease progression.
They found that the clinical scale best able to detect changes in disease severity was the overall neuropathy limitations scale (ONLS). While electrophysiological measures were good monitoring tools, they “were no more sensitive than the clinical scores,” the researchers wrote, noting the “results must be confirmed in a larger [group] of patients.”
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