#AANAM – PND Stage May Not Be Reliable Measure of Neuropathy Progression

Marisa Wexler MS avatar

by Marisa Wexler MS |

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neuropathy progression and FAP

Editor’s note: The FAP News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference.

A determined stage of polyneuropathy disability (PND) might not be a reliable indicator of neuropathy progression among people with familial amyloid polyneuropathy (FAP), an analysis of clinical trial data suggests.

Findings from this analysis were presented in the poster, “Increase in Polyneuropathy Disability Stage Does Not Predict Neuropathic Progression in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy Receiving Inotersen: Results from the NEURO-TTR Study,” at the recent American Academy of Neurology (AAN) Annual Meeting.

PND staging is a method used to broadly classify FAP patients based on their neurologic health and walking ability. There are five PND stages, ranging from stage 1 (mild sensory disturbances without walking impairments) to stage 4 (confined to a wheelchair or bedridden). Stage 3 has two levels — a and b — depending on a patient’s degree of need for walking aids.

In general, higher PND stages are associated with more severe neuropathy symptoms and a poorer quality of life. How treatment might affect these associations, however, is still unclear.

In the poster, researchers at QualityMetric, Ionis Pharmaceuticals, and the University of Pennsylvania conducted an analysis using data from the Phase 2/3 NEURO-TTR trial (NCT01737398) to better understand these associations.

NEURO-TTR evaluated the safety and efficacy of Tegsedi (inotersen), developed by Ionis, in adults with FAP. Trial results, which served as the basis for Tegsedi’s approval in the U.S., EU, and elsewhere, demonstrated the treatment was able to ease neuropathy symptoms and improve patients’ quality of life.

Researchers analyzed data from 165 patients enrolled in NEURO-TTR. Of them, 106 were given Tegsedi and 59 received a placebo in the trial.

They then divided participants into two groups — improved or no change in PND (a reduction or stabilization in PND stages) or worsening PND (an increase in PND stages) — based on whether their PND stage had worsened or not over the course of the 65-week trial.

Using statistical analyses, researchers looked for associations between treatment, worsening PND stage, neuropathy symptoms (assessed with the Neuropathy Impairment Score and related measurements), and quality of life (assessed with the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy).

Mirroring earlier results, analyses showed that treatment with Tegsedi led to improvements across neuropathy and quality-of-life outcomes.

Significant interaction effects were also seen between PND status and treatment on neuropathy symptoms. In other words, among people who experienced a worsening of PND stage, neuropathy scores also tended to worsen. However, neuropathy symptoms were much less severe for patients given Tegsedi than among those on a placebo.

A similar trend, although not statistically significant, was seen for quality of life.

In general, these findings indicate that increasing PND stage is not necessarily reflective of more severe symptoms, since two individuals with a similar increase in PND stage would be expected to have different degrees of symptom severity if one was on Tegsedi but not the other.

“This moderation effect suggests that factors other than neuropathy progression may affect PND stage, and that PND may not be a reliable indicator of neuropathy progression,” the researchers wrote.

“As such, caution should be taken when using increase in PND stage as a proxy for neuropathic progression and worsening [quality of life] in clinical and treatment decision-making,” they concluded.