Monitoring Disease Progression and Treatment Response in hATTR Polyneuropathy

Key Takeaways:

• Because hATTR-PN is progressive and treatment is long-term, regular clinical follow-up is essential to assess disease progression and treatment response.
• No single measure is adequate. Monitoring typically combines neurologic examination, composite neuropathy scores, patient-reported outcomes, functional testing, and disease staging.
• Neurofilament light chain (NfL) is a promising biomarker of axonal injury, although its role in routine clinical practice continues to evolve.

Monitoring is an essential part of caring for patients with hATTR-PN. Regular assessments help determine whether disease-modifying therapy is slowing progression and identify patients whose neurologic function continues to decline despite treatment. Because hATTR-PN affects multiple domains, monitoring typically includes composite neuropathy scores, patient-reported outcome measures, functional assessments, disease staging, and, increasingly, biomarkers of axonal injury.

Composite neuropathy and quality-of-life measures

The modified Neuropathy Impairment Score +7 (mNIS+7) is the most widely used composite measure in clinical trials. It incorporates motor, sensory, and autonomic assessments and is useful for following disease progression over time.¹

Patient-reported outcome measures provide complementary information about symptoms and daily function that may not be fully reflected on neurologic examination. The Norfolk QOL-DN has been widely used in clinical trials alongside mNIS+7.²

Functional measures and disease staging

Functional assessments provide additional information about how neurologic impairment affects daily activities. Timed gait speed (10-meter walk test), the Rasch-built Overall Disability Scale (R-ODS), and modified body mass index can be followed over time to assess mobility, disability, and nutritional status.²

Disease-staging frameworks provide a shared vocabulary for progression. The polyneuropathy disability (PND) score and Coutinho locomotion stages grade ambulation from unimpaired walking to wheelchair dependence, and the familial amyloid polyneuropathy (FAP) system stages disease from FAP1 (sensory neuropathy, walks unaided) through FAP2 (needs walking assistance) to FAP3 (wheelchair-bound or bedridden).^3,4

Staging is more than descriptive. It drives how often a patient should be reassessed.

Neurofilament light chain as an emerging marker

Neurofilament light chain (NfL) is a promising blood biomarker of axonal injury. Plasma NfL levels are higher in patients with hATTR-PN than in healthy controls and correlate with changes in mNIS+7 over time.¹

These findings suggest NfL may be useful for monitoring disease activity and treatment response and may eventually help identify the transition from asymptomatic carrier to symptomatic disease. However, proposed diagnostic thresholds require further validation before NfL can be used routinely in clinical practice. At present, it should be considered complementary to established clinical assessments rather than a replacement for them.¹

Setting the monitoring cadence

Consensus guidance translates staging into a follow-up schedule. Patients are reassessed every 6 to 12 months, with more frequent review – approximately every 3 months – for those at later stages (2 to 3) or those not responding well to treatment.³

Stable findings across serial neurologic examinations, mNIS+7, patient-reported outcomes, ambulatory measures, and disease stage suggest that treatment is slowing disease progression. Long-term extension studies have shown that many treated patients maintain stable PND scores over several years.⁵

Progressive worsening across multiple clinical measures should prompt reassessment of disease status and the overall treatment plan. Monitoring is an important ongoing part of management rather than a one-time assessment.