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Abstract Details

Responder Analysis for the Modified Neuropathy Impairment Score + 7 and the Norfolk-Quality of Life-Diabetic Neuropathy Questionnaire in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy
General Neurology
P6 - Poster Session 6 (12:00 PM-1:00 PM)
6-008

There are no established response definitions (RDs) for mNIS+7 or Norfolk-QOL-DN in hATTR-PN, limiting assessment of whether treatments produce meaningful improvements/stabilization of neuropathic progression. RDs were estimated using multiple distribution-based approaches.

To conduct responder analyses for meaningful improvement/stabilization of neuropathic progression for the modified Neuropathy Impairment Score +7 (mNIS+7) and Norfolk-Quality of Life (QOL)-Diabetic Neuropathy (DN) questionnaire in patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN).

mNIS+7 and Norfolk-QOL-DN scores were collected at baseline and week 66 from 165 adults (inotersen: 106, placebo: 59) with hATTR-PN in the NEURO-TTR trial. RDs were estimated as half-standard deviation (SD) at baseline. Because reliability was calculable for Norfolk-QOL-DN, RDs were also estimated as standard error of measurement (SEM) and the Jacobson-Truax Reliable Change Index with 80% confidence intervals (RCI). Fisher’s exact tests compared proportions of patients showing improvement (“better”) or stabilization (“same”) between treatments.

Half-SD for mNIS+7 and Norfolk-QOL-DN total were 19.0 and 13.8, respectively. SEM and RCI for Norfolk-QOL-DN total were 6.4 and 11.5, respectively. For the mNIS+7 RD, a larger percentage of patients had better/same scores at week 66 in the inotersen arm (86%) than placebo arm (46%), p<0.001. For all Norfolk-QOL-DN total RDs, a larger percentage of patients had better/same scores at week 66 in the inotersen arm (range 67-81%) than placebo arm (35-56%), all p<0.01. For Norfolk-QOL-DN domains, a larger percentage of inotersen patients than placebo had better/same scores at week 66 for activities of daily living and large fiber/physical functioning for all RDs (all p<0.01), and for symptoms using 0.5 SD and RCI (both p<0.05).

Across multiple distribution-based RD definitions, a higher proportion of patients with hATTR-PN receiving inotersen showed meaningful improvement/stabilization in neuropathic progression at week 66 compared to placebo.  Estimation of RDs using anchor-based approaches would build on the current findings.

Authors/Disclosures
Aaron Yarlas, PhD (Ionis Pharmaceuticals)
PRESENTER
Dr. Yarlas has received personal compensation for serving as an employee of Ionis Pharmaceuticals. Dr. Yarlas has stock in Ionis Pharmaceuticals.
Andrew Lovley Andrew Lovley has received personal compensation for serving as an employee of QualityMetric.
Montserrat Vera Llonch Montserrat Vera Llonch has received personal compensation for serving as an employee of Akcea. Montserrat Vera Llonch has received stock or an ownership interest from Akcea.