Abstract Details

Title 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

Topic General Neurology

Presentation(s) General Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 094

Objective To examine whether increased polyneuropathy disability (PND) stage corresponds with worsening in clinician- and patient-reported neuropathic measures (the modified Neuropathy Impairment Score +7 [mNIS+7] and Norfolk-Quality of Life-Diabetic Neuropathy [Norfolk-QOL-DN], respectively) in patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) receiving inotersen.

Background PND staging broadly classifies neurologic health and ambulation for patients with hATTR-PN. PND ranges from stage 0 (no neurological/ambulatory impairment) to 4 (confined to wheelchair/bedridden). Patients in later PND stages exhibit worse neuropathy and QOL than patients in earlier stages.

Design/Methods mNIS+7 and Norfolk-QOL-DN were administered at baseline and following 65 weeks of treatment to adult patients with hATTR-PN randomized to receive inotersen or placebo in the NEURO-TTR trial (ClinicalTrials.gov ID: NCT01737398). Patients were classified into two subgroups: “PND worse” (PND stage increased from baseline to week 65) or “PND same/better” (PND stage unchanged/decreased). Analysis of variance tested main effects and the interaction of treatment and PND subgroup on mean changes in mNIS+7 and Norfolk-QOL-DN.

Results Twenty of 84 patients receiving inotersen, and 13/52 patients receiving placebo, were classified as “PND worse.” For mNIS+7, main and interaction effects were statistically significant (ps<0.001), reflecting substantially larger differences in mean change between “PND worse” and “PND same/better” for placebo (46.7 vs. 16.3) than for inotersen (6.3 vs. 3.6). For Norfolk-QOL-DN, main effects were statistically significant (ps<0.05) although not the interaction effect (p=0.19). Larger differences in Norfolk-QOL-DN mean change were observed between “PND worse” and “PND same/better” for placebo (21.6 vs. 7.2) than for inotersen (2.7 vs. -1.2).

Conclusions Preliminary results suggest that increasing PND stage was not associated with worsening on granular measures of neuropathy for patients with hATTR-PN receiving inotersen. This dissociation suggests that factors other than neuropathy progression may affect PND stage and that PND may not be a reliable outcome for neuropathy progression in patients with systemic disorders.

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.
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.
Duncan Brown (Akcea Therapeutics, Inc)	Duncan Brown has received personal compensation for serving as an employee of Akcea Therapeutics, Inc. Duncan Brown has received stock or an ownership interest from Akcea Therapeutics, Inc.
	No disclosure on file
Sami L. Khella, MD, FAAN (Presbyterian Med Ctr/Dept of Neuro)	Dr. Khella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eidos.
Chafic Y. Karam, MD (University of Pennsylvania)	Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alnylam. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexon. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvig. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Applied therapeutics. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Intellia. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Takeda. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Vertex.

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