Quality of life assessment in amyloid transthyretin (ATTR) amyloidosis

Abstract

Background: Amyloid transthyretin (ATTR) amyloidosis is caused by the systemic deposition of transthyretin molecules, either normal (wild-type ATTR, ATTRwt) or mutated (variant ATTR, ATTRv). ATTR amyloidosis is a disease with a severe impact on patients' quality of life (QoL). Nonetheless, limited attention has been paid to QoL so far, and no specific tools for QoL assessment in ATTR amyloidosis currently exist. QoL can be evaluated through patient-reported outcome measures (PROMs), which are completed by patients, or through scales, which are compiled by clinicians. The scales investigate QoL either directly or indirectly, i.e., by assessing the degree of functional impairment and limitations imposed by the disease.

Design: Search for the measures of QoL evaluated in phase 2 and phase 3 clinical trials on ATTR amyloidosis.

Results: Clinical trials on ATTR amyloidosis have used measures of general health status, such as the Short Form 36 Health Survey (SF-36), or tools developed in other disease settings such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or adaptations of other scales such as the modified Neuropathy Impairment Score +7 (mNIS+7).

Conclusions: Scales or PROMs for ATTR amyloidosis would be useful to better characterize newly diagnosed patients and to assess disease progression and response to treatment. The ongoing ITALY (Impact of Transthyretin Amyloidosis on Life qualitY) study aims to develop and validate 2 PROMs encompassing the whole phenotypic spectrum of ATTRwt and ATTRv amyloidosis, that might be helpful for patient management and may serve as surrogate endpoints for clinical trials.

Keywords: ATTR amyloidosis; PROMs; quality of life; scales; transthyretin.

FIGURE 1

New patient‐reported outcome measures (PROMs) to capture the clinical complexity of variant and wild‐type amyloid transthyretin amyloidosis (ATTRv/ATTRwt). See text for details. Scales and PROMs are reported in italic and in bold, respectively. 6MWT, 6‐min walking test; 10MWT, 10‐metre walking test; COMPASS‐31, COMPosite Autonomic Symptom Scale 31; EQ5D‐3L, Euro QoL 5‐Dimensions 3‐Levels; FAP‐RODS, Familial Amyloid Polyneuropathy specific Rasch‐built Overall Disability Scale; HADS, Hospital Anxiety and Depression Scale; KCCQ, Kansas City Cardiomyopathy Questionnaire; KNS, Kumamoto Neurologic Scale; mNIS+7, modified Neuropathy Impairment Score +7; Norfolk QoL‐DN, Norfolk Quality of Life‐Diabetic Neuropathy questionnaire; NYHA, New York Heart Association; PND, Polyneuropathy Disability Score; SF‐36, Short Form 36 Health Survey; WPAI‐SH, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem