Rate of neuropathic progression in hereditary transthyretin amyloidosis with polyneuropathy and other peripheral neuropathies: a systematic review and meta-analysis

Abstract

Background: We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT).

Methods: Literature searches identified studies reporting neuropathic progression, measured by Neuropathy Impairment Score (NIS) or NIS-Lower Limbs (NIS-LL). Our study also included unpublished data from a clinical registry of patients who were diagnosed with different peripheral neuropathies and seen at the Oregon Health & Science University (OHSU) during 2016-2020. Meta-analysis and meta-regression models examined and compared annual progression rates, calculated from extracted data, between studies of ATTRv-PN and other peripheral neuropathies.

Results: Data were synthesized from 15 studies in which NIS and/or NIS-LL total scores were assessed at least twice, with ≥12 weeks between assessments, among untreated patients with ATTRv-PN or other peripheral neuropathies. Meta-analysis models yielded that the annual progression rate in NIS total scores was significantly different from zero for studies in ATTRv-PN and CMT (11.77 and 1.41; both P < 0.001), but not DPN (- 1.96; P = 0.147). Meta-regression models showed significantly faster annual progression in studies in ATTRv-PN, which statistically exceeded that in other peripheral neuropathies by 12.45 points/year for NIS, and 6.96 for NIS-LL (both P < 0.001).

Conclusions: Peripheral nervous function deteriorates more rapidly in patients with ATTRv-PN than for other peripheral neuropathies. These findings may improve understanding of the natural history of neuropathy in ATTRv-PN, facilitate early diagnosis, and guide the development of assessment tools and therapies specifically targeting neuropathic progression in this debilitating disease.

Keywords: Hereditary transthyretin amyloidosis with polyneuropathy; Meta-analysis; Neuropathic progression; Neuropathy impairment score; Peripheral neuropathy.

Fig. 1

PRISMA Flowchart of Study Section. Abbreviations: ATTRv-PN, hereditary transthyretin amyloidosis with polyneuropathy; NIS, Neuropathy Impairment Score; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Fig. 2

Risk of Bias Assessment for RCTs Included in Data Synthesis: Summary for Items of Bias Within and Across Studies. a. Risk of bias for all RCTs included in the meta-analysis presented for individual trials (represented by author name and year) as low, high, or unclear risk of bias in each attribute assessed; b. risk of bias for all RCTs included in the meta-analysis presented as the percentages of trials with low, high, or unclear risk of bias for each attribute assessed. Abbreviations: RCT, randomized-controlled trial

Fig. 3

Weighted Mean Annual Rate of Change in NIS Total Score in Studies of Patients with CMT, DPN, and ATTRv-PN. Pooled effect estimates were calculated based on the DerSimonian and Laird random-effects model, weighted by inverse variance. The diamond represents a pooled estimate of the annual rate of change across studies within each disease type. Abbreviations: CI, confidence interval; CMT, Charcot-Marie-Tooth disease; DPN, diabetic peripheral neuropathy; ATTRv-PN, hereditary transthyretin amyloidosis with polyneuropathy; NIS, Neuropathy Impairment Score; PI: principal investigator

Fig. 4

Weighted Mean Annual Rate of Change of NIS-LL Total Score in Studies of Patients with DPN and ATTRv-PN. Pooled effect estimates were calculated based on the DerSimonian and Laird random-effects model, weighted by inverse variance. The diamond represents a pooled estimate of the annual rate of change across studies within disease type. Abbreviations: CI, confidence interval; DPN, diabetic peripheral neuropathy; ATTRv-PN, hereditary transthyretin amyloidosis with polyneuropathy; NIS-LL, Neuropathy Impairment Score – Lower Limbs; PI: principal investigator