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Meta-Analysis
. 2021 Feb 12;21(1):70.
doi: 10.1186/s12883-021-02094-y.

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

Xiaochen Lin  1 , Aaron Yarlas  2 , Montserrat Vera-Llonch  3 , Nishtha Baranwal  2 , Josh Biber  2 , Duncan Brown  3 , Braden Vogt  4 , Chafic Karam  4   5
Affiliations
Meta-Analysis

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

Xiaochen Lin et al. BMC Neurol. .

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 Our study also included unpublished data from a clinical registry of patients who were diagnosed with different peripheral neuropathies and seen at the Oregon Health & Science University (OHSU)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.

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Conflict of interest statement

XL, AY, NB, and JB are employees of QualityMetric, which received funding from Akcea Therapeutics for conducting this research. MVL and DB are employees of and own stock in Akcea Therapeutics. CK has received support from Acceleron, Akcea Therapeutics, Alexion, Alnylam, Biogen, Cytokinetics, CSL Behring, and Sanofi Genzyme. BV declares no conflict of interest.

Figures

Fig. 1
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
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
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
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
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