Open access

Research Article

22 August 2022

Clinical manifestations and healthcare utilization before diagnosis of transthyretin amyloidosis

Authors: Jose Nativi-Nicolau https://orcid.org/0000-0002-5481-2122 [email protected], Nowell M Fine, José Thomás Ortiz-Pérez, Duncan Brown, Montserrat Vera-Llonch, Sheila R Reddy https://orcid.org/0000-0002-3911-5943, Eunice Chang https://orcid.org/0000-0003-0177-6153, and Marian H TarboxAuthor Info & Affiliations

Publication: Journal of Comparative Effectiveness Research

Volume 11, Number 14

https://doi.org/10.2217/cer-2022-0074

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Abstract

Introduction: Initial clinical manifestations of transthyretin amyloidosis (ATTR) are not well understood, making timely diagnosis challenging. Methods: Patients aged ≥68 years newly diagnosed with ATTR were identified using Medicare Research Identifiable Files. Symptom manifestation and healthcare utilization were measured during 3 years pre-diagnosis; demographics and comorbidity index during 1-year pre-diagnosis. Controls (ATTR-free) were matched 1:1 to patients with ATTR based on age, sex and region; same index date and enrollment as match. Results: We identified 552 matched ATTR-control pairs: mean age 78.3 (standard deviation 6.3) and 64.5% male. Among patients with ATTR (vs controls), cardiovascular conditions (92.9 vs 75.9%) and hospitalization (54.0 vs 35.5%) were frequent during 3 years pre-diagnosis. Conclusion: Patients with ATTR have multiple symptoms and hospitalizations pre-diagnosis, recognition of which may facilitate earlier diagnosis and treatment.

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References

1.

Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J. Neurol. Neurosurg. Psychiatry 86(9), 1036–1043 (2015).

2.

Ihse E, Ybo A, Suhr O et al. Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis. J. Pathol. 216(2), 253–261 (2008).

3.

Gertz MA, Mauermann ML, Grogan M, Coelho T. Advances in the treatment of hereditary transthyretin amyloidosis: a review. Brain Behav. 9(9), e01371 (2019).

4.

Nakagawa M, Sekijima Y, Yazaki M et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid 23(1), 58–63 (2016).

5.

Coelho T, Maurer MS, Suhr OB. THAOS – The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr. Med. Res. Opin. 29(1), 63–76 (2013).

6.

Swiecicki PL, Zhen DB, Mauermann ML et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid 22(2), 123–131 (2015).

7.

Lane T, Fontana M, Martinez-Naharro A et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation 140(1), 16–26 (2019).

8.

Ruberg FL, Grogan M, Hanna M et al. Transthyretin amyloid cardiomyopathy. J. Am. Coll. Cardiol. 73(22), 2872–2891 (2019).

9.

Reddy SR, Chang E, Tarbox MH et al. The clinical and economic burden of newly diagnosed hereditary transthyretin (ATTRv) amyloidosis: a retrospective analysis of claims data. Neurol. Ther. 9(2), 473–482 (2020).

10.

Stewart M, Shaffer S, Murphy B et al. Characterizing the high disease burden of transthyretin amyloidosis for patients and caregivers. Neurol. Ther. 7(2), 349–364 (2018).

11.

Keohane D, Schwartz J, Gundapaneni B et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid 24(1), 30–36 (2017).

12.

Maurer MS, Schwartz JH, Gundapaneni B et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N. Engl. J. Med. 379(11), 1007–1016 (2018).

13.

Benson MD, Waddington-Cruz M, Berk JL et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N. Engl. J. Med. 379(1), 22–31 (2018).

14.

Adams D, Gonzalez-Duarte A, O'Riordan WD et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379(1), 11–21 (2018).

15.

Castaño A, Helmke S, Alvarez J et al. Diflunisal for ATTR cardiac amyloidosis. Congest. Heart Fail. Greenwich Conn 18(6), 315–319 (2012).

16.

Fox JC, Hellawell JL, Rao S et al. First-in-human study of AG10, a novel, oral, specific, selective, and potent transthyretin stabilizer for the treatment of transthyretin amyloidosis: a phase 1 safety, tolerability, pharmacokinetic, and pharmacodynamic study in healthy adult volunteers. Clin. Pharmacol. Drug Dev. 9(1), 115–129 (2020).

17.

Vera-Llonch M, Reddy SR, Chang E et al. The patient journey toward a diagnosis of hereditary transthyretin (ATTRv) amyloidosis. Orphanet J. Rare Dis. 16(1), 25 (2021).

18.

Centers for Medicare & Medicaid Services. On its 50th anniversary, more than 55 million Americans covered by Medicare (2015). www.cms.gov/newsroom/press-releases/its-50th-anniversary-more-55-million-americans-covered-medicare

19.

Virnig B. Strengths and Limitations of CMS Administrative Data in Research (2018). www.resdac.org/articles/strengths-and-limitations-cms-administrative-data-research

20.

Siedelman L. Differences between RIF, LDS, and PUF Data Files (2016). www.resdac.org/articles/differences-between-rif-lds-and-puf-data-files

21.

Ghiso J, Frangione B. Cerebral amyloidosis, amyloid angiopathy, and their relationship to stroke and dementia. J. Alzheimers Dis. 3(1), 65–73 (2001).

22.

Keage HA, Carare RO, Friedland RP et al. Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol. 9(1), 3 (2009).

23.

Chen S-J, Tsai H-H, Tsai L-K et al. Advances in cerebral amyloid angiopathy imaging. Ther. Adv. Neurol. Disord. 12, 1756286419844113 (2019).

24.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40(5), 373–383 (1987).

25.

Agency for Healthcare Research and Quality. HCUP Chronic Condition Indicator (2015). www.hcup-us.ahrq.gov/toolssoftware/chronic/chronic.jsp

26.

ResDAC, Waruiru Mburu. CMS Cell Size Suppression Policy (2017). https://resdac.org/articles/cms-cell-size-suppression-policy

27.

Nativi-Nicolau JN, Karam C, Khella S, Maurer MS. Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail. Rev. (2021).

28.

Lousada I, Maurer MS, Warner MT et al. Amyloidosis research consortium cardiac amyloidosis survey: results from patients with AL and ATTR amyloidosis and their caregivers. J. Card. Fail. 25(8), S69 (2019).

29.

Witteles RM, Bokhari S, Damy T et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 7(8), 709–716 (2019).

30.

Maurer MS, Elliott P, Comenzo R et al. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation 135(14), 1357–1377 (2017).

31.

Schmidt H, Lin H, Agarwal S et al. Impact of hereditary transthyretin-mediated amyloidosis on use of health care services: an analysis of the APOLLO study. Presented at: The 16th International Symposium on Amyloidosis (ISA). Kumamoto, Japan, 26–29 March 2018.

32.

Sperry BW, Saeed IM, Raza S et al. Increasing rate of hospital admissions in patients with amyloidosis (from the National Inpatient Sample). Am. J. Cardiol. 124(11), 1765–1769 (2019).

33.

Tyree PT, Lind BK, Lafferty WE. Challenges of using medical insurance claims data for utilization analysis. Am. J. Med. Qual. Off. J. Am. Coll. Med. Qual. 21(4), 269–275 (2006).

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