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Orphanet Journal of Rare Diseases

Open Access

Diflunisal in late-onset FAP patients with moderate to severe neuropathy

  • Laura Obici1,
  • Andrea Cortese2,
  • Stefano Perlini3,
  • Alessandro Lozza4,
  • Simona Casarini1,
  • Enrico Alfonsi4 and
  • Giampaolo Merlini1
Orphanet Journal of Rare Diseases201510(Suppl 1):O24

https://doi.org/10.1186/1750-1172-10-S1-O24

Published: 2 November 2015

Keywords

CardiomyopathyDisease DurationPolyneuropathyClose MonitoringCardiac Toxicity

Background

TTR stabilizers have proved effective in slowing neurological progression in FAP. However, wider experience outside trials is required to further establish their safety profile and clinical benefit in the general FAP population.

Objective

We evaluated the safety and efficacy of diflunisal (250 mg BID) in late-onset FAP patients with moderate to severe neuropathy and cardiomyopathy treated for at least 24 months.

Methods

Evaluations included Kumamoto score, polyneuropathy disability score (PND), mBMI, echocardiography and cardiac biomarkers. Adverse events were monitored every three months. Response was evaluated every 12 months.

Results

24 patients (20 males) affected by FAP associated with 7 different mutations were treated for a median of 24 months (range 12-60). Median age at baseline was 69 years (range 57-82), disease duration 43 months (range 17-90), PND score IIIA (range I-IV), Kumamoto score 25 (2-39), BMI 890 (range 604-1458). 21 patients presented with heart involvement. Median NT-proBNP was 728 pg/ml (range 141-5965), cTnI 0.04 ng/ml (range 0.029-0.65), mLVW 14.2 mm (range 12.5-17.5).

PND increased by 1 point from baseline in 8/18 patients. mBMI remained stable during treatment. Mean change in Kumamoto score was 2.9/year (95% CI -0.3 to 4.8). Cardiac progression occurred only in 2/21 patients. One patient discontinued due to renal failure and three presented with a mild increase in serum creatinine. One patient discontinued after 3 years of treatment due to asymptomatic TnI increase that improved following discontinuation. No GI events were recorded.

Conclusion

Our results are consistent with the reported beneficial effect of this drug on neurological progression and suggest a favourable impact also on cardiac disease. Potential renal and cardiac toxicity deserves close monitoring.

Authors’ Affiliations

(1)
Fondazione IRCCS Policlinico San Matteo, Amyloidosis Research and Treatment Center, Pavia, Italy
(2)
General Neurology, Fondazione IRCCS Istituto Neurologico Mondino, Pavia, Italy
(3)
Clinica Medica II, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
(4)
Neurophysiopathology Unit, Fondazione IRCCS Istituto Neurologico Mondino, Pavia, Italy

Copyright

© Obici et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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