Post Hoc Analysis of Nutritional Status in Patients with Transthyretin Familial Amyloid Polyneuropathy: Impact of Tafamidis

Suhr, Ole B.; Conceição, Isabel; Karayal, Onur N.; Mandel, Francine S.; Huertas, Pedro E.; Ericzon, Bo‐Göran

doi:10.1007/s40120-014-0023-8

Cited by 25 publications

(24 citation statements)

References 32 publications

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“…Compared with the worsening observed during the 18-month placebo phase, TQOL remained relatively stable during long-term tafamidis treatment in ATTRV30M patients and was comparable to that observed in the patients who had received tafamidis from study start. Nutritional status as assessed by mBMI remained relatively stable during long-term tafamidis treatment, which is consistent with published analyses by Suhr et al [33], and lends further support for the long-term efficacy of tafamidis in slowing disease progression.…”

Section: Discussionsupporting

confidence: 88%

Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years

Barroso

Judge

Ebede

et al. 2017

Amyloid

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Background: The objective of the present study was to evaluate the long-term safety and efficacy of tafamidis in treating hereditary transthyretin amyloid polyneuropathy. Methods: A prospectively planned interim analysis was conducted on an on-going, phase III, open-label extension study following an 18-month, randomized, controlled study and 12-month, open-label extension study in ATTRV30M patients and a single-arm, open-label study in non-ATTRV30M patients. Thirtyseven ATTRV30M patients received placebo for 18 months, then switched to tafamidis and 38 ATTRV30M patients and 18 non-ATTRV30M patients continuously received tafamidis from day 1, up to 6 years. Results: Long-term tafamidis was associated with a favourable safety/tolerability profile, without any unexpected adverse events. Patients initiating tafamidis at the start of the randomized study had less polyneuropathy progression versus those switching to tafamidis following 18 months of placebo and were less likely to progress to the next ambulatory stage after up to 6 years follow-up. In the patients who switched from placebo to tafamidis, polyneuropathy progression and deterioration in quality of life slowed significantly during long-term tafamidis treatment as compared with the previous placebo treatment. In non-ATTRV30M patients, some polyneuropathy progression was observed across all efficacy measures. Conclusions: These data provide evidence for the long-term (up to 6 years) safety and efficacy of tafamidis. ClinicalTrials.gov: NCT00925002

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Section: Discussionsupporting

confidence: 88%

Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years

Barroso

Judge

Ebede

et al. 2017

Amyloid

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“…In 2014, Suhr et al [ 19 ] published a post hoc analysis of a more detailed account of the impact of tafamidis on nutritional status of patients with TTR-FAP enrolled in clinical trials. mBMI was used as a physiological indicator for treated patients as it is closely related to the duration of gastrointestinal disturbances, malabsorption, and survival after LT [ 19 ].…”

Section: Post Hoc Analyses Of Tafamidismentioning

confidence: 99%

“…For previous trials, mBMI was calculated as the product of the BMI and serum albumin concentration [ 19 ]. Height, weight, and albumin were measured during the baseline visit, and weight and serum albumin were measured every 6 months up to month 30.…”

Section: Post Hoc Analyses Of Tafamidismentioning

confidence: 99%

“…The ITT population of 125 patients in the randomized phase of the trial was reduced to 71 patients in the extension study due to reasons previously described. Baseline evaluation of both groups of patients (tafamidis and placebo) showed that 70% presented gastrointestinal symptoms but that mean values of mBMI were normal as the patient groups constituted of only early-stage patients [ 19 ].…”

Section: Post Hoc Analyses Of Tafamidismentioning

confidence: 99%

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A Review of Tafamidis for the Treatment of Transthyretin-Related Amyloidosis

Cruz

Benson

2015

Neurol Ther

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Transthyretin (TTR)-related amyloidosis (ATTR) is a devastating disease which affects a combination of organs including the heart and the peripheral nerves, and which has a fatal outcome if not treated within a average of 10 years. Tafamidis, or 2-(3,5-dichloro-phenyl)-benzoxazole-6-carboxylic acid, selectively binds to TTR with negative cooperativity and kinetically stabilizes wild-type native TTR and mutant TTR; tafamidis therefore has the potential to halt the amyloidogenic cascade initiated by TTR tetramer dissociation, monomer misfolding, and aggregation. The first tafamidis trial, Fx-005, evaluated the effect of 18 months of tafamidis treatment (20 mg once daily) on disease progression, as well as assessing its safety in TTR-FAP Val30Met patients. The secondary objective of this trial was to study the pharmacodynamic stabilization of mutated TTR. Tafamidis proved effective in reducing the progress of neuropathy, and in maintaining the nutritional status and quality of life of stage 1 (able to walk without support) Val3OMet TTR-FAP patients. Furthermore, TTR stabilization was achieved in more than 90% of patients. An extension study, Fx-006, was conducted to determine the long-term safety and tolerability of tafamidis and to assess the efficacy of the drug on slowing disease progression. No significant safety or tolerability issues were noticed. Taken together, the results from both trials indicated that the beneficial effects of tafamidis were sustained over a 30-month period and that starting treatment early is desirable. Results are expected from an extended open-label study but data that have already been presented show that long-term use of tafamidis in Val30Met patients is associated with reduced progression in polyneuropathy. Tafamidis was initially approved for commercial use in Europe in 2011 and has since been approved for use in Japan, Mexico, and Argentina where it is used as a first-line treatment option for patients with early-stage TTR-FAP. Patients should be carefully followed at referral centers to ascertain the individual response to treatment. In cases of discontinuation, liver transplantation and enrollment in clinical trials of novel drugs aimed mostly toward suppression of TTR production are options.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-015-0031-3) contains supplementary material, which is available to authorized users.

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“…Moreover, by month 30 (completion of the open-label extension), placebo patients with 12 months of tafamidis treatment and tafamidis-treated patients with 30 months of treatment both tended to increase mBMI (28 ± 19 kg/m 2 g/l and 16 ± 18 kg/m 2 g/l, respectively). They concluded that mBMI is appropriate to monitor disease progression in patients with TTR-FAP and treatment with tafamidis can maintain or improve nutritional status [54] .…”

Section: Stabilizers Of Ttr Tetramers: Tafamidis and Diflunisalmentioning

confidence: 99%

Transthyretin amyloidosis: an over review

Tanțău

Laszlo

László

2015

Cardiovasc Regen Med

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Amyloidosis is the extracellular deposition of fibrils, these consist of low molecular weight subunits of a variety of serum proteins. The most common familial amyloidosis is caused by the transthyretin protein. People who are born with inherited mutations in the transthyretin gene produce abnormal, ("variant") transthyretin throughout their liver. The clinical manifestations vary, depending upon the particular substitution, but result either in neuropathy, cardiomyopathy, or both. One of the most common hereditary transthyretin amyloid cardiomyopathies is caused by the Val122IIe mutation. Progressive amyloid deposition in the myocardium and/or in the electrical conduction system is responsible for restrictive cardiomyopathy and unpredictable episodes of arrhythmias and/or severe conduction disorders. The vast majority of transthyretin-familial amyloidotic polyneuropathy cases are associated with Val30Met mutation. Progressive sensorimotor and autonomic neuropathy is the main neuropathic feature of transthyretin amyiloidosis. The first step in evaluating a patient with transthyretin amyloidosis consists in establishing the diagnosis and then evaluating the extent of disease. Deposition of amyloid via tissue can be established by Congo red staining of biopsy specimens. In all cases, amyloid typing has to be completed by transthyretin gene sequencing and by immunofixation electrophoresis of serum and urine. Current treatment options for patients with transthyretin amyiloidosis are limited. Patients with transthyretin-primary familial amyloidosis with mild or moderate disease, a diagnosis confirmed by genetic testing and biopsy, liver transplant is the current treatment standard.

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Post Hoc Analysis of Nutritional Status in Patients with Transthyretin Familial Amyloid Polyneuropathy: Impact of Tafamidis

Cited by 25 publications

References 32 publications

Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years

Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years

A Review of Tafamidis for the Treatment of Transthyretin-Related Amyloidosis

Transthyretin amyloidosis: an over review

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