114 results on '"Biegstraaten M"'
Search Results
2. Hearing loss in children with Fabry disease
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Suntjens, E., Dreschler, W. A., Hess-Erga, J., Skrunes, R., Wijburg, F. A., Linthorst, G. E., Tøndel, C., and Biegstraaten, M.
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- 2017
- Full Text
- View/download PDF
3. Factors Contributing to the Efficacy-Effectiveness Gap in the Case of Orphan Drugs for Metabolic Diseases
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Schuller, Y., Hollak, C. E. M., Gispen-de Wied, C. C., Stoyanova-Beninska, V., and Biegstraaten, M.
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- 2017
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- View/download PDF
4. Uncertain diagnosis of Fabry disease: Consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance
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Smid, B.E., van der Tol, L., Cecchi, F., Elliott, P.M., Hughes, D.A., Linthorst, G.E., Timmermans, J., Weidemann, F., West, M.L., Biegstraaten, M., Lekanne Deprez, R.H., Florquin, S., Postema, P.G., Tomberli, B., van der Wal, A.C., van den Bergh Weerman, M.A., and Hollak, C.E.
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- 2014
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5. A monozygotic twin pair with highly discordant Gaucher phenotypes
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Biegstraaten, M., van Schaik, I.N., Aerts, J.M.F.G., Langeveld, M., Mannens, M.M.A.M., Bour, L.J., Sidransky, E., Tayebi, N., Fitzgibbon, E., and Hollak, C.E.M.
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- 2011
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6. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance
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van der Tol, L, Smid, B E, Poorthuis, B J H M, Biegstraaten, M, Deprez, R H Lekanne, Linthorst, G E, and Hollak, C E M
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- 2014
- Full Text
- View/download PDF
7. ‘Non-neuronopathic’ Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature
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Biegstraaten, M., van Schaik, I. N., Aerts, J. M. F. G., and Hollak, C. E. M.
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- 2008
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8. Biceps Rerouting after Forearm Osteotomy: An Effective Treatment Strategy for Severe Supination Deformity in Obstetric Plexus Palsy
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Metsaars, W., primary, Biegstraaten, M., primary, and Nelissen, R., primary
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- 2017
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9. Position statement on the role of healthcare professionals, patient organizations and industry in European Reference Networks
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Hollak, C.E., Biegstraaten, M., Baumgartner, M.R., Belmatoug, N., Bembi, B., Bosch, A. van den, Brouwers, M., Dekker, H., Dobbelaere, D., Engelen, M., Groenendijk, M.C., Lachmann, R., Langendonk, J.G., Langeveld, M., Linthorst, G., Morava, E., Poll-The, B.T., Rahman, S., Rubio-Gozalbo, M.E., Spiekerkoetter, U., Treacy, E., Wanders, R., Zschocke, J., Hagendijk, R., Hollak, C.E., Biegstraaten, M., Baumgartner, M.R., Belmatoug, N., Bembi, B., Bosch, A. van den, Brouwers, M., Dekker, H., Dobbelaere, D., Engelen, M., Groenendijk, M.C., Lachmann, R., Langendonk, J.G., Langeveld, M., Linthorst, G., Morava, E., Poll-The, B.T., Rahman, S., Rubio-Gozalbo, M.E., Spiekerkoetter, U., Treacy, E., Wanders, R., Zschocke, J., and Hagendijk, R.
- Abstract
Contains fulltext : 171214.pdf (publisher's version ) (Open Access), A call from the EU for the set-up of European Reference Networks (ERNs) is expected to be launched in the first quarter of 2016. ERNs are intended to improve the care for patients with low prevalent or rare diseases throughout the EU by, among other things, facilitating the pooling and exchange of experience and knowledge and the development of protocols and guidelines. In the past, for example where costly orphan drugs have been concerned, industry has played an important role in facilitating consensus meetings and publication of guidelines. The ERNs should provide a unique opportunity for healthcare professionals and patients to lead these activities in an independent way. However, currently costs for networking activities are not to be covered by EU funds and alternative sources of funding are being explored. There is growing concern that any involvement of the industry in the funding of ERNs and their core activities may create a risk of undue influence. To date, the European Commission has not been explicit in how industry will be engaged in ERNs. We believe that public funding and a conflict of interest policy are needed at the level of the ERNs, Centers of Expertise (CEs), healthcare professionals and patient organizations with the aim of maintaining scientific integrity and independence. Specific attention is needed where it concerns the development of clinical practice guidelines. A proposal for a conflict of interest policy is presented, which may support the development of a framework to facilitate collaboration, safeguard professional integrity and to establish and maintain public acceptability and trust among patients, their organizations and the general public.
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- 2016
10. Position statement on the role of healthcare professionals, patient organizations and industry in European Reference Networks
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Hollak, C.E.M. (Carla), Biegstraaten, M. (Marieke), Baumgartner, M.R. (Matthias R.), Belmatoug, N. (Nadia), Bembi, B. (Bruno), Bosch, A.M. (Annet), Brouwers, M.C.G.J. (M. C G J), Dekker, H. (Hanka), Dobbelaere, D. (Dries), Engelen, M. (Marc), Groenendijk, M.C. (Marike C.), Lachmann, R.H. (Robin), Langendonk, J.G. (Janneke), Langeveld, M. (Mirjam), Linthorst, G. (Gabor), Morava, E. (Eva), Poll-The, B.T., Rahman, S. (Shamima), Rubio-Gozalbo, M.E. (Estela), Spiekerkoeter, U. (Ute), Treacy, E. (Eileen), Wanders, R.J.A. (Ronald), Zschocke, J. (Johannes), Hagendijk, R. (Rob), Hollak, C.E.M. (Carla), Biegstraaten, M. (Marieke), Baumgartner, M.R. (Matthias R.), Belmatoug, N. (Nadia), Bembi, B. (Bruno), Bosch, A.M. (Annet), Brouwers, M.C.G.J. (M. C G J), Dekker, H. (Hanka), Dobbelaere, D. (Dries), Engelen, M. (Marc), Groenendijk, M.C. (Marike C.), Lachmann, R.H. (Robin), Langendonk, J.G. (Janneke), Langeveld, M. (Mirjam), Linthorst, G. (Gabor), Morava, E. (Eva), Poll-The, B.T., Rahman, S. (Shamima), Rubio-Gozalbo, M.E. (Estela), Spiekerkoeter, U. (Ute), Treacy, E. (Eileen), Wanders, R.J.A. (Ronald), Zschocke, J. (Johannes), and Hagendijk, R. (Rob)
- Abstract
A call from the EU for the set-up of European Reference Networks (ERNs) is expected to be launched in the first quarter of 2016. ERNs are intended to improve the care for patients with low prevalent or rare diseases throughout the EU by, among other things, facilitating the pooling and exchange of experience and knowledge and the development of protocols and guidelines. In the past, for example where costly orphan drugs have been concerned, industry has played an important role in facilitating consensus meetings and publication of guidelines. The ERNs should provide a unique opportunity for healthcare professionals and patients to lead these activities in an independent way. However, currently costs for networking activities are not to be covered by EU funds and alternative sources of funding are being explored. There is growing concern that any involvement of the industry in the funding of ERNs and their core activities may create a risk of undue influence. To date, the European Commission has not been explicit in how industry will be engaged in ERNs. We believe that public funding and a conflict of interest policy are needed at the level of the ERNs, Centers of Expertise (CEs), healthcare professionals and patient organizations with the aim of maintaining scientific integrity and independence. Specific attention is needed where it concerns the development of clinical practice guidelines. A proposal for a conflict of interest policy is presented, which may support the development of a framework to facilitate collaboration, safeguard professional integrity and to establish and maintain public acceptability and trust among patients, their organizations and the general public.
- Published
- 2016
- Full Text
- View/download PDF
11. Position statement on the role of healthcare professionals, patient organizations and industry in European Reference Networks
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Hollak, CEM, Biegstraaten, M, Baumgartner, MR, Belmatoug, N, Bembi, B, Bosch, A, Brouwers, M, Dekker, H, Dobbelaere, D, Engelen, M, Groenendijk, M C, Lachmann, R, Langendonk, Janneke, Langeveld, Mirjam, Linthorst, G, Morava, E, Poll-The, BT, Rahman, S, Rubio-Gozalbo, ME, Spiekerkoetter, U, Treacy, E, Wanders, R, Zschocke, J, Hagendijk, R, Hollak, CEM, Biegstraaten, M, Baumgartner, MR, Belmatoug, N, Bembi, B, Bosch, A, Brouwers, M, Dekker, H, Dobbelaere, D, Engelen, M, Groenendijk, M C, Lachmann, R, Langendonk, Janneke, Langeveld, Mirjam, Linthorst, G, Morava, E, Poll-The, BT, Rahman, S, Rubio-Gozalbo, ME, Spiekerkoetter, U, Treacy, E, Wanders, R, Zschocke, J, and Hagendijk, R
- Published
- 2016
12. Erratum to: Pain management strategies for neuropathic pain in Fabry disease - a systematic review
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Schuller, Y., primary, Linthorst, G.E., additional, Hollak, C.E.M., additional, Van Schaik, I.N., additional, and Biegstraaten, M., additional
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- 2016
- Full Text
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13. Pain management strategies for neuropathic pain in Fabry disease - a systematic review
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Schuller, Y., primary, Linthorst, G. E., additional, Hollak, C. E. M., additional, Van Schaik, I. N., additional, and Biegstraaten, M., additional
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- 2016
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14. Neurological aspects of Gaucher and Fabry disease
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Biegstraaten, M., van Schaik, I.N., Hollak, C.E.M., Aerts, Johannes M.F.G., Faculteit der Geneeskunde, van Schaik, Ivo N., Hollak, Carolina E. M., Aerts, Johannes M. F. G., and Neurology
- Abstract
Momenteel zijn er meer dan vijftig stapelingsziekten bekend, waarvan de ernst zeer uiteen loopt. Sommige aandoeningen worden gekenmerkt door ernstige mentale retardatie, neurologische problemen en overlijden op kinderleeftijd; andere vormen hebben nauwelijks een lagere levensverwachting. Ook in de laatste groep kunnen neurologische complicaties optreden, die soms hinderlijk en zelfs invaliderend zijn. Marieke Biegstraaten onderzocht de ernst en het beloop van neurologische complicaties bij volwassen patiënten met de ziekte van Gaucher type I en de ziekte van Fabry. Eerstgenoemde groep heeft veel neurologische aandoeningen, hoewel dit interessant genoeg niet altijd tot problemen in het dagelijks leven leidt. Patiënten met de ziekte van Fabry hebben vaak pijn- en koude-ongevoeligheid. Het autonome zenuwstelsel blijft hierbij gespaard.
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- 2011
15. The quality of economic evaluations of ultra-orphan drugs in Europe – a systematic review
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Schuller, Y., primary, Hollak, C. E. M., additional, and Biegstraaten, M., additional
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- 2015
- Full Text
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16. Uncertain diagnosis of fabry disease in patients with neuropathic pain, angiokeratoma or cornea verticillata: consensus on the approach to diagnosis and follow-up
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Tol, L. van der, Cassiman, D., Houge, G., Janssen, M.C., Lachmann, R.H., Linthorst, G.E., Ramaswami, U., Sommer, C., Tondel, C., West, M.L., Weidemann, F., Wijburg, F.A., Svarstad, E., Hollak, C.E.M., Biegstraaten, M., Tol, L. van der, Cassiman, D., Houge, G., Janssen, M.C., Lachmann, R.H., Linthorst, G.E., Ramaswami, U., Sommer, C., Tondel, C., West, M.L., Weidemann, F., Wijburg, F.A., Svarstad, E., Hollak, C.E.M., and Biegstraaten, M.
- Abstract
Item does not contain fulltext, INTRODUCTION: Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the alpha-galactosidase A (GLA) gene may be unclear. This uncertainty often leads to considerable distress and inappropriate counselling and treatment. We developed a clinical approach for these individuals with an uncertain diagnosis of FD. MATERIALS AND METHODS: A document was presented to an FD expert panel with background information based on clinical experience and the literature, followed by an online survey and a written recommendation. RESULTS: The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain, AK and/or CV only, i.e. without kidney, heart or brain disease, with an uncertain diagnosis of FD. Only in the presence of FD-specific neuropathic pain (small fibre neuropathy with FD-specific pattern), AK (FD-specific localisations) or CV (without CV inducing medication), FD is confirmed. When these features have a non-specific pattern, there is insufficient evidence for FD. If no alternative diagnosis is found, follow-up is recommended. CONCLUSIONS: In individuals with an uncertain diagnosis of FD, the presence of an FD-specific pattern of CV, AK or neuropathic pain is sufficient to confirm the diagnosis of FD. When these features are non-specific, a definite diagnosis cannot (yet) be established and follow-up is indicated. ERT should be considered only in those patients with a confirmed diagnosis of FD.
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- 2014
17. Niet-invasieve beademing goede optie bij amyotrofische laterale sclerose
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Biegstraaten, M., Van Der Kooi, A. J., Graduate School, Neurology, Amsterdam Gastroenterology Endocrinology Metabolism, and Amsterdam Neuroscience
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- 2007
18. Pregabaline bij de behandeling van neuropathische pijn
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Biegstraaten, M., van Schaik, I. N., Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Neuroscience, Neurology, and Amsterdam institute for Infection and Immunity
- Abstract
Pregabalin is increasingly being used for the treatment ofneuropathic pain, often as the first-line choice. The question is, however, whether this choice is based on evidence. Seven trials have been published on the effect ofpregabalin in patients with postherpetic neuralgia and painful diabetic neuropathy. These trials more frequently report a 50% reduction in pain in pregabalin treated patients than in patients treated with placebo (number needed to treat 4.3). Dizziness and somnolence are the most frequent adverse events of pregabalin. The number needed to harm for adverse events leading to discontinuation of treatment varies from 3.7 to 113.1 in these studies. Pregabalin has not been compared head-to-head with other drugs commonly used for neuropathic pain. Indirect comparison reveals the effectiveness of pregabalin is comparable with that of carbamazepin, tramadol, and gabapentin; pregabalin is possibly less effective than amitriptylin. However, taking into account its price and the lack of clinical experience and evidence, using pregabalin as first-line choice is not recommended
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- 2007
19. The role of object contact in pointing and grasping
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Biegstraaten, M (Marianne), Borst, Gerard, and Neurosciences
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- 2005
20. FabryScan —/INS; A screening tool for Fabry disease
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Höper, J., primary, Naleschinski, D., additional, Arning, K., additional, Maag, R., additional, Biegstraaten, M., additional, Kropp, P., additional, Lorenzen, J., additional, Hollak, C.E.M., additional, van Schaik, I.N., additional, Harten, P., additional, Zeuner, R.A., additional, Binder, A., additional, and Baron, R., additional
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- 2013
- Full Text
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21. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance
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van der Tol, L, primary, Smid, B E, additional, Poorthuis, B J H M, additional, Biegstraaten, M, additional, Deprez, R H Lekanne, additional, Linthorst, G E, additional, and Hollak, C E M, additional
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- 2013
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22. 49 A prospective study of neurological manifestations and other comorbidities in adult type I Gaucher disease
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Hollak, C.E.M., primary, Marodi, L., additional, Biegstraaten, M., additional, Van Schaik, I.N., additional, Niederau, C., additional, Hughes, D., additional, Giraldo, P., additional, and Beck, M., additional
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- 2007
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23. P03. Saccadic eye movement abnormalities in children with type 3 Gaucher disease are indicative for brainstem reticular formation pathology
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Bour, L., primary, Cox-Brinkman, J., additional, Biegstraaten, M., additional, and van Rootselaar, A. Fleur, additional
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- 2007
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24. WITHDRAWN: 82 A prospective study of neurological manifestations and other comorbidities in adult type I Gaucher disease
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Niederau, C., primary, Hollak, C.E.M., additional, Hughes, D., additional, Van Schaik, I.N., additional, Marodi, L., additional, Beck, M., additional, Biegstraaten, M., additional, and Giraldo, P., additional
- Published
- 2007
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25. The quality of economic evaluations of ultraorphan drugs in Europe - a systematic review.
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Schuller, Y., Hollak, C. E. M., and Biegstraaten, M.
- Subjects
ORPHAN drugs ,DRUG prices ,MEDICAL care costs ,LYSOSOMAL storage diseases ,QUALITY of life ,GAUCHER'S disease ,ECULIZUMAB ,META-analysis - Abstract
An orphan disease is defined in the EU as a disorder affecting less than 1 in 2 000 individuals. The concept of ultra-orphan has been proposed for diseases with a prevalence of less than 1:50 000. Drugs for ultra-orphan diseases are amongst the most expensive medicines on a cost-per-patient basis. The extremely high prices have prompted initiatives to evaluate cost-effectiveness and cost-utility in EU-member states. The objective of this review was to evaluate the quality of cost-effectiveness and cost-utility studies on ultra-orphan drugs. We searched 2 databases and the reference lists of relevant systematic reviews. Studies reporting on full economic evaluations, or at least aiming at such evaluation, were eligible for inclusion. Quality was assessed with the use of the Consensus on Health Economic Criteria (CHEC)-list. Two-hundred-fifty-one studies were identified. Of these, 16 fitted our inclusion criteria. A study on enzyme replacement and substrate reduction therapies for lysosomal storage disorders did not perform a full economic evaluation due to the high drug costs and the lack of a measurable effect on either clinical or health-related quality of life outcomes. Likewise, a cost-effectiveness analysis of laronidase for mucopolysaccharidosis type 1 was considered unfeasible due to lack of clinical effectiveness data, while in the same study a crude model was used to estimate cost-utility of enzyme replacement therapy (ERT) for Fabry disease. Three additional studies, one on ERT for Fabry disease, one on ERT for Gaucher disease and one on eculizumab for paroxysmal nocturnal haemoglobinuria, used an approach that was too simplistic to lead to a realistic estimate of the incremental cost-effectiveness (ICER) or cost-utility ratio (ICUR). In all other studies (N = 11) more sophisticated pharmacoeconomic models were used to estimate cost-effectiveness and cost-utility of the specific drug, mostly ERT or drugs indicated for pulmonary arterial hypertension (PAH). Seven studies used a Markov-state-transition model. Other models used were patient-level simulation models (N = 3) and decision trees (N = 1). Only 4 studies adopted a societal perspective. All but 2 studies discounted costs and effects appropriately. Drugs for metabolic diseases appeared to be significantly less cost-effective than drugs indicated for PAH, with ICERs ranging from €43 532 (Gaucher disease) to €3 282 252 (Fabry disease). Quality of studies using a Markov-state-transition or patient-level simulation model is in general good with 14-19 points on the CHEC-list. We therefore conclude that economic evaluations of ultra-orphan drugs are feasible if pharmacoeconomic modelling is used. Considering the need for modelling of several disease states and the small patient groups, a Markov-state-transition model seems to be most suitable type of model. However, it should be realised that ultra-orphan drugs will usually not meet the conventional criteria for cost-effectiveness. Nevertheless, ultra-orphan drugs are often reimbursed. Further discussion on the use of economic evaluations and their consequences in case of ultra-orphan drugs is therefore warranted. [ABSTRACT FROM AUTHOR]
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- 2015
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26. The Ebbinghaus figure is more than a size illusion
- Author
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Grave, D. D. J., primary, Biegstraaten, M., additional, Brenner, E., additional, and Smeets, J. B. J., additional
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- 2004
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27. Determining the optimal flexion–extension axis of the elbow in vivo — a study of interobserver and intraobserver reliability
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Stokdijk, M, primary, Biegstraaten, M, additional, Ormel, W, additional, de Boer, Y.A, additional, Veeger, H.E.J, additional, and Rozing, P.M, additional
- Published
- 2000
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28. The relation between small nerve fibre function, age, disease severity and pain in Fabry disease.
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Biegstraaten M, Binder A, Maag R, Hollak CE, Baron R, and van Schaik IN
- Abstract
BACKGROUND: Small fibre neuropathy supposedly causes pain in Fabry patients, but the relationship between small nerve fibre function and pain severity is unclear. METHODS: A cohort of 15 male and 33 female Fabry patients was studied making use of a quantitative sensory testing protocol, disease severity measures and pain scales to investigate the relationship between nerve fibre function, age, disease severity and pain intensity. RESULTS: Male Fabry patients exhibited an abnormal cold detection threshold and thermal sensory limen at the upper and lower limb, indicating A[delta]-fibre hypofunction. Female patients showed Z-scores within normal range for all modalities. Nerve fibre function was worse at older age and with more severe disease. The overall severity of pain was mild, without significant differences between males and females. No linear relationship between pain severity and small nerve fibre function was identified. CONCLUSIONS: In Fabry disease, no linear relationship exists between pain and small nerve fibre function. With older age and more severe disease pain may abate as nerve fibre function further deteriorates. [ABSTRACT FROM AUTHOR]
- Published
- 2011
29. Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests
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Wijburg Frits A, Wieling Wouter, van Schaik Ivo N, Biegstraaten Marieke, and Hollak Carla EM
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients. Methods Forty-eight Fabry patients (15 male, 30 treated with enzyme replacement therapy) and 48 sex- and age-matched controls completed a questionnaire on autonomic symptoms (the Autonomic Symptom Profile). Thirty-six Fabry patients underwent cardiovascular function tests. Results The Autonomic Symptom Profile revealed a significantly higher sum score in Fabry patients than in healthy control subjects (22 versus 12), but a relatively low score compared to patients with proven autonomic neuropathy. Fabry patients scored worse than healthy controls in the orthostatic intolerance domain. Scores in the male sexual dysfunction domain were comparable between healthy controls and male Fabry patients. The cardiovascular autonomic function tests revealed only mild abnormalities in seven patients. None of these seven patients showed more than one abnormal test result. Enzyme replacement therapy was not associated with less severe disease, lower ASP scores or less frequent abnormal cardiovascular function test results. Conclusions Male sexual function and autonomic control of the cardiovascular system are nearly normal in Fabry patients, which cast doubt on the general accepted assumption that autonomic neuropathy is the main cause of symptoms and signs compatible with autonomic dysfunction in Fabry disease. Possibly, end-organ damage plays a key role in the development of symptoms and signs in Fabry patients. An exceptional kind of autonomic neuropathy is another but less likely explanation.
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- 2010
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30. Mind the gap: Bridging the difference between efficacy and effectiveness of orphan drugs
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Schuller, Yvonne, Hollak, C.E.M., Biegstraaten, M., Stoyanova-Beninska, V.V., Faculteit der Geneeskunde, Hollak, Carolina E. M., Biegstraaten, Marieke, Stoyanova-Beninska, V. V., Endocrinology, Graduate School, and AGEM - Inborn errors of metabolism
- Abstract
In the European Union, a disease is called ‘orphan’ if it is a disorder that affects fewer than 5 per 10.000 of the population. Authorization of orphan drugs is often based on studies with several methodological shortcomings. Because of this, longer term effectiveness on clinically relevant outcome measures is often unclear at the time of authorization and some drugs that enter the market, may not be effective in the real-world. The aim of this thesis was to study the presence of a so-called efficacy-effectiveness gap of orphan drugs, and the factors that possibly contribute to it. We confirmed that indeed a gap exists in the case of orphan drugs for metabolic diseases and oncology. The most important factor that contributed to this gap was the type of primary endpoint used in the pivotal study. This information may be used when conducting future studies on orphan diseases. Furthermore, we showed that dose-finding studies in the case of metabolic and oncologic orphan drugs are not always conducted in the development program, while post-marketing evidence suggests that registered doses are not always considered as optimal. Also, we elaborated on how an adaptive pathway approach could have benefitted the development of enzyme replacement therapy for Fabry disease in several ways, including 1) iterative development, 2) an independent disease registry with independent data analysis and 3) prescription control. In conclusion, this thesis will contribute to an important discussion on the real-world effectiveness of orphan drugs.
- Published
- 2018
31. Enzyme replacement therapy in Fabry disease, towards individualized treatment
- Author
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Arends, M., Hollak, Carolina E. M., Biegstraaten, Marieke, Graduate School, Amsterdam Gastroenterology Endocrinology Metabolism, Hollak, C.E.M., Biegstraaten, M., and Faculteit der Geneeskunde
- Abstract
Fabry disease is a very heterogeneous disorder for which expensive enzyme replacement therapy is available since more than 15 years. Because of the variety of symptoms and disease course, individual choices need to be made to improve the appropriate use of therapy. Supported by ZONWM, we have been able to create a unique, independent, database, of almost 600 Fabry disease patients from three European Fabry disease centers of excellence. The aim of this thesis was to describe the differences in the disease course between treated and untreated male and female patients with a classical or a non-classical phenotype and the effects of two different enzymes. We established that phenotype (classical or non-classical) and gender were major determinants for the disease severity in untreated patients. This crucial information could then be used to study effects of enzyme replacement therapy, showing that, after adjustment for gender, phenotype and age, we could identify risk factors for disease progression, including renal function at baseline, a history of one or more events and left ventricular mass. Importantly, we have also been able to show differences in effect of enzyme replacement therapies, with less immunogenicity of agalsidase alfa, but better biochemical and, albeit limited, clinical improvement for the higher dosed agalsidase beta. In conclusion, the results of this thesis will fuel the discussion on start and stop criteria for enzyme replacement therapy and highlight the importance of phenotype, gender and age in the evaluation of the disease course.
- Published
- 2017
32. Fabry or not Fabry: From genetics to diagnosis
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van der Tol, Linda, Hollak, C.E.M., Linthorst, G.E., Biegstraaten, M., Faculteit der Geneeskunde, Hollak, Carolina E. M., Linthorst, Gabor E., Biegstraaten, Marieke, and Other departments
- Abstract
Fabry disease is a lysosomal storage disorder with an X-linked pattern of inheritance. Fabry disease is caused by impaired degradation and accumulation of the glycosphingolipid globotriaosylceramide, due to a deficiency of the enzyme α-Galactosidase A. Both males and females can be affected, although in general, females demonstrate a more attenuated phenotype. Screening and individual diagnostic testing revealed a higher prevalence than expected of individuals with variants in the Fabry gene. However, while these individuals may have Fabry disease, a variant in the Fabry gene may also be non-pathogenic. This caries the risk of misdiagnosis, inappropriate counseling, and unjustified treatment with expensive enzyme replacement therapy. The aim of this thesis was to improve the diagnosis of Fabry disease, in order to support the diagnostic process in individuals with a genetic variant of unknown significance in the Fabry gene. A literature review on screening for Fabry disease showed that a large number of individuals with a non-specific clinical feature such as cardiac hypertrophy, chronic kidney disease of stroke, do not demonstrate characteristic signs or symptoms as seen in classical Fabry disease. In collaboration with (inter)national experts on Fabry disease we developed diagnostic guidelines to aid in the diagnostic approach for these individuals, using the best available evidence from the literature and additional analyses. Furthermore, we specifically studied the diagnostic value of clinical and biochemical features characteristic of classical Fabry disease.
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- 2015
33. FabryScan —/INS; A screening tool for Fabry disease.
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Anonymous, Naleschinski, D., Arning, K., Maag, R., Biegstraaten, M., Kropp, P., Lorenzen, J., Hollak, C.E.M., van Schaik, I.N., Harten, P., Zeuner, R.A., Binder, A., and Baron, R.
- Published
- 2013
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34. Oncologic orphan drugs approved in the EU - do clinical trial data correspond with real-world effectiveness?
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Schuller Y, Biegstraaten M, Hollak CEM, Klümpen HJ, Gispen-de Wied CC, and Stoyanova-Beninska V
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- Drug Approval, European Union, Humans, Medical Oncology, Orphan Drug Production
- Abstract
Background: Evaluation of evidence for efficacy of orphan medicinal products (OMPs) for rare malignancies may be hampered by the use of tumor measurements instead of clinical endpoints. This may cause efficacy data to not always match effectiveness in the real-world. We investigated whether an efficacy-effectiveness gap exists for oncologic OMPs and aimed to identify which factors contribute to it. Also, the magnitude of the clinical efficacy of oncologic OMPs was evaluated., Methods: We included all oncologic OMPs authorized in the European Union from 2000 to 2017. Pivotal studies were evaluated by means of the European Society for Medical Oncology - Magnitude of Clinical Benefit Scale (ESMO-MCBS). To estimate real-world effectiveness, a literature search was performed to identify post-marketing studies, of which data on overall survival (OS) were extracted. OS of the new OMP was compared with OS data of standard of care. An OS gain of ≥3 months compared to pre-marketing data was considered clinically relevant., Results: Twenty OMPs were included, of which 5 were authorized based on OS as a primary endpoint. 10 OMPs had post-marketing data available, of which 40% did not show a clinically relevant OS gain in the real world. All OMPs that were studied with OS as primary endpoint in the pivotal study had a clinically relevant OS gain in the real world. Furthermore, all OMPs that had a high ESMO-MCBS score and post-marketing data available, resulted in a clinically relevant OS gain in the real world., Conclusions: Although the sample size is small, our results indicate an efficacy-effectiveness gap for oncologic OMPs exists. Significant changes in PFS do not always lead to an increased OS. The use of PFS may be justified, but validation of surrogate endpoints is needed.
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- 2018
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35. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.
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Arends M, Biegstraaten M, Wanner C, Sirrs S, Mehta A, Elliott PM, Oder D, Watkinson OT, Bichet DG, Khan A, Iwanochko M, Vaz FM, van Kuilenburg ABP, West ML, Hughes DA, and Hollak CEM
- Subjects
- Adult, Cohort Studies, Enzyme Replacement Therapy, Fabry Disease genetics, Fabry Disease pathology, Female, Glomerular Filtration Rate drug effects, Humans, Isoenzymes genetics, Male, Middle Aged, Recombinant Proteins genetics, Retrospective Studies, Treatment Outcome, alpha-Galactosidase genetics, Fabry Disease drug therapy, Isoenzymes administration & dosage, Recombinant Proteins administration & dosage, alpha-Galactosidase administration & dosage
- Abstract
Background: Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes., Methods: In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex., Results: 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar., Conclusions: Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta., Competing Interests: Competing interests: CW has received honoraria for lecturing from Sanofi Genzyme (Cambridge, Massachusetts, USA) and a grant to the institution from Sanofi Genzyme and Shire (Dublin, Ireland). SS, DGB, AK, MI and MLW have served on advisory boards, received fees for speaking or travel support and participated in other clinical trials and registries sponsored by Sanofi Genzyme and Shire. MLW has received travel funds, research funds or consultancy fees from Actelion, Alexion, Amicus, Excelsior, GlaxoSmithKline, Protalix and SumitomoPharma. AM has received honoraria for consultancies and educational activities as well as research support from Shire, Sanofi Genzyme, Protalix/Pfizer (New York City, New York, USA) and Amicus. DO has received speakers honoraria from Sanofi Genzyme and travel assistance from Sanofi Genzyme and Shire. PME has received speaker fees from Shire and consultancy and speaker fees from Sanofi Genzyme, Pfizer and Gilead Sciences (Foster City, California, USA). DAH has received honoraria for speaking and participating in advisory boards and support for research from Shire, Sanofi Genzyme, Amicus (Cranbury, New Jersey, USA) and Protalix (Carmiel, Israel). Also, DAH has a consultancy arrangement through UCL Consultants (London, UK) to support, in part, laboratory research. MB and CEMH have received travel support, honoraria for consultancies and educational grants from Sanofi Genzyme, Shire, Protalix, Actelion (Allschwil, Switzerland) and Amicus. All financial arrangements are made with the AMC Medical Research BV in accordance with the Research Code of the Academic Medical Center., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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- 2018
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36. Phenotype, disease severity and pain are major determinants of quality of life in Fabry disease: results from a large multicenter cohort study.
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Arends M, Körver S, Hughes DA, Mehta A, Hollak CEM, and Biegstraaten M
- Subjects
- Adult, Disease Progression, Fabry Disease diagnosis, Fabry Disease genetics, Fabry Disease physiopathology, Female, Humans, London, Male, Middle Aged, Netherlands, Pain diagnosis, Pain genetics, Pain physiopathology, Pain Measurement, Phenotype, Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Factors, Severity of Illness Index, Surveys and Questionnaires, Time Factors, Cost of Illness, Fabry Disease psychology, Pain psychology, Quality of Life
- Abstract
Quality of life (QoL) is decreased in patients with Fabry disease (FD). To improve QoL, it is important to understand the influence of FD related characteristics, symptoms, and complications. In this retrospective cohort study we explored the effect of pain (measured by the Brief Pain Inventory), phenotype, treatment, and FD-related complications on QoL. QoL data of Fabry patients as assessed by the EuroQol five dimension questionnaire (EQ-5D) from two international centers of excellence were collected. The aim of this study was to evaluate the effect of sex, phenotype, age, different states of disease severity, pain, and ERT on EQ-5D utilities. For 286 adult FD patients (mean age 42.5 years, 40% men, 60% classical phenotype) 2240 EQ-5Ds were available. QoL is decreased in men as well as women with FD, especially in older men with a classical phenotype. At age 50, utility was lower in men with classical FD compared to those with non-classical disease (β = -0.12, 95% CI: -0.23 - 0.01, p = 0.037) with further difference in the years thereafter. Cardiovascular complications, stroke or transient ischemic attacks, multiple FD-related complications and pain were also associated with decreased utilities. Overall, no change in utility was seen in patients on ERT over a mean follow-up of 6.1 years. FD leads to a decreased QoL compared to the general population. Disease complications and pain both negatively influence QoL. Adequate assessment and treatment of pain as well as improved strategies to prevent disease complications are needed to improve QoL in the FD population.
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- 2018
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37. Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors.
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Arends M, Biegstraaten M, Hughes DA, Mehta A, Elliott PM, Oder D, Watkinson OT, Vaz FM, van Kuilenburg ABP, Wanner C, and Hollak CEM
- Subjects
- Adolescent, Adult, Aged, Cardiovascular Diseases complications, Comorbidity, Disease Progression, Fabry Disease complications, Female, Glomerular Filtration Rate, Humans, Kidney physiopathology, Male, Middle Aged, Multivariate Analysis, Phenotype, Prognosis, Proportional Hazards Models, Proteinuria complications, Retrospective Studies, Risk Factors, Treatment Outcome, Triglycerides blood, Young Adult, Enzyme Replacement Therapy adverse effects, Fabry Disease drug therapy
- Abstract
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension.
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- 2017
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38. Favourable effect of early versus late start of enzyme replacement therapy on plasma globotriaosylsphingosine levels in men with classical Fabry disease.
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Arends M, Wijburg FA, Wanner C, Vaz FM, van Kuilenburg ABP, Hughes DA, Biegstraaten M, Mehta A, Hollak CEM, and Langeveld M
- Subjects
- Adolescent, Adult, Age Factors, Aged, Antibodies blood, Child, Cohort Studies, Europe, Fabry Disease blood, Glycolipids immunology, Humans, Male, Middle Aged, Retrospective Studies, Sphingolipids immunology, Tandem Mass Spectrometry, Treatment Outcome, Young Adult, Enzyme Replacement Therapy methods, Fabry Disease drug therapy, Glycolipids blood, Sphingolipids blood
- Abstract
Background: The level of plasma globotriaosylsphingosine (lysoGb3) is an indication of disease severity in Fabry disease (FD) and its decrease during enzyme replacement therapy could be a reflection of treatment efficacy. Early treatment of FD may improve clinical outcome, but data to support this hypothesis are scarce. In this study we compared lysoGb3 decrease after ERT initiation in men with classical FD who started ERT before the age of 25 (early-treatment) with those who started later in life (late-treatment)., Methods: Treatment naïve men with classical FD from three centers of excellence in Europe were included. Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an inhibitory assay were performed in a single laboratory. Results were adjusted for lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT dose., Results: 85 patients were included, 21 in the early-treatment and 64 in the late-treatment group. LysoGb3 level at baseline was not different between the two groups (112 vs 114nmol/L, p=0.92). The adjusted odds ratio for reaching a lysoGb3 level<20nmol/L was 7.38 for the early-treatment versus late-treatment group (95% CI: 1.91-34.04, p=0.006). The adjusted lysoGb3 levels one year after ERT initiation was 12.9nmol/L lower in the early-treatment (95% CI: -20.1--5.8, p<0.001) compared to the late-treatment group., Conclusion: The current retrospective cohort study shows that initiation of ERT at younger age in men with classical Fabry disease results in a better biochemical response., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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39. Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study.
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Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, Elliott PM, Linthorst GE, Wijburg FA, Biegstraaten M, and Hollak CE
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- Adolescent, Adult, Child, Child, Preschool, Fabry Disease genetics, Female, Humans, Male, Middle Aged, Phenotype, Retrospective Studies, Survival Rate, Fabry Disease classification, Fabry Disease mortality
- Abstract
Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P <0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; P <0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype ( P <0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients., (Copyright © 2017 by the American Society of Nephrology.)
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- 2017
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40. Discontinuation of enzyme replacement therapy in Fabry disease in the Dutch cohort.
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Arends M, Linthorst GE, Hollak CE, and Biegstraaten M
- Subjects
- Adult, Disease Progression, Enzyme Replacement Therapy, Fabry Disease pathology, Female, Humans, Male, Middle Aged, Netherlands, Retrospective Studies, Treatment Failure, Treatment Refusal, Withholding Treatment, Fabry Disease drug therapy
- Abstract
Fabry disease (FD) is a progressive, multi-organ, lysosomal storage disease. Enzyme replacement therapy (ERT) is available for the treatment of the disease. While the reasons to initiate ERT have been frequently discussed, discontinuation of ERT is rarely reported. In this paper we describe our experiences with stopping ERT in FD. From 1999 through 2015, twenty-one patients discontinued ERT. These patients were generally older and more severely affected in comparison those who continued ERT. The reason to discontinue ERT switched from death or terminal illness in the first years towards treatment failure in more recent years. Three cases are described in more detail. We conclude that discontinuation of ERT should or may be considered in subgroups of FD patients although further studies on the effectiveness of ERT in subgroups of patients and the course of the disease after discontinuation of ERT are needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2016
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41. Position statement on the role of healthcare professionals, patient organizations and industry in European Reference Networks.
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Hollak CE, Biegstraaten M, Baumgartner MR, Belmatoug N, Bembi B, Bosch A, Brouwers M, Dekker H, Dobbelaere D, Engelen M, Groenendijk MC, Lachmann R, Langendonk JG, Langeveld M, Linthorst G, Morava E, Poll-The BT, Rahman S, Rubio-Gozalbo ME, Spiekerkoetter U, Treacy E, Wanders R, Zschocke J, and Hagendijk R
- Subjects
- Europe, Humans, Community Networks, Health Personnel standards, Patient Advocacy standards, Rare Diseases
- Abstract
A call from the EU for the set-up of European Reference Networks (ERNs) is expected to be launched in the first quarter of 2016. ERNs are intended to improve the care for patients with low prevalent or rare diseases throughout the EU by, among other things, facilitating the pooling and exchange of experience and knowledge and the development of protocols and guidelines. In the past, for example where costly orphan drugs have been concerned, industry has played an important role in facilitating consensus meetings and publication of guidelines. The ERNs should provide a unique opportunity for healthcare professionals and patients to lead these activities in an independent way. However, currently costs for networking activities are not to be covered by EU funds and alternative sources of funding are being explored. There is growing concern that any involvement of the industry in the funding of ERNs and their core activities may create a risk of undue influence. To date, the European Commission has not been explicit in how industry will be engaged in ERNs. We believe that public funding and a conflict of interest policy are needed at the level of the ERNs, Centers of Expertise (CEs), healthcare professionals and patient organizations with the aim of maintaining scientific integrity and independence. Specific attention is needed where it concerns the development of clinical practice guidelines. A proposal for a conflict of interest policy is presented, which may support the development of a framework to facilitate collaboration, safeguard professional integrity and to establish and maintain public acceptability and trust among patients, their organizations and the general public.
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- 2016
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42. In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease.
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van der Tol L, Verhamme C, van Schaik IN, van der Kooi AJ, Hollak CE, and Biegstraaten M
- Abstract
Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an α-galactosidase A enzyme deficiency due to pathogenic variants in the α-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling., Objectives: We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis., Methods: All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of ≥1 abnormal QST modality and an abnormal IENFD., Results: Twenty-six patients participated (nonclassical FD n = 18, 9 males; no FD n = 5, 3 males; uncertain n = 3, 1 male). Of the patients classified as nonclassical FD, 28% had ≥1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had ≥1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%., Conclusions: In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD.
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- 2016
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43. Cornea verticillata supports a diagnosis of Fabry disease in non-classical phenotypes: results from the Dutch cohort and a systematic review.
- Author
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van der Tol L, Sminia ML, Hollak CE, and Biegstraaten M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Corneal Diseases genetics, Fabry Disease genetics, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Netherlands, Phenotype, Prevalence, alpha-Galactosidase genetics, Corneal Diseases diagnosis, Fabry Disease diagnosis
- Abstract
Background: Screening for Fabry disease (FD) increasingly reveals individuals without characteristic features and with a variant of unknown significance in the α-galactosidase A (GLA) gene. Cornea verticillata (CV) assessment, as a characteristic sign of FD, may be a valuable diagnostic tool to assess whether these individuals have a non-classical phenotype or no FD at all., Methods: We performed a systematic review to estimate the prevalence of CV in FD. Additionally, CV prevalence was assessed in the Dutch FD cohort. Data were stratified by gender and phenotype (classical, non-classical, uncertain, no-FD) using predefined criteria., Results: CV was assessed in 21 cohorts (n=753, 330 men, age 0-85 years). Pooled prevalence was 69% (74% men, 66% women). In six studies, 77 (19 men) individuals with a non-classical or uncertain diagnosis were identified. Individual data were available in 4/6 studies (n=66, 16 men). CV was present in 24% (n=16, 2 men). 101 (35 men) subjects from the Dutch cohort were grouped as classical, of whom 86% (94% men, 82% women including five women who used amiodarone) had CV. Of the 25 (11 men) non-classical patients, 4 (three men) had CV. Subjects in the uncertain and no-FD groups did not have CV., Conclusions: CV is related to classical or biopsy-proven non-classical FD, with a very high sensitivity in classical men. Thus, presence of CV in an individual with an uncertain diagnosis of FD indicates a pathogenic GLA variant, in the absence of medication that may induce CV; if CV is absent, FD cannot be excluded., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
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44. Post-authorisation assessment of orphan drugs.
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Hollak CEM, Biegstraaten M, Levi M, and Hagendijk R
- Subjects
- European Union, Fabry Disease drug therapy, Humans, Rare Diseases drug therapy, Drug Approval organization & administration, Orphan Drug Production
- Published
- 2015
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45. Quality of life in patients with Fabry disease: a systematic review of the literature.
- Author
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Arends M, Hollak CE, and Biegstraaten M
- Subjects
- Enzyme Replacement Therapy, Fabry Disease physiopathology, Female, Humans, Male, Quality of Life, Surveys and Questionnaires, Fabry Disease pathology
- Abstract
Fabry disease (FD), caused by deficiency of the lysosomal enzyme α-galactosidase-A, is a progressive multisystem disease. The disease is X-linked with generally more severe manifestations in males, but can impact on quality of life (QoL) of both male and female patients. The purpose of this literature review is to analyse the currently available data concerning QoL measurement, specifically which questionnaires have been used to measure QoL, how patients with FD score compared to the general population, and the effects of enzyme replacement therapy (ERT) on QoL. Fifty-four articles were relevant for this literature review. Patients with FD had a lower QoL compared to the general population. No definite conclusions could be drawn from the studies on the effect of ERT on QoL; natural history data is scarce, changes observed were limited and the cohorts were of small size. We propose that a FD specific questionnaire be made to accurately assess QoL in patients with FD.
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- 2015
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46. Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease.
- Author
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Smid BE, van der Tol L, Biegstraaten M, Linthorst GE, Hollak CE, and Poorthuis BJ
- Subjects
- Adolescent, Adult, Aged, Fabry Disease genetics, Female, Humans, Male, Middle Aged, Phenotype, Trihexosylceramides blood, Young Adult, alpha-Galactosidase blood, Fabry Disease blood, Glycolipids blood, Sphingolipids blood
- Abstract
Background: Fabry disease (FD), a lysosomal storage disorder caused by α-galactosidase A (GLA) gene variants, has a heterogeneous phenotype. GLA variants can lead to classical FD, an attenuated non-classical phenotype, or no disease at all. This study investigates the value of plasma globotriaosylsphingosine (lysoGb3) to distinguish between these groups. This is of particular importance in the diagnosis of individuals with a GLA variant and an uncertain diagnosis of FD, lacking characteristic features of classical FD., Methods: Subjects with GLA variants were grouped as classical, non-classical, uncertain or no FD, using strict phenotypical, biochemical and histological criteria. Plasma lysoGb3 was assessed by LC/MS/MS (normal ≤ 0.6 nmol/L)., Results: 154 subjects were grouped into classical (38 males (M), 66 females (F)), non-classical (13 M, 14 F), uncertain (5M, 9 F) or no FD (6M, 3F). All subjects with a classical phenotype had elevated lysoGb3 values (M: range 45-150, F: 1.5-41.5). LysoGb3 values in patients with a non-classical phenotype (M: 1.3-35.7, F: 0.5-2.0) were different from healthy controls (M: p<0.01, F: p<0.05), but females overlapped with controls. In the no-FD group, lysoGb3 was normal., Conclusions: LysoGb3 is a reliable diagnostic tool to discern classical FD from subjects without FD. This study suggests that the same applies to patients with a non-classical phenotype. LysoGb3 values of female patients overlap with controls. Consequently, in uncertain cases, increased lysoGb3 values are very suggestive for FD, but normal values cannot exclude FD. Confirmation in larger cohorts and data on the specificity of small lysoGb3 increases are necessary., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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47. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.
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Biegstraaten M, Arngrímsson R, Barbey F, Boks L, Cecchi F, Deegan PB, Feldt-Rasmussen U, Geberhiwot T, Germain DP, Hendriksz C, Hughes DA, Kantola I, Karabul N, Lavery C, Linthorst GE, Mehta A, van de Mheen E, Oliveira JP, Parini R, Ramaswami U, Rudnicki M, Serra A, Sommer C, Sunder-Plassmann G, Svarstad E, Sweeb A, Terryn W, Tylki-Szymanska A, Tøndel C, Vujkovac B, Weidemann F, Wijburg FA, Woolfson P, and Hollak CE
- Subjects
- Adolescent, Disease Progression, Fabry Disease pathology, Female, Humans, Isoenzymes administration & dosage, Male, Practice Guidelines as Topic, alpha-Galactosidase administration & dosage, Enzyme Replacement Therapy, Fabry Disease drug therapy, Isoenzymes therapeutic use, alpha-Galactosidase therapeutic use
- Abstract
Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD., Methods: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement., Results: For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m(2)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped., Conclusion: The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.
- Published
- 2015
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48. Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy.
- Author
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Suntjens EB, Smid BE, Biegstraaten M, Dreschler WA, Hollak CE, and Linthorst GE
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Audiometry, Pure-Tone, Auditory Threshold, Cross-Sectional Studies, Disease Progression, Fabry Disease complications, Fabry Disease diagnosis, Fabry Disease enzymology, Fabry Disease genetics, Female, Hearing Loss, Bilateral diagnosis, Hearing Loss, Bilateral psychology, Hearing Loss, Sensorineural diagnosis, Hearing Loss, Sensorineural psychology, Humans, Longitudinal Studies, Male, Middle Aged, Netherlands, Retrospective Studies, Risk Factors, Severity of Illness Index, Sex Factors, Treatment Outcome, Young Adult, alpha-Galactosidase genetics, Enzyme Replacement Therapy, Fabry Disease drug therapy, Hearing Loss, Bilateral etiology, Hearing Loss, Sensorineural etiology, alpha-Galactosidase therapeutic use
- Abstract
Introduction: Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce., Methods: This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups: classical and non-classical FD patients with or without ERT. To study effects of ERT, longitudinal data, corrected for age and gender according to ISO-1999 guidelines, were analyzed with mixed models., Results: In the cross-sectional analysis, 107 FD patients (41 males), median age 47.6 years (18.8-80.6) were analyzed. At baseline, i.e., before start of ERT, HL was present in 18 patients (16.8 %), of whom four had bilateral sensorineural HL. HL was more often present in patients with the classical phenotype than non-classical patients (p < 0.01). Likewise, males had more often HL than females. Compared to the general population, FD patients show a median HL of 8.2 dB at low frequencies (p < 0.01) and 29.5 dB at ultra-high frequencies (p < 0.01). Longitudinal analyses (n = 91) revealed that ERT treated patients show a similar rate of decline, not significantly different from healthy controls., Conclusion: Adult FD patients, especially classical affected males, show impaired hearing. Longitudinal analyses during ERT in these patients demonstrates a decline of HL similar to healthy controls, but HL present before initiation of therapy cannot be reversed. Whether early therapy can prevent hearing loss is unknown.
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- 2015
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49. Chronic kidney disease and an uncertain diagnosis of Fabry disease: approach to a correct diagnosis.
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van der Tol L, Svarstad E, Ortiz A, Tøndel C, Oliveira JP, Vogt L, Waldek S, Hughes DA, Lachmann RH, Terryn W, Hollak CE, Florquin S, van den Bergh Weerman MA, Wanner C, West ML, Biegstraaten M, and Linthorst GE
- Subjects
- Adult, Algorithms, Biopsy, Delphi Technique, Female, Genetic Variation, Humans, Male, alpha-Galactosidase genetics, Fabry Disease diagnosis, Renal Insufficiency, Chronic diagnosis
- Abstract
Background and Objectives: Screening for Fabry disease (FD), an X-linked lysosomal storage disorder, reveals a significant number of individuals with a genetic variant of unknown significance without classical FD manifestations; these variants in the α-galactosidase A gene often result in a high residual leukocyte α-galactosidase A and it is unclear whether these individuals suffer from FD. Therefore, a structured diagnostic approach is warranted. We present a diagnostic algorithm on how to approach adults with chronic kidney disease and an uncertain diagnosis of FD nephropathy., Design, Setting, Participants, and Measurements: A modified Delphi procedure was conducted to reach consensus among 11 FD experts. A systematic review was performed to identify possible criteria that could confirm or exclude FD nephropathy., Results: The gold standard for FD nephropathy was defined as characteristic storage on electron microscopy (EM) in a kidney biopsy in the absence of medication that may induce similar storage. The suggested criteria to confirm FD nephropathy are as follows: 'renal cysts', 'Maltese cross sign', 'immunohistochemical staining of Gb3 in urine' and 'high urinary Gb3'; and to exclude FD nephropathy: 'absence of renal cysts', 'small kidneys' and 'high protein excretion' were rejected because of low or uncertain specificity. Urinary Gb3 may be increased in other kidney diseases and there was no agreement on this criterion, although a third of the panel indicated that it is sufficient to diagnose FD nephropathy. The 'Maltese cross sign' and 'high urinary Gb3' were selected as red flags to suggest the possibility of FD nephropathy, but are not sufficient for a definite diagnosis of FD nephropathy., Conclusions: In adults with chronic kidney disease, an α-galactosidase A gene variant and an uncertain diagnosis of FD, a kidney biopsy with EM analysis should be performed to confirm or reject the diagnosis of FD nephropathy. Other criteria currently cannot substitute for a biopsy in these cases., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
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50. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications.
- Author
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van Dussen L, Biegstraaten M, Dijkgraaf MG, and Hollak CE
- Subjects
- Adult, Disease Progression, Gaucher Disease complications, Gaucher Disease physiopathology, Humans, Netherlands, Splenectomy, Bone Diseases complications, Enzyme Replacement Therapy, Gaucher Disease therapy
- Abstract
Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.
- Published
- 2014
- Full Text
- View/download PDF
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