Terapia de reemplazo enzimático en la Enfermedad de Fabry: la dosis es importante
Resumen
La enfermedad de Fabry es una enfermedad rara ligada al X consecuencia de la deficiencia de α-galactosidasa A lisosomal, lo que genera un depósito excesivo de glicoesfingolípidos, predominantemente globotriaosilceramida (Gl3) y mortalidad de causa renal cardíaca y neurológica. El tratamiento actual consiste en la terapia de reemplazo enzimático, lo que intenta reemplazar por vía intravenosa la enzima deficiente. Existen en el mercado europeo y latinoamericano dos formulaciones de agalsidasa: agalsidasa alfa y agalsidasa beta, lo que permite al médico elegir el tratamiento. Sin embargo, la Food and Drug Administration en Estados Unidos rechazó aprobar la agalsidasa alfa. La diferencia fundamental entre agalsidasa alfa y agalsidasa beta es la dosis autorizada: 0,2 mg/kg y 1 mg/kg cada dos semanas respectivamente. Durante años esta diferencia tan grande de dosis sorprendió a los clínicos. Sin embargo varios estudios recientes sugieren que hay un efecto dosis-respuesta y que para algunos pacientes la dosis de 0,2 mg/kg cada dos semanas puede ser insuficiente. Sin embargo, no existen herramientas que permitan predecir que pacientes van a necesitar una dosis más alta para detener o enlentecer la progresión de la enfermedad. En esta revisión resumimos el estado actual del conocimiento sobre el impacto Tratamiento en la enfermedad de Fabry de las diferentes dosis y su eficacia en tratamiento de la enfermedad de Fabry.
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Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.
Desnick RJ, Ioannou YA, Eng CM. Galactosidase a deficiency: Fabry disease. En: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic bases of inherited disease. 8th ed. New York: MacGraw-Hill; 2001. p. 3733-74.
Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al. Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry’s disease. N Engl J Med. 2001;345(1):9-16.
Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001;285(21):2743-9.
Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry’s disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967;276(21):1163-7.
Desnick RJ, Simmons RL, Allen KY, Woods JE, Anderson CF, Najarian JS, et al. Correction of enzymatic deficiencies by renal transplantation: Fabry’s disease. Surgery. 1972;72(2):203-11.
Desnick RJ. Enzyme replacement therapy for Fabry disease: lessons from two alpha-galactosidase A orphan products and one FDA approval. Expert Opin Biol Ther. 2004;4(7):1167-76.
Schiffmann R, Hauer P, Freeman B, Ries M, Scott LJ, Polydefkis M, et al. Enzyme replacement therapy and intraepidermal innervation density in Fabry disease. Muscle Nerve. 2006;34(1):53-6.
Furujo M, Kubo T, Kobayashi M, Ohashi T. Enzyme replacement therapy in two Japanese siblings with Fabry disease, and its effectiveness on angiokeratoma and neuropathic pain. Mol Genet Metab. 2013;110(3):405-10.
Hughes DA, Deegan PB, Milligan A, Wright N, Butler LH, Jacobs A, et al. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease. Mol Genet Metab. 2013;109(3):269-75.
Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M. Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology. 2004;62(7):1066-72.
Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004;75(1):65-74.
Weidemann F, Krämer J, Duning T, Lenders M, Canaan-Kühl S, Krebs A, et al. Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch. J Am Soc Nephrol. 2014;25(4):837-49.
Lenders M, Canaan-Kühl S, Krämer J, Duning T, Reiermann S, Sommer C, et al. Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up. J Am Soc Nephrol. 2016;27(3):952-62.
Politei J, Schenone AB, Cabrera G, Heguilen R, Szlago M. Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations - different outcome? Clin Genet. 2016;89(1):88-92.
Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007;146(2):77-86.
Estados Unidos. Center for Drug Evaluation and Research. Food and Drug Administration Endocrinologic and Metabolic Advisory Committee Meetting (2003, January 14). Disponible en: http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3917T2.htm [Acceso: 10-11-2015].
Tøndel C, Bostad L, Larsen KK, Hirth A, Vikse BE, Houge G, et al. Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol. 2013;24(1):137-48.
Fervenza FC, Torra R, Warnock DG. Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease. Biologics. 2008;2(4):823-43.
Torra R, Algaba F, Ars E, Santin S, Fernández-Llama P, Ballarin J. Preservation of renal function in a patient with Fabry nephropathy on enzyme replacement therapy. Clin Nephrol. 2008;69(6):445-9.
Schiffmann R, Askari H, Timmons M, Robinson C, Benko W, Brady RO, et al. Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol. 2007;18(5):1576-83.
Schiffmann R, Swift C, Wang X, Blankenship D, Ries M. A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease. J Inherit Metab Dis. 2015;38(6):1129-36.
Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, et al. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation. 2003;108(11):1299-301.
Weidemann F, Sanchez-Niño MD, Politei J, Oliveira JP, Wanner C, Warnock DG, et al. Fibrosis: a key feature of Fabry disease with potential therapeutic implications. Orphanet J Rare Dis. 2013;8:116.
Weidemann F, Niemann M, Breunig F, Herrmann S, Beer M, Störk S, et al. Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation. 2009;119(4):524-9.
Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, et al. Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry. Genet Med. 2013;15(12):958-65.
Hughes DA, Elliott PM, Shah J, Zuckerman J, Coghlan G, Brookes J, et al. Effects of enzyme replace ment therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart. 2008;94(2):153-8.
Kampmann C, Linhart A, Devereux RB, Schiffmann R. Effect of agalsidase alfa replacement therapy on Fabry disease-related hypertrophic cardiomyopathy: a 12- to 36-month, retrospective, blinded echocardiographic pooled analysis. Clin Ther. 2009; 31(9):1966-76.
Romero Trejo J. Ventricular tachyarrhythmias in Fabry disease: relevance of enzyme replacement therapy dose apropos of a case [resumen]. Latam Fabry Round Table (3° : Cancún, México : 2015 april 16-18]. Disponible en: http://issuu.com/lapaproducoes/docs/abstract_em_10.04 [consulta: 21-11-2015].
Fellgiebel A, Gartenschläger M, Wildberger K, Scheurich A, Desnick RJ, Sims K. Enzyme replacement therapy stabilized white matter lesion progression in Fabry disease. Cerebrovasc Dis. 2014;38(6):448-56.
Ferreira S, Auray-Blais C, Boutin M, Lavoie P, Nunes JP, Martins E, et al. Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma. Clin Chim Acta. 2015;447:96-104.
Schiffmann R, Murray GJ, Treco D, Daniel P, Sellos-Moura M, Myers M, et al. Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A. 2000;97(1):365-70.
Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, et al. A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet. 2001;68(3):711-22.
Sanchez-Niño MD, Sanz AB, Carrasco S, Saleem MA, Mathieson PW, Valdivielso JM, et al. Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol Dial Transplant. 2011;26(6):1797-802.
Smid BE, Rombach SM, Aerts JM, Kuiper S, Mirzaian M, Overkleeft HS, et al. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients. Orphanet J Rare Dis. 2011;6:69.
Goker-Alpan O, Nedd K, Shankar SP, Lien YH, Weinreb N, Wijatyk A, et al. Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa. JIMD Rep. 2015;23:7-15.
Warnock DG, ed. Biomarkers, Progression and Treatment Opportunities. Abstracts. Update on Fabry Nephropathy (4th : Manchester, UK : June 1-2, 2015). Nephron. 2015;130(2):77-91.
Sirrs SM, Bichet DG, Casey R, Clarke JT, Lemoine K, Doucette S, et al. Outcomes of patients treated through the Canadian Fabry disease initiative. Mol Genet Metab. 2014;111(4):499-506.
