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EFFICACY AND SAFETY OF ENZYME REPLACEMENT THERAPY IN CHILDREN WITH MUCOPOLYSACCHARIDOSIS TYPE I, II, AND VI: A SINGLE-CENTER COHORT STUDY

https://doi.org/10.15690/vsp.v17i1.1858

Abstract

Background. There are limited data on the efficacy of long-term enzyme replacement therapy (ERT) in children with mucopolysaccharidosis (MPS).

Objective. Our aim was to study the efficacy and safety of long-term ERT in children with MPS type I, II, and VI.

Methods. We analyzed the results of ERT with laronidase, idursulfase, and galsulfase in children with MPS type I, II, and VI admitted to the federal research center from January 2007 to November 2016. The response rate was assessed by the level of normalized urinary excretion of glycosaminoglycans (GAGs) (the ratio of GAGs concentration to urine creatinine) recalculated in percent (%) exceedance of the upper limit of normal for the corresponding age. Data on the administered therapy and its results, including adverse events, is extracted from the medical records of in-patients.

Results. The results of treatment (intravenous infusions, intervals between administrations from 4 to 10 days) were studied in 33 children (5 of them were girls) with MPS type I (n = 4; laronidase at a dose of 0.58 mg/kg), II (n = 26; idursulfase at a dose of 0.5 mg/kg), and VI (n = 3; galsulfase at a dose of 1 mg/kg). A decrease in the normalized urinary excretion of GAGs from 376% (172; 791) to 54% (0; 146) exceedance of the upper limit of normal for the age (p < 0.001) was noted in the course of ERT lasting (median) 27 (14; 41) months. A decrease in the normalized GAGs excretion below the upper limit of normal for the age was established in 12/33 (36%) patients. ERT-associated adverse events were identified in 12 patients; one case required a two-fold therapy interruption. The development of nephrotic syndrome in the course of ERT in patients with severe MPS II was first described.

Conclusion. Long-term ERT in children with MPS type I, II, and VI is characterized by acceptable efficacy and safety. Key words: children, mucopolysaccharidosis, enzyme replacement therapy, laronidase, idursulfase, galsulfase, glycosaminoglycans.

About the Authors

Liliia A. Osipova
National Medical Research Center of Children’s Health
Russian Federation
Moscow
Disclosure of interest:

Not declared



Ludmila M. Kuzenkova
National Medical Research Center of Children’s Health; Sechenov First Moscow State Medical University
Russian Federation
Moscow


Leyla S. Namazova-Baranova
National Medical Research Center of Children’s Health
Russian Federation
Moscow
Disclosure of interest:

Conflict of interests is available at http://pf.spr-journal.ru/jour/manager/files/ НамазоваКонфинт.pdf



Anait K. Gevorkyan
National Medical Research Center of Children’s Health
Russian Federation
Moscow


Tatiana V. Podkletnova
National Medical Research Center of Children’s Health
Russian Federation
Moscow


Nikolay A. Mayanskiy
National Medical Research Center of Children’s Health
Russian Federation
Moscow
Disclosure of interest:

Receiving research grants as well as speaker fees from pharmaceutical companies Pfizer and GlaxoSmithKline. Ludmila M. Kuzenkova, Anait K. Gevorkyan, Tatiana V. Podkletnova, Nato D. Vashakmadze give lectures for Sanofi Genzyme, Shayer, and BioMarin



Grigoriy V. Revunenkov
National Medical Research Center of Children’s Health
Russian Federation
Moscow


Nato D. Vashakmadze
National Medical Research Center of Children’s Health; Pirogov Russian National Research Medical University
Russian Federation
Moscow


References

1. Braunlin EA. Cardiac involvement in the mucopolysaccharide disoders. In: Moller JH, Hoffman JI, editors. Pediatric cardiovascular medicine. 2nd ed. NY: Wiley-Blackwell; 2012. pp. 982–991.

2. Neufeld E, Muenzer J. The mucopolysaccharidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. NY: McGraw-Hill; 2001. pp. 3421–3452.

3. Valayannopoulos V, Nicely H, Harmatz P, Turbeville S. Mucop olysaccharidosis VI. Orphanet J Rare Dis. 2010;5:5. doi: 10.1186/1750-1172-5-5.

4. Giugliani R, Federhen A, Rojas MV, et al. Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment. Genet Mol Biol. 2010;33(4):589–604. doi: 10.1590/S1415-4757201000 5000093.

5. Tomatsu S, Yasuda E, Patel P, et al. Morquio A syndrome: diagnosis and current and future therapies. Pediatr Endocrinol Rev Per. 2014;12 Suppl 1:141–151.

6. Gosudarstvennyi reestr lekarstvennykh sredstv. (In Russ). Доступно по: http://www.grls.rosminzdrav.ru/grls.aspx. Ссылка активна на 10.02.2018.

7. Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001;344(3): 182–188. doi: 10.1056/Nejm200101183440304.

8. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, et al. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007; 90(3):329-337. doi: 10.1016/j.ymgme.2006.09.001.

9. Harmatz P, Kramer W, Hopwood J, et al. Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux–Lamy syndrome): a phase I/II study. Acta Paediatr. 2005;94(0):61–68. doi: 10.1080/08035320510028139.

10. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, doubleblinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (Laronidase). J Pediatr. 2004;144(5): 581–588. doi: 10.1016/j.jpeds.2004.01.046.

11. Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006;8(8): 465–473. doi: 10.1097/01.gim.0000232477.37660.fb.

12. Harmatz P, Ketteridge D, Giugliani R, et al. Direct comparison of measures of endurance, mobility, and joint function during enzymereplacement therapy of mucopolysaccharidosis VI (MaroteauxLamy syndrome): Results after 48 weeks in a phase 2 openlabel clinical study of recombinant human N-acetylgalactosamine 4-sulfatase. Pediatrics. 2005;115(6):e681–e689. doi: 10.1542/peds.2004-1023.

13. Clarke LA, Wraith JE, Beck M, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009;123(1):229–240. doi: 10.1542/peds.2007-3847.

14. Muenzer J, Beck M, Eng CM, et al. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Genet Med. 2011;13(2):95–101. doi: 10.1097/GIM.0b013e3181fea459.

15. Harmatz P, Giugliani R, Schwariz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a Phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006;148(4):533–539. doi: 10.1016/j.jpeds. 2005.12.014.

16. Elaprase (idursulfase) solution for intravenous infusion. Cambridge: Shire Human Genetic Therapies; 2011.

17. Mehta A, Winchester B. Lysosomal Storage Disease: A Practical Guide. NY: Wiley-Blackwell; 2012.

18. Mayansky NA, Blinova TA, Podkletnova TV, et al. Quantative determination of urinary glycosaminoglycans in reference individuals and patients with mucopolysaccharidoses by the dimethylmethylene blue assay. Pediatric diagnostics. 2013;5(1):21–26. (In Russ).

19. Detskaya ul’trazvukovaya diagnostika. Ed by M.I. Pykov, K.V. Vatolin. Mоscow: Izdatel’skii dom Vidar-M; 2001. (In Russ).

20. Ul’trazvukovaya diagnostika v neonatologii i pediatrii: differentsial’no-diagnosticheskie kriterii. Prakticheskoe rukovodstvo. Ed by I.V. Dvoryakovskii, G.M. Dvoryakovskaya. Moscow: Atmosfera; 2012. 172 p. (In Russ).

21. Rybakova MK, Alekhin MN, Mit’kov VV. Prakt icheskoe rukovodstvo po ul’trazvukovoi diagnostike. Ekhokardiografiya. Moscow: Vidar-M; 2008. (In Russ).

22. Pano A, Barbier AJ, Bielefeld B, et al. Immunogenicity of idursulfase and clinical outcomes in very young patients (16 months to 7.5 years) with mucopolysaccharidosis II (Hunter syndrome). Orphanet J Rare Dis. 2015;10(1):50. doi: 10.1186/s13023-015-0265-2.

23. Parini R, Rigoldi M, Tedesco L, et al. Enzymatic replacement therapy for Hunter disease: up to 9 years experience with 17 patients. Mol Genet Metab Rep. 2015;3:65–74. doi: 10.1016/j.ymgmr.2015.03.011.

24. Lampe C, Bosserhoff AK, Burton BK, et al. Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: an international case series. J Inherit Metab Dis. 2014;37(5):823–829. doi: 10.1007/s10545-014-9686-7.

25. Giugliani R, Hwu WL, Tylki-Szymanska A, et al. A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4–7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy. Genet Med. 2014;16(6):435–441. doi: 10.1038/gim.2013.162.

26. Kilic M, Dursun A, Coskun T, et al. Genotypic-phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey. Am J Med Genet A. 2017;173(11):2954–2967. doi: 10.1002/ajmg.a.38459.

27. Dvoryakovskaya GM, Zhurkova NV, Sil’nova IV, et al. Ultrasound assessment of internal organs in children with mucopolysaccharidosis. Ultrasound & functional diagnostics. 2010; (3):34–42. (In Russ).

28. Krawiec P, Pac-Kozuchowska E, Melges B, et al. From hypertransaminasemia to mucopolysaccharidosis IIIA. Ital J Pediatr. 2014;40:97. doi: 10.1186/s13052-014-0097-z.

29. Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008;167(3):267–277. doi: 10.1007/s00431-007-0635-4.

30. Sifuentes M, Doroshow R, Hoft R, et al. A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab. 2007;90(2):171–180. doi: 10.1016/j.ymgme.2006.08.007.

31. Muenzer J, Beck M, Giugliani R, et al. Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. Genet Med. 2011;13(2):102–109. doi: 10.1097/GIM.0b013e318206786f.

32. Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (Laronidase). Pediatrics. 2007;120(1): e37–e46. doi: 10.1542/peds.2006-2156.

33. Tomanin R, Zanetti A, D’Avanzo F, et al. Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 years. Orphanet J Rare Dis. 2014;9(1). doi: 10.1186/s13023-014-0129-1.

34. Brands MM, Frohn-Mulder IM, Hagemans ML, et al. Muco po lysaccharidosis: Cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI. J Inherit Metab Dis. 2013;36(2):227–234. doi: 10.1007/s10545-011-9444-z.

35. Hunley TE, Corzo D, Dudek M, et al. Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease. Pediatrics. 2004;114(4):e532–e535. doi: 10.1542/peds.2003-0988-L.

36. asn-online.org [Internet]. Lathara Z, Ambruzs JM, Cohen EP. Alloimmune membranous nephropathy in Fabry Disease. Kidney Week 2015. Abstract Supplement [cited 2017 Oct 12]. Available from: https://www.asn-online.org/education/kidneyweek/archives/.

37. Debiec H, Valayannopoulos V, Boyer O, et al. Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy. J Am Soc Nephrol. 2014;25(4):675–680. doi: 10.1681/Asn.2013030290.

38. Lin HY, Chuang CK, Chen MR, et al. Cardiac structure and function and effects of enzyme replacement therapy in patients with mucopolysaccharidoses I, II, IVA, and VI. Mol Genet Metab. 2016;117(4):431–437. doi: 10.1016/j.ymgme.2016.02.003.

39. Braunlin EA, Berry JM, Whitley CB. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am J Cardiol. 2006;98(3):416–418. doi: 10.1016/j.amjcard.2006.02.047.

40. Braunlin E, Rosenfeld H, Kampmann C, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme (R)) therapy. J Inherit Metab Dis. 2013;36(2):385–394. doi: 10.1007/s10545-012-9481-2.


Review

For citations:


Osipova L.A., Kuzenkova L.M., Namazova-Baranova L.S., Gevorkyan A.K., Podkletnova T.V., Mayanskiy N.A., Revunenkov G.V., Vashakmadze N.D. EFFICACY AND SAFETY OF ENZYME REPLACEMENT THERAPY IN CHILDREN WITH MUCOPOLYSACCHARIDOSIS TYPE I, II, AND VI: A SINGLE-CENTER COHORT STUDY. Current Pediatrics. 2018;17(1):76-84. https://doi.org/10.15690/vsp.v17i1.1858

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