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Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase).
J Pediatr. 2004 May; 144(5):581-8.JPed

Abstract

OBJECTIVE

To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I).

STUDY DESIGN

This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test.

RESULTS

The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects.

CONCLUSIONS

In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile.

Authors+Show Affiliations

Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom. ed.wraith@cmmc.nhs.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15126990

Citation

Wraith, James E., et al. "Enzyme Replacement Therapy for Mucopolysaccharidosis I: a Randomized, Double-blinded, Placebo-controlled, Multinational Study of Recombinant Human alpha-L-iduronidase (laronidase)." The Journal of Pediatrics, vol. 144, no. 5, 2004, pp. 581-8.
Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004;144(5):581-8.
Wraith, J. E., Clarke, L. A., Beck, M., Kolodny, E. H., Pastores, G. M., Muenzer, J., Rapoport, D. M., Berger, K. I., Swiedler, S. J., Kakkis, E. D., Braakman, T., Chadbourne, E., Walton-Bowen, K., & Cox, G. F. (2004). Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). The Journal of Pediatrics, 144(5), 581-8.
Wraith JE, et al. Enzyme Replacement Therapy for Mucopolysaccharidosis I: a Randomized, Double-blinded, Placebo-controlled, Multinational Study of Recombinant Human alpha-L-iduronidase (laronidase). J Pediatr. 2004;144(5):581-8. PubMed PMID: 15126990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). AU - Wraith,James E, AU - Clarke,Lorne A, AU - Beck,Michael, AU - Kolodny,Edwin H, AU - Pastores,Gregory M, AU - Muenzer,Joseph, AU - Rapoport,David M, AU - Berger,Kenneth I, AU - Swiedler,Stuart J, AU - Kakkis,Emil D, AU - Braakman,Tanja, AU - Chadbourne,Elenie, AU - Walton-Bowen,Karen, AU - Cox,Gerald F, PY - 2004/5/6/pubmed PY - 2004/6/4/medline PY - 2004/5/6/entrez SP - 581 EP - 8 JF - The Journal of pediatrics JO - J. Pediatr. VL - 144 IS - 5 N2 - OBJECTIVE: To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I). STUDY DESIGN: This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test. RESULTS: The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects. CONCLUSIONS: In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile. SN - 0022-3476 UR - https://www.unboundmedicine.com/medline/citation/15126990/Enzyme_replacement_therapy_for_mucopolysaccharidosis_I:_a_randomized_double_blinded_placebo_controlled_multinational_study_of_recombinant_human_alpha_L_iduronidase__laronidase__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3476(04)00091-5 DB - PRIME DP - Unbound Medicine ER -