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Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I.
Pediatrics. 2009 Jan; 123(1):229-40.Ped

Abstract

OBJECTIVE

Our goal was to evaluate the long-term safety and efficacy of recombinant human alpha-l-iduronidase (laronidase) in patients with mucopolysaccharidosis I.

PATIENTS AND METHODS

All 45 patients who completed a 26-week, double-blind, placebo-controlled trial of laronidase were enrolled in a 3.5-year open-label extension study. Mean patient age at baseline was 16 (range: 6-43) years. All patients had attenuated disease (84% Hurler-Scheie, 16% Scheie phenotypes). Clinical, biochemical, and health outcomes measures were evaluated through the extension phase. Changes are presented as the mean +/- SEM.

RESULTS

All 40 patients (89%) who completed the trial received at least 80% of scheduled infusions. As shown in earlier trials, urinary glycosaminoglycan levels decreased within the first 12 weeks and liver volume decreased within the first year. Percent predicted forced vital capacity remained stable, with a linear slope of -0.78 percentage points per year. The 6-minute walk distance increased 31.7 +/- 10.2 m in the first 2 years, with a final gain of 17.1 +/- 16.8 m. Improvements in the apnea/hypopnea index (decrease of 7.6 +/- 4.5 events per hour among the patients with significant baseline sleep apnea) and shoulder flexion (increase of 17.4 degrees +/- 3.6 degrees) were most rapid during the first 2 years. Improvements in the Child Health Assessment Questionnaire/Health Assessment Questionnaire disability index (decrease of 0.31 +/- 0.11, signifying a clinically meaningful improvement in activities of daily living) were gradual and sustained over the treatment period. Laronidase infusions were generally well tolerated except in 1 patient who experienced an anaphylactic reaction. Infusion-associated reactions, which occurred in 53% of the patients, were mostly mild, easily managed, and decreased markedly after 6 months. One patient died as a result of an upper respiratory infection unrelated to treatment. Antibodies to laronidase developed in 93% of the patients; 29% of the patients were seronegative at their last assessment.

CONCLUSIONS

This trial demonstrates the long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I and highlights the magnitude and chronology of treatment effects. Prompt diagnosis and early treatment will maximize treatment outcomes.

Authors+Show Affiliations

University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia, Canada. lclarke@cw.bc.caNo 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)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19117887

Citation

Clarke, Lorne A., et al. "Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I." Pediatrics, vol. 123, no. 1, 2009, pp. 229-40.
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):229-40.
Clarke, L. A., Wraith, J. E., Beck, M., Kolodny, E. H., Pastores, G. M., Muenzer, J., Rapoport, D. M., Berger, K. I., Sidman, M., Kakkis, E. D., & Cox, G. F. (2009). Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics, 123(1), 229-40. https://doi.org/10.1542/peds.2007-3847
Clarke LA, et al. Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I. Pediatrics. 2009;123(1):229-40. PubMed PMID: 19117887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. AU - Clarke,Lorne A, AU - Wraith,J Edmond, AU - Beck,Michael, AU - Kolodny,Edwin H, AU - Pastores,Gregory M, AU - Muenzer,Joseph, AU - Rapoport,David M, AU - Berger,Kenneth I, AU - Sidman,Marisa, AU - Kakkis,Emil D, AU - Cox,Gerald F, PY - 2009/1/2/entrez PY - 2009/1/2/pubmed PY - 2009/2/7/medline SP - 229 EP - 40 JF - Pediatrics JO - Pediatrics VL - 123 IS - 1 N2 - OBJECTIVE: Our goal was to evaluate the long-term safety and efficacy of recombinant human alpha-l-iduronidase (laronidase) in patients with mucopolysaccharidosis I. PATIENTS AND METHODS: All 45 patients who completed a 26-week, double-blind, placebo-controlled trial of laronidase were enrolled in a 3.5-year open-label extension study. Mean patient age at baseline was 16 (range: 6-43) years. All patients had attenuated disease (84% Hurler-Scheie, 16% Scheie phenotypes). Clinical, biochemical, and health outcomes measures were evaluated through the extension phase. Changes are presented as the mean +/- SEM. RESULTS: All 40 patients (89%) who completed the trial received at least 80% of scheduled infusions. As shown in earlier trials, urinary glycosaminoglycan levels decreased within the first 12 weeks and liver volume decreased within the first year. Percent predicted forced vital capacity remained stable, with a linear slope of -0.78 percentage points per year. The 6-minute walk distance increased 31.7 +/- 10.2 m in the first 2 years, with a final gain of 17.1 +/- 16.8 m. Improvements in the apnea/hypopnea index (decrease of 7.6 +/- 4.5 events per hour among the patients with significant baseline sleep apnea) and shoulder flexion (increase of 17.4 degrees +/- 3.6 degrees) were most rapid during the first 2 years. Improvements in the Child Health Assessment Questionnaire/Health Assessment Questionnaire disability index (decrease of 0.31 +/- 0.11, signifying a clinically meaningful improvement in activities of daily living) were gradual and sustained over the treatment period. Laronidase infusions were generally well tolerated except in 1 patient who experienced an anaphylactic reaction. Infusion-associated reactions, which occurred in 53% of the patients, were mostly mild, easily managed, and decreased markedly after 6 months. One patient died as a result of an upper respiratory infection unrelated to treatment. Antibodies to laronidase developed in 93% of the patients; 29% of the patients were seronegative at their last assessment. CONCLUSIONS: This trial demonstrates the long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I and highlights the magnitude and chronology of treatment effects. Prompt diagnosis and early treatment will maximize treatment outcomes. SN - 1098-4275 UR - https://www.unboundmedicine.com/medline/citation/19117887/Long_term_efficacy_and_safety_of_laronidase_in_the_treatment_of_mucopolysaccharidosis_I_ L2 - http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=19117887 DB - PRIME DP - Unbound Medicine ER -