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Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I.

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Title: Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I.
Authors: Clarke, Lorne A., Wraith, J. Edmond, Beck, Michael, Kolodny, Edwin H., Pastores, Gregory M., Muenzer, Joseph, Rapoport, David M., Berger, Kenneth I., Sidman, Marisa, Kakkis, Emil D., Cox, Gerald F.
Source: Pediatrics. Jan2009, Vol. 123 Issue 1, p229-240. 12p. 3 Charts, 7 Graphs.
Subjects: Mucopolysaccharidosis treatment, Placebos, Vital capacity (Respiration), Infusion therapy, Glycosaminoglycans, Apnea, Anaphylaxis, Respiratory infections, Immunoglobulins
Abstract: OBJECTIVE. Our goal was to evaluate the long-term safety and efficacy of recombinant human α-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I. PATIENTS AND METHODS. All 45 patients who completed a 26-week, double-blind, placebocontrolled 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° ± 3.6°) 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. [ABSTRACT FROM AUTHOR]
Copyright of Pediatrics is the property of American Academy of Pediatrics and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I.
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  Data: <searchLink fieldCode="AR" term="%22Clarke%2C+Lorne+A%2E%22">Clarke, Lorne A.</searchLink><br /><searchLink fieldCode="AR" term="%22Wraith%2C+J%2E+Edmond%22">Wraith, J. Edmond</searchLink><br /><searchLink fieldCode="AR" term="%22Beck%2C+Michael%22">Beck, Michael</searchLink><br /><searchLink fieldCode="AR" term="%22Kolodny%2C+Edwin+H%2E%22">Kolodny, Edwin H.</searchLink><br /><searchLink fieldCode="AR" term="%22Pastores%2C+Gregory+M%2E%22">Pastores, Gregory M.</searchLink><br /><searchLink fieldCode="AR" term="%22Muenzer%2C+Joseph%22">Muenzer, Joseph</searchLink><br /><searchLink fieldCode="AR" term="%22Rapoport%2C+David+M%2E%22">Rapoport, David M.</searchLink><br /><searchLink fieldCode="AR" term="%22Berger%2C+Kenneth+I%2E%22">Berger, Kenneth I.</searchLink><br /><searchLink fieldCode="AR" term="%22Sidman%2C+Marisa%22">Sidman, Marisa</searchLink><br /><searchLink fieldCode="AR" term="%22Kakkis%2C+Emil+D%2E%22">Kakkis, Emil D.</searchLink><br /><searchLink fieldCode="AR" term="%22Cox%2C+Gerald+F%2E%22">Cox, Gerald F.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Pediatrics%22">Pediatrics</searchLink>. Jan2009, Vol. 123 Issue 1, p229-240. 12p. 3 Charts, 7 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Mucopolysaccharidosis+treatment%22">Mucopolysaccharidosis treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Placebos%22">Placebos</searchLink><br /><searchLink fieldCode="DE" term="%22Vital+capacity+%28Respiration%29%22">Vital capacity (Respiration)</searchLink><br /><searchLink fieldCode="DE" term="%22Infusion+therapy%22">Infusion therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Glycosaminoglycans%22">Glycosaminoglycans</searchLink><br /><searchLink fieldCode="DE" term="%22Apnea%22">Apnea</searchLink><br /><searchLink fieldCode="DE" term="%22Anaphylaxis%22">Anaphylaxis</searchLink><br /><searchLink fieldCode="DE" term="%22Respiratory+infections%22">Respiratory infections</searchLink><br /><searchLink fieldCode="DE" term="%22Immunoglobulins%22">Immunoglobulins</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: OBJECTIVE. Our goal was to evaluate the long-term safety and efficacy of recombinant human α-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I. PATIENTS AND METHODS. All 45 patients who completed a 26-week, double-blind, placebocontrolled 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° ± 3.6°) 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Pediatrics is the property of American Academy of Pediatrics and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1542/peds.2007-3847
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      – Code: eng
        Text: English
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        PageCount: 12
        StartPage: 229
    Subjects:
      – SubjectFull: Mucopolysaccharidosis treatment
        Type: general
      – SubjectFull: Placebos
        Type: general
      – SubjectFull: Vital capacity (Respiration)
        Type: general
      – SubjectFull: Infusion therapy
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      – SubjectFull: Glycosaminoglycans
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      – SubjectFull: Apnea
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      – SubjectFull: Anaphylaxis
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      – SubjectFull: Respiratory infections
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      – SubjectFull: Immunoglobulins
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      – TitleFull: Long-term Efficacy and Safety of Laronidase in the Treatment of Mucopolysaccharidosis I.
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              Text: Jan2009
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