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Observational Study
. 2021 Jul;106(7):674-679.
doi: 10.1136/archdischild-2020-319040. Epub 2020 Nov 2.

Improvement in time to treatment, but not time to diagnosis, in patients with mucopolysaccharidosis type I

Roberto Giugliani  1 , Nicole Muschol  2 , Hillary A Keenan  3 , Mark Dant  4 , Joseph Muenzer  5
Affiliations
Observational Study

Improvement in time to treatment, but not time to diagnosis, in patients with mucopolysaccharidosis type I

Roberto Giugliani et al. Arch Dis Child. 2021 Jul.

Abstract

Objective: Early diagnosis and treatment initiation are important factors for successful treatment of mucopolysaccharidosis type I (MPS I). The purpose of this observational study was to assess whether age at diagnosis and time to first treatment for individuals with MPS I have improved over the last 15 years.

Study design: Data from the MPS I Registry (NCT00144794) for individuals with attenuated or severe disease who initiated therapy with laronidase enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT) between 1 January 2003 and 31 December 2017 were included.

Results: Data were available for 740 individuals with attenuated (n=291) or severe (n=424) MPS I (unknown n=25). Median age at diagnosis for attenuated disease did not change over time and ranged between 4.5 and 6 years of age while the median duration from diagnosis to first ERT decreased from 5.6 years before/during 2004 to 2.4 months in 2014-2017. For severe MPS I treated with HSCT, median age at diagnosis was less than 1 year and median time to first treatment was less than 3 months throughout the 15-year observation period.

Conclusions: Times to diagnosis and HSCT initiation for individuals with severe MPS I were consistent over time. For individuals with attenuated MPS I, the time to ERT initiation after diagnosis has improved substantially in the last 15 years, but median age at diagnosis has not improved. Efforts to improve early diagnosis in attenuated MPS I are needed to ensure that patients receive appropriate treatment at the optimal time.

Keywords: metabolic; monitoring; multidisciplinary team-care; therapeutics.

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Conflict of interest statement

Competing interests: RG has received consultant/speaker honoraria/fees and/or served on advisory boards for Actelion, Amicus, Biomarin, Inventiva, RegenxBio, Sanofi Genzyme, Sobi, Takeda and Ultragenyx, conducts contracted research for BioMarin, JCR, Lysogene, RegenxBio, Sanofi Genzyme, Takeda, and Ultragenyx and is a member of the International Board of Advisors of the MPS I Registry. NM is a consultant for Biomarin, Sanofi Genzyme, Lysogene, Shire and Sobi, has received grants/research support from Amicus, Biomarin, Sanofi Genzyme and Shire and has received honoraria and/or travel grants from Actelion, Amicus, BioMarin, Chiesi Farmaceutici S.p.A., Sanofi Genzyme and Shire. HK was an employee of Sanofi Genzyme at the time of the study.MD has received consultant/speaker honoraria and/or travel grants from Biomarin, Sanofi Genzyme, Regenxbio, Bluebird Bio, Ultragenyx. JM received consultant/speaker honoraria/fees and served on advisory boards for BioMarin, Denali, Eloxx, RegenxBio, Sangamo, Sanofi Genzyme and Shire, is a PI for a Phase I/II and Phase II/III intrathecal enzyme replacement clinical trials for MPS II and a Phase I/II gene editing clinical trial for MPS II and is a member of the International Board of Advisors of the MPS I Registry.

Figures

Figure 1
Figure 1
Characteristics of HSCT over time for individuals enrolled in the MPS I Registry. The type of transplant performed showing the source of stem cells is shown in (A). Use of ERT either before or immediately after transplant is shown in (B). ERT, enzyme replacement therapy; HSCT, haematopoietic stem cell transplants; MPS I, mucopolysaccharidosis type I.
Figure 2
Figure 2
Median age in years at MPS I diagnosis by year interval for individuals with severe (blue) or attenuated (red) MPS I receiving ERT as primary therapy. Global distribution is shown in panel (A). Regional distributions are shown for North America (B) and Europe (C). Individual medians are shown at the base of each bar and individual n’s are shown above the bars. ERT, enzyme replacement therapy; MPS I, mucopolysaccharidosis type I.
Figure 3
Figure 3
Median age in years at MPS I diagnosis by year interval for individuals with severe MPS I receiving HSCT as primary therapy. Global distribution is shown in panel (A). Regional distributions are shown for North America (B) and Europe (C). Individual medians are shown at the base of each bar and individual n’s are shown above the bars. ERT, enzyme replacement therapy; HSCT, haematopoietic stem cell transplants; MPS I, mucopolysaccharidosis type I.
Figure 4
Figure 4
Median duration from diagnosis to first ERT treatment by year interval for individuals with severe (blue) or attenuated (red) MPS I receiving ERT as primary therapy. Global distribution is shown in panel (A). Regional distributions are shown for North America (B) and Europe (C). Individual medians are shown at the base of each bar and individual n’s are shown at top of bars. ERT, enzyme replacement therapy; MPS I, mucopolysaccharidosis type I.
Figure 5
Figure 5
Median duration from diagnosis to first HSCT treatment by year interval for individuals with severe MPS I receiving HSCT as primary therapy. Global distribution is shown. HSCT, haematopoietic stem cell transplants; MPS I, mucopolysaccharidosis type I.
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