title: Diagnosis, quality of life, and treatment of patients with Hunter syndrome in the French healthcare system: a retrospective observational study.
abstract: BACKGROUND
  Mucopolysaccharidosis II (MPS II) is associated with a broad spectrum of chronic and progressive, life-limiting symptoms. Idursulfase is approved for MPS II enzyme replacement therapy (ERT) in over 50 countries. This retrospective study evaluated the MPS II burden, organization of clinical care, and effects of idursulfase treatment on the disease in France.
  
  
  METHODS
  MPS II patients who had received idursulfase ERT in the French healthcare system were enrolled. In addition to clinician and patient questionnaires, the Clinical Global Impression-Improvement (CGI-I); Patient Global Impression-Improvement (PGI-I); KIDSCREEN-27, and EuroQoL-5D for adult patients scales were used to assess quality of life (QoL) and efficacy.
  
  
  RESULTS
  Fifty-two patients were enrolled from 5 sites in France. The majority of patients (69.2%) presented a severe MPS II phenotype with progressive neurocognitive impairment. Major impacts on QoL were apparent, with at least 1 member of the family having to reorganize working hours (45.5%) or to stop working (22.7%). KIDSCREEN-27 and EuroQoL-5D scale scores were well below those for referent (control) populations. Most families (70.0%) experienced a diagnostic delay of at least 3 years after the initial observation of symptoms. The MPS II diagnosis was often delivered without adequate sensitivity, psychological support, or comprehensive information about the disease. The study population had received a mean of 3.8 ± 1.3 years ERT. Forty-four percent of patients with the attenuated phenotype (without progressive neurocognitive impairment) showed symptom improvement during both the first year (Period 1) and from the end of the first year of treatment to "the present" (Period 2), as measured by CGI-I/PGI-I. 30.3% and 9.1% of severe patients experienced symptom improvement during Periods 1 and 2, respectively, while 63.6% and 51.5% displayed no change. The most common adverse reactions reported were skin rash and other infusion-associated reactions.
  
  
  CONCLUSIONS
  MPS II adversely affects multiple domains of QoL for patients and families, requiring multiple healthcare services and social aid programs. The majority of patients with either phenotype experienced either improvement or stability in their symptoms during the first year of ERT, but this was clearly less so for patients with the severe phenotype after the first year of treatment.
authors.affiliation: Centre de Référence des Maladies Héréditaires du Métabolisme, Hospices Civils de Lyon Hôpital Femme Mère Enfants, Bron, France. nathalie.guffon-fouilhoux@chu-lyon.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.affiliation: Service de Neurologie Pédiatrique, Centre de Référence des Maladies Lysosomales, CHU Trousseau, APHP, Paris, France. benedicte.heron@trs.aphp.fr.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Heron
authors.affiliation: Service de Neurologie Pédiatrique, Centre de Référence des Maladies Héréditaires du Métabolisme. Hôpital d'Enfants, CHU La Timone, Marseille, France. bchabrol@ap-hm.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.affiliation: Centre de Référence des Maladies Héréditaires du Métabolisme, Service de Médecine Infantile, CHU Brabois Enfants, Vandoeuvre les Nancy, France. f.feillet@chu-nancy.fr.
authors.forename: François
authors.initials: F
authors.lastname: Feillet
authors.affiliation: Shire, 88 rue du Dôme, Boulogne Billancourt, 92100, France. vincent.montauban@free.fr.|Current address: Baxter Healthcare, 6 Avenue Louis Pasteur - BP 56, Maurepas, 78311, France. vincent.montauban@free.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Montauban
authors.affiliation: Centre de Référence Maladies Métaboliques de l'enfant et de l'adulte, Hôpital Universitaire Necker-Enfants Malades et Institut IMAGINE, Paris, France. vassili.valaya@nck.aphp.fr.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D003695:Delivery of Health Care; D056947:Enzyme Replacement Therapy; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007066:Iduronate Sulfatase / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008875:Middle Aged; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D011788:Quality of Life; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D007066:Iduronate Sulfatase; C517982:idursulfase