dc.contributor.author |
Giugliani, R.
|
|
dc.contributor.author |
Harmatz, P.
|
|
dc.contributor.author |
Jones, S.A.
|
|
dc.contributor.author |
Mendelsohn, N.J.
|
|
dc.contributor.author |
Vellodi, A.
|
|
dc.contributor.author |
Qiu, Y.
|
|
dc.contributor.author |
Hendriksz, Christian J.
|
|
dc.contributor.author |
Vijayaraghavan, S.
|
|
dc.contributor.author |
Whiteman, D.A.H.
|
|
dc.contributor.author |
PAno, A.
|
|
dc.date.accessioned |
2017-03-14T11:20:32Z |
|
dc.date.available |
2017-03-14T11:20:32Z |
|
dc.date.issued |
2017-09 |
|
dc.description.abstract |
OBJECTIVES : This 109-week, nonrandomized, observational study of mucopolysaccharidosis II (MPS II) patients already
enrolled in the Hunter Outcome Survey (HOS) (NCT00882921), assessed the long-term immunogenicity of
idursulfase, and examined the effect of idursulfase-specific antibody generation on treatment safety (via infusion-
related adverse events [IRAEs]) and pharmacodynamics (via urinary glycosaminoglycans [uGAGs]).
METHODS : Male patients ≥5 years, enrolled in HOS regardless of idursulfase treatment status were eligible. Blood/
urine samples for anti-idursulfase antibody testing and uGAG measurement were collected every 12 weeks.
RESULTS : Due to difficulties in enrolling treatment-naïve patients, data collection was limited to 26 enrolled patients
of 100 planned patients (aged 5.1–35.5 years) all of whom were non-naïve to treatment. Fifteen (58%) patients
completed the study. There were 11/26 (42%) seropositive patients at baseline (Ab+), and 2/26 (8%)
others developed intermittent seropositivity by Week 13. A total of 9/26 patients (35%) had ≥1 sample positive
for neutralizing antibodies. Baseline uGAG levels were low due to prior idursulfase treatment and did not change
appreciably thereafter. Ab+patients had persistently higher uGAG levels at entry and throughout the study than
Ab− patients. Nine of 26 (34%) patients reported IRAEs. Ab+ patients appeared to have a higher risk of developing
IRAEs than Ab−patients. However, the relative risk was not statistically significant and decreased after adjustment
for age.
CONCLUSIONS : 50% of study patients developed idursulfase antibodies. Notably Ab+ patients had persistently higher average uGAG levels. A clear association between IRAEs and antibodies was not established. |
en_ZA |
dc.description.department |
Paediatrics and Child Health |
en_ZA |
dc.description.librarian |
am2017 |
en_ZA |
dc.description.sponsorship |
Shire (NCT00882921), Lexington,MA USA |
en_ZA |
dc.description.uri |
http://www.elsevier.com/locate/ymgmr |
en_ZA |
dc.identifier.citation |
Giugliani, R, Harmatz, P, Jones, SA, Mendelsohn, NJ, Vellodi, A, Qiu, Y, Hendriksz, CJ, Vijayaraghavan, S,, Whiteman, DAH & Pano, A 2017, 'Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients', Molecular Genetics and Metabolism Reports, vol. 12, pp. 2-7. |
en_ZA |
dc.identifier.issn |
2214-4269 |
|
dc.identifier.other |
10.1016/j.ymgmr.2017.01.014 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/59422 |
|
dc.language.iso |
en |
en_ZA |
dc.publisher |
Elsevier |
en_ZA |
dc.rights |
© 2017 Published by Elsevier Inc. This is an open access article under te CC BY-NC-ND license (
http://
creativecommons.org/li
censes/by-nc-nd/4.0/
). |
en_ZA |
dc.subject |
Neutralizing antibodies |
en_ZA |
dc.subject |
Idursulfase |
en_ZA |
dc.subject |
Hunter syndrome |
en_ZA |
dc.subject |
Enzyme replacement therapy |
en_ZA |
dc.subject |
Cognitive impairment |
en_ZA |
dc.subject |
Immunogenicity |
en_ZA |
dc.subject |
Glycosaminoglycans |
en_ZA |
dc.subject |
Infusion-related adverse event (IRAE) |
en_ZA |
dc.subject |
Mucopolysaccharidosis II (MPS II) |
en_ZA |
dc.subject |
Urinary glycosaminoglycan (uGAG) |
en_ZA |
dc.subject |
Hunter outcome survey (HOS) |
en_ZA |
dc.title |
Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients |
en_ZA |
dc.type |
Article |
en_ZA |