Table 2.

Mucopolysaccharidosis Type II: Targeted Treatment

Targeted TreatmentDosageBenefitsConsiderations
Idursulfase (Elaprase®) enzyme replacement therapy (ERT) 1Intravenous weekly dose of 0.5 mg/kg 2, 3
  • Survival in idursulfase-treated persons is higher than in those who are untreated. 4
  • Idursulfase has positive effects on functional capacity (distance walked in 6 mins & forced vital capacity), liver & spleen volumes, & urine GAG excretion. 5
  • ERT improves somatic signs & symptoms of disease in all persons, incl infants age <1 year & persons w/early progressive MPS II phenotype. 6
  • Long-term use of ERT is similarly effective in young (age 1.6-12 years at start of ERT) & older persons (age 12-27 years at start of ERT). 7
  • Since idursulfase does not cross blood-brain barrier, no effect on CNS disease is anticipated. 8
  • Infusion-related reactions are comparable to similar reactions seen w/other ERT products. 2, 9, 10

CNS = central nervous system; GAG = glycosaminoglycan

1.

A recombinant form of human iduronate 2-sulfatase that has been approved in the United States and the European Union

2.

Pre-treatment with anti-inflammatory drugs or antihistamines, as is often done for enzyme replacement therapy (ERT) in other conditions, is not suggested on the label for Elaprase®; however, if mild or moderate infusion reactions (e.g., dyspnea, urticaria, or systolic blood pressure changes of ≤20 mm Hg) cannot be ameliorated by slowing the infusion rate, the addition of treatment one hour before infusion with diphenhydramine and acetaminophen (or ibuprofen) to the regimen usually resolves the problem. Pre-treatment can typically be discontinued after six to ten weeks.

3.

Severe non-allergic anaphylactoid reactions such as major changes in blood pressure, wheezing, stridor, rigors, or drop in oxygen saturations should be immediately addressed by stopping the infusion and giving appropriate doses of subcutaneous epinephrine, intravenous (IV) diphenhydramine, and hydrocortisone or methylpredinsolone. Subsequent infusions should then be given at a significantly reduced rate with pre-treatment with prednisone 24 hours and eight hours before the infusion, diphenhydramine and acetaminophen or ibuprofen orally one hour before the infusion, and IV methylpredinsolone just before beginning the infusion.

4.
5.
6.
7.
8.

In order to overcome the limitations in the treatment of the central nervous system (CNS), intrathecal ERT and gene therapy are currently under investigation as future therapies [Motas et al 2016, Stapleton et al 2017]. Shire recently sponsored a Phase II/III clinical trial examining the use of intrathecal iduronate 2-sulfatase in young individuals with MPS II with CNS involvement (NCT02055118).

9.

The etiology of the more severe forms of these non-allergic reactions, referred to as anaphylactoid, is unknown. Current evidence suggests that anaphylactoid (as opposed to anaphylactic) reactions are not immune mediated [Mayer & Young 2006].

10.

Infusion reactions are generally mild and include brief, insignificant decreases or increases in heart rate, blood pressure, or respiratory rate; itching; rash; flushing; and headache. Mild reactions can usually be managed by slowing the infusion rate for several treatments and then slowly returning to the prior rate.

From: Mucopolysaccharidosis Type II

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