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Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency.

Wasserman RL, Melamed I, Stein MR, Engl W, Sharkhawy M, Leibl H, Puck J, Rubinstein A, Kobrynski L, Gupta S, Grant AJ, Ratnayake A, Richmond WG, Church J, Yel L, Gelmont D - J. Clin. Immunol. (2016)

Bottom Line: The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1-12 to approximately 1.50/subject-year after 30 months of treatment.The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies.Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.

View Article: PubMed Central - PubMed

Affiliation: Allergy Partners of North Texas Research, Dallas, TX, USA.

ABSTRACT

Purpose: Treatment of primary immunodeficiency diseases (PIDD) with subcutaneous (SC) infusions of IgG preceded by injection of recombinant human hyaluronidase (rHuPH20) (IGHy) to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies.

Methods: Subjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous (IV) dose, facilitated by prior injection of 75 U/g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased (ramped-up) to a 3- or 4-week schedule.

Results: Eighty-three subjects (24 < 18 years; 59 ≥ 18 years) received 2729 infusions (excluding ramp-up) at a mean dose of 0.155 g/kg/week in the pivotal and 0.156 g/kg/week in the extension study. IGHy exposure exceeded 30 months in 48 subjects. During 187.7 subject-years of IGHy exposure, 2005 adverse events (AEs) (10.68 per subject-year) occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1-12 to approximately 1.50/subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160. The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years.

Conclusions: Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.

No MeSH data available.


Related in: MedlinePlus

Disposition of subjects
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Fig1: Disposition of subjects

Mentions: A total of 89 subjects, 46 male and 43 female, at 14 sites in the USA and Canada enrolled in the pivotal study. Age at enrollment ranged from 4 to 78 years. Eighty-seven (87) subjects received IGIV for a 3-month period either in epoch 1 (n = 56) or during a previous study (n = 31). Eighty-three (83) subjects (24 < 18 years and 59 ≥ 18 years) continued on to epoch 2 of IGHy treatment. Sixty-six (66) subjects at 11 sites rolled over into the extension study: 63 continued on IGHy and 3 on IGIV treatment. For details of subject demographics and disposition including age groups, refer to the online supplementary material Table E1 and Fig. 1.Fig. 1


Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency.

Wasserman RL, Melamed I, Stein MR, Engl W, Sharkhawy M, Leibl H, Puck J, Rubinstein A, Kobrynski L, Gupta S, Grant AJ, Ratnayake A, Richmond WG, Church J, Yel L, Gelmont D - J. Clin. Immunol. (2016)

Disposition of subjects
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940441&req=5

Fig1: Disposition of subjects
Mentions: A total of 89 subjects, 46 male and 43 female, at 14 sites in the USA and Canada enrolled in the pivotal study. Age at enrollment ranged from 4 to 78 years. Eighty-seven (87) subjects received IGIV for a 3-month period either in epoch 1 (n = 56) or during a previous study (n = 31). Eighty-three (83) subjects (24 < 18 years and 59 ≥ 18 years) continued on to epoch 2 of IGHy treatment. Sixty-six (66) subjects at 11 sites rolled over into the extension study: 63 continued on IGHy and 3 on IGIV treatment. For details of subject demographics and disposition including age groups, refer to the online supplementary material Table E1 and Fig. 1.Fig. 1

Bottom Line: The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1-12 to approximately 1.50/subject-year after 30 months of treatment.The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies.Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.

View Article: PubMed Central - PubMed

Affiliation: Allergy Partners of North Texas Research, Dallas, TX, USA.

ABSTRACT

Purpose: Treatment of primary immunodeficiency diseases (PIDD) with subcutaneous (SC) infusions of IgG preceded by injection of recombinant human hyaluronidase (rHuPH20) (IGHy) to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies.

Methods: Subjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous (IV) dose, facilitated by prior injection of 75 U/g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased (ramped-up) to a 3- or 4-week schedule.

Results: Eighty-three subjects (24 < 18 years; 59 ≥ 18 years) received 2729 infusions (excluding ramp-up) at a mean dose of 0.155 g/kg/week in the pivotal and 0.156 g/kg/week in the extension study. IGHy exposure exceeded 30 months in 48 subjects. During 187.7 subject-years of IGHy exposure, 2005 adverse events (AEs) (10.68 per subject-year) occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1-12 to approximately 1.50/subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160. The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years.

Conclusions: Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.

No MeSH data available.


Related in: MedlinePlus