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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

Summary of all, related, or temporally associated AEs (excluding infections) by severity for subjects who developed anti-rHuPH20 antibodies (pivotal study including ramp-up and extension study)
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Related In: Results  -  Collection


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Fig2: Summary of all, related, or temporally associated AEs (excluding infections) by severity for subjects who developed anti-rHuPH20 antibodies (pivotal study including ramp-up and extension study)

Mentions: No subject developed neutralizing antibodies to rHuPH20. Low anti-rHuPH20 antibody titers were determined in PIDD subjects including those who, due to their underlying immunodeficiency syndrome, were incapable of producing any type of antibodies. As low anti-rHuPH20 antibody titers were also identified in normal healthy blood donors, titers <1:160 were considered to be consistent with passive transfer from IGSC and therefore ignored in subsequent analyses [26]. However, 13 subjects developed anti-rHuPH20 antibody titers ≥1:160 during the pivotal study. Titers ≥1:160 persisted (i.e., two or more consecutive values) in 6/11 subjects who rolled over into the extension study; another two subjects developed a single increase to 1:160 during the extension study. Anti-rHuPH20 antibody titers typically declined during continued IGHy treatment and thereafter further decreased during the safety follow-up on IGIV or IGSC (data not shown). Annual rates of total, systemic, and local AEs in subjects who developed anti-rHuPH20 antibodies ≥1:160 were similar before and after the first positive titer of anti-rHuPH20 antibodies ≥1:160 (Fig. 2).Fig. 2


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)

Summary of all, related, or temporally associated AEs (excluding infections) by severity for subjects who developed anti-rHuPH20 antibodies (pivotal study including ramp-up and extension study)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Summary of all, related, or temporally associated AEs (excluding infections) by severity for subjects who developed anti-rHuPH20 antibodies (pivotal study including ramp-up and extension study)
Mentions: No subject developed neutralizing antibodies to rHuPH20. Low anti-rHuPH20 antibody titers were determined in PIDD subjects including those who, due to their underlying immunodeficiency syndrome, were incapable of producing any type of antibodies. As low anti-rHuPH20 antibody titers were also identified in normal healthy blood donors, titers <1:160 were considered to be consistent with passive transfer from IGSC and therefore ignored in subsequent analyses [26]. However, 13 subjects developed anti-rHuPH20 antibody titers ≥1:160 during the pivotal study. Titers ≥1:160 persisted (i.e., two or more consecutive values) in 6/11 subjects who rolled over into the extension study; another two subjects developed a single increase to 1:160 during the extension study. Anti-rHuPH20 antibody titers typically declined during continued IGHy treatment and thereafter further decreased during the safety follow-up on IGIV or IGSC (data not shown). Annual rates of total, systemic, and local AEs in subjects who developed anti-rHuPH20 antibodies ≥1:160 were similar before and after the first positive titer of anti-rHuPH20 antibodies ≥1:160 (Fig. 2).Fig. 2

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