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Subcutaneous Immunoglobulin Replacement Therapy with Hizentra® is Safe and Effective in Two Infants with Immunodeficiency
AB16 Abstracts
SATURDAY
60
IgG Trough Levels are Poor Predictors of Infectious Outcomes in Pediatric Patients on Immunoglobulin Replacement M. Mahendra1, S. McGhee1,2; 1UCLA, Westwood, CA, 2Stanford University, Palo Alto, CA. RATIONALE: In patients with antibody deficiencies, immunoglobulin replacement therapy can be used to prevent increased rates of infections. The goal of this study is to investigate the correlation of IgG trough levels on infection and hospitalization rates in patients with primary antibody deficiencies on intravenous immunoglobulin therapy. METHODS: This retrospective study examined 63 charts of patients with primary antibody deficiencies seen at the UCLA pediatric primary immunodeficiency clinic. Approval for this study was given by the Institutional Review Board at UCLA. Using multivariate regression, the relationship between IgG trough levels, infections, and hospitalizations was examined. RESULTS: There is a modest correlation (R250.14) between IgG concentrations and infection rate. The mean IgG trough level was negatively correlated (p5.01) with infection. There was no statistically significant relationship (p>0.05) between mean IgG trough level and hospitalizations. CONCLUSIONS: In patients with primary antibody deficiencies receiving intravenous immunoglobulin therapy, IgG trough levels are poor predictors of infectious outcomes. Dosing of replacement immunoglobulin therapy should be adjusted to target clinical outcomes.
61
Subcutaneous Immunoglobulin Replacement Therapy with HizentraÒ is Safe and Effective in Two Infants with Immunodeficiency J. L. Gallagher, N. C. Patel; Carolinas Medical Center, Charlotte, NC. RATIONALE: Administration of subcutaneous IgG (SCIG) is an effective and safe treatment for children and adults because it does not require venous access, has fewer side effects than intravenous IgG (IVIG) administration, and can be administered in a home setting. HizentraÒ (IgPro20, recently approved in the US) is a 20% liquid IgG product for subcutaneous administration that has been studied in adults and children greater than two years of age. There is limited data on the safety and efficacy of HizentraÒ in infants less than two years of age. METHODS: We describe two infants, one with Comel-Netherton syndrome and impaired response to vaccines and another with Turner syndrome and hypogammaglobulinemia, receiving IgG replacement therapy. RESULTS: Due to poor venous access, both infants were switched after three doses of IVIG to dose-equivalent weekly SCIG administration of HizentraÒ for 31 and 20 weeks respectively. Individual infusion time for both patients was one hour. Local reaction was mild in the infant with Comel-Netherton syndrome and absent in the infant with Turner syndrome. No serious adverse events were reported. IgG levels achieved with HizentraÒ increased an average of 25% compared to levels with IVIG. One serious bacterial infection (Escherichia coli urinary tract infection) occurred in the infant with Comel-Netherton syndrome. The rates of non-serious infections were 1.19/year and 0.53/year in the infants with Comel-Netherton syndrome and Turner syndrome, respectively. CONCLUSIONS: HizentraÒ is both safe and effective in infants less than two years of age, and is a suitable alternative in infants with difficult intravenous access.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
62
Desensitization Approach Using High-Concentration Subcutaneous Immunoglobulin in a Bruton's-Like Patient With a Previous Anaphylactic Reaction to Intravenous Immunoglobulin T. Prince, M. Gettys; The Allergy Asthma and Sinus Center, Maryville, TN. RATIONALE: Anaphylactic reactions to intravenous immunoglobulin (IVIG) rarely occur, but desensitization using high-concentration subcutaneous immunoglobulin (SCIG) may increase tolerability. No standard method exists for desensitization using SCIG. We report a SCIG desensitization approach in a Bruton’s-like patient intolerant to IVIG. METHODS: A 58-year-old female with a history of bronchiectasis and pneumonia-related hospitalizations, referred for persistent rhinitis, had a total absence of all immunoglobulins, leukopenia, and low B-cells. RESULTS: She was diagnosed with Bruton’s-like disease, treated with a single dose of 30 g (500 mg/kg) IVIG (Gammagard Liquid 10%), and experienced an anaphylactic reaction (facial flushing, nausea, abdominal cramping, urge to defecate, dyspnea) 9 minutes into the 30 ml/h infusion. After further questioning, she revealed previous reactions to intramuscular immunoglobulin for foreign travel. She was subsequently premedicated (prednisone, montelukast, cetirizine), then infused in a controlled setting with 10 g (163 mg/kg) undiluted 16% SCIG (Vivaglobin) over 4.5 hours using the slowest-rate tubing available. Premedication was discontinued after the 2nd infusion. Following 3 more in-office Vivaglobin infusions, the patient continued weekly 10 g/wk at-home infusions administered over 1.5 hours. After 16 months, she was switched to 10 g/wk 20% SCIG (Hizentra) without premedication, and had no observed adverse reactions. Compared with Vivaglobin, the number of infusion sites was reduced from 4 to 3, and total infusion volume was reduced from 63 ml to 50 ml due to the higher IgG concentration of Hizentra. CONCLUSIONS: SCIG desensitization was successful in a patient initially intolerant to IVIG. This approach, using only Hizentra, is currently underway in another patient.
63
Immunoglobulin Replacement Therapy: A 20 Year Review and Current Update M. Saeedian1, I. Randhawa2; 1UCLA, Los Angeles, CA, 2UC Irvine, Miller Children’s Hospital, Irvine, CA. RATIONALE: The expansion of immunoglobulin replacement to multiple disease entities marks a decades long advancement in immune therapy. Parallel to its extension, the characteristics and composition of immunoglobulin products have diversified. The aim of this study is to summarize a twenty year comprehensive literature review of current commercially available immunoglobulin products particularly examining individual product properties in a comparative format. METHODS: The literature review was performed utilizing Pubmed and Ovid over two decades. Both authors reviewed the obtained references for acceptable quality and references were narrowed down based on criteria of randomized clinical and therapeutic trials. RESULTS: Product specific characteristics in terms of purification strategy, stabilizers, composition, and viral inactivation are present among the specific immunoglobulin products investigated. Such differing characteristics manifest in variable clinical safety and efficacy comparative product analyses. Subcutaneous immunoglobulin therapy may be an alternative to IV immunoglobulin therapy in subgroups of patients with equal efficacy and lower systemic adverse events. CONCLUSIONS: Few comprehensive clinical synopses are available to clearly demonstrate differences in IV immunoglobulin products despite a widespread clinical use of therapy. This review defines significant characteristics of individual immunoglobulin products noting important differences in product development and application allowing informed clinical decisions to match a product with patients’ risk factors and comorbidity. This balance approach to gammaglobulin replacment therapy is imperative in producing the highest clinical efficacy and lowest adverse events.
SATURDAY
60
IgG Trough Levels are Poor Predictors of Infectious Outcomes in Pediatric Patients on Immunoglobulin Replacement M. Mahendra1, S. McGhee1,2; 1UCLA, Westwood, CA, 2Stanford University, Palo Alto, CA. RATIONALE: In patients with antibody deficiencies, immunoglobulin replacement therapy can be used to prevent increased rates of infections. The goal of this study is to investigate the correlation of IgG trough levels on infection and hospitalization rates in patients with primary antibody deficiencies on intravenous immunoglobulin therapy. METHODS: This retrospective study examined 63 charts of patients with primary antibody deficiencies seen at the UCLA pediatric primary immunodeficiency clinic. Approval for this study was given by the Institutional Review Board at UCLA. Using multivariate regression, the relationship between IgG trough levels, infections, and hospitalizations was examined. RESULTS: There is a modest correlation (R250.14) between IgG concentrations and infection rate. The mean IgG trough level was negatively correlated (p5.01) with infection. There was no statistically significant relationship (p>0.05) between mean IgG trough level and hospitalizations. CONCLUSIONS: In patients with primary antibody deficiencies receiving intravenous immunoglobulin therapy, IgG trough levels are poor predictors of infectious outcomes. Dosing of replacement immunoglobulin therapy should be adjusted to target clinical outcomes.
61
Subcutaneous Immunoglobulin Replacement Therapy with HizentraÒ is Safe and Effective in Two Infants with Immunodeficiency J. L. Gallagher, N. C. Patel; Carolinas Medical Center, Charlotte, NC. RATIONALE: Administration of subcutaneous IgG (SCIG) is an effective and safe treatment for children and adults because it does not require venous access, has fewer side effects than intravenous IgG (IVIG) administration, and can be administered in a home setting. HizentraÒ (IgPro20, recently approved in the US) is a 20% liquid IgG product for subcutaneous administration that has been studied in adults and children greater than two years of age. There is limited data on the safety and efficacy of HizentraÒ in infants less than two years of age. METHODS: We describe two infants, one with Comel-Netherton syndrome and impaired response to vaccines and another with Turner syndrome and hypogammaglobulinemia, receiving IgG replacement therapy. RESULTS: Due to poor venous access, both infants were switched after three doses of IVIG to dose-equivalent weekly SCIG administration of HizentraÒ for 31 and 20 weeks respectively. Individual infusion time for both patients was one hour. Local reaction was mild in the infant with Comel-Netherton syndrome and absent in the infant with Turner syndrome. No serious adverse events were reported. IgG levels achieved with HizentraÒ increased an average of 25% compared to levels with IVIG. One serious bacterial infection (Escherichia coli urinary tract infection) occurred in the infant with Comel-Netherton syndrome. The rates of non-serious infections were 1.19/year and 0.53/year in the infants with Comel-Netherton syndrome and Turner syndrome, respectively. CONCLUSIONS: HizentraÒ is both safe and effective in infants less than two years of age, and is a suitable alternative in infants with difficult intravenous access.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
62
Desensitization Approach Using High-Concentration Subcutaneous Immunoglobulin in a Bruton's-Like Patient With a Previous Anaphylactic Reaction to Intravenous Immunoglobulin T. Prince, M. Gettys; The Allergy Asthma and Sinus Center, Maryville, TN. RATIONALE: Anaphylactic reactions to intravenous immunoglobulin (IVIG) rarely occur, but desensitization using high-concentration subcutaneous immunoglobulin (SCIG) may increase tolerability. No standard method exists for desensitization using SCIG. We report a SCIG desensitization approach in a Bruton’s-like patient intolerant to IVIG. METHODS: A 58-year-old female with a history of bronchiectasis and pneumonia-related hospitalizations, referred for persistent rhinitis, had a total absence of all immunoglobulins, leukopenia, and low B-cells. RESULTS: She was diagnosed with Bruton’s-like disease, treated with a single dose of 30 g (500 mg/kg) IVIG (Gammagard Liquid 10%), and experienced an anaphylactic reaction (facial flushing, nausea, abdominal cramping, urge to defecate, dyspnea) 9 minutes into the 30 ml/h infusion. After further questioning, she revealed previous reactions to intramuscular immunoglobulin for foreign travel. She was subsequently premedicated (prednisone, montelukast, cetirizine), then infused in a controlled setting with 10 g (163 mg/kg) undiluted 16% SCIG (Vivaglobin) over 4.5 hours using the slowest-rate tubing available. Premedication was discontinued after the 2nd infusion. Following 3 more in-office Vivaglobin infusions, the patient continued weekly 10 g/wk at-home infusions administered over 1.5 hours. After 16 months, she was switched to 10 g/wk 20% SCIG (Hizentra) without premedication, and had no observed adverse reactions. Compared with Vivaglobin, the number of infusion sites was reduced from 4 to 3, and total infusion volume was reduced from 63 ml to 50 ml due to the higher IgG concentration of Hizentra. CONCLUSIONS: SCIG desensitization was successful in a patient initially intolerant to IVIG. This approach, using only Hizentra, is currently underway in another patient.
63
Immunoglobulin Replacement Therapy: A 20 Year Review and Current Update M. Saeedian1, I. Randhawa2; 1UCLA, Los Angeles, CA, 2UC Irvine, Miller Children’s Hospital, Irvine, CA. RATIONALE: The expansion of immunoglobulin replacement to multiple disease entities marks a decades long advancement in immune therapy. Parallel to its extension, the characteristics and composition of immunoglobulin products have diversified. The aim of this study is to summarize a twenty year comprehensive literature review of current commercially available immunoglobulin products particularly examining individual product properties in a comparative format. METHODS: The literature review was performed utilizing Pubmed and Ovid over two decades. Both authors reviewed the obtained references for acceptable quality and references were narrowed down based on criteria of randomized clinical and therapeutic trials. RESULTS: Product specific characteristics in terms of purification strategy, stabilizers, composition, and viral inactivation are present among the specific immunoglobulin products investigated. Such differing characteristics manifest in variable clinical safety and efficacy comparative product analyses. Subcutaneous immunoglobulin therapy may be an alternative to IV immunoglobulin therapy in subgroups of patients with equal efficacy and lower systemic adverse events. CONCLUSIONS: Few comprehensive clinical synopses are available to clearly demonstrate differences in IV immunoglobulin products despite a widespread clinical use of therapy. This review defines significant characteristics of individual immunoglobulin products noting important differences in product development and application allowing informed clinical decisions to match a product with patients’ risk factors and comorbidity. This balance approach to gammaglobulin replacment therapy is imperative in producing the highest clinical efficacy and lowest adverse events.