require life-long immunoglobulin replacement therapy. Conveniently, .... ing LLC, King of Prussia, PA, 8Research and Development, CSL Behring. K.K., Tokyo ...
AB180 Abstracts
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Safety and Efficacy Of Biweekly HizentraÒ Administration In Patients With Primary Immunodeficiency Diseases: A Retrospective Single-Center Study Clare Malcolmson, Dr. Alison Jones; Great Ormond Street Hospital, London, United Kingdom. RATIONALE: Patients with primary immunodeficiency diseases (PID) require life-long immunoglobulin replacement therapy. Conveniently, subcutaneous IgG (SCIG) can be self-administered at home. This study retrospectively evaluated the safety and efficacy of biweekly (Q2W) administration of a 20% SCIG (HizentraÒ) in clinical practice. METHODS: Children and adults with PID received their first one or two doses of HizentraÒ in hospital, and subsequent doses at home. Safety and efficacy data were based on measurements made during clinic visits and retrospectively collected feedback, and analyzed using descriptive statistics. RESULTS: 54 patients (75.9% male, median age [range] 7.8 [1–18.8] years) received HizentraÒ weekly (n530), biweekly (n522) or once every 10 days (n52). Total monthly HizentraÒ doses were similar in the biweekly and weekly groups (mean [SD] 674.8 [160.9] versus 662.7 [174.8] mg/kg, respectively). Despite baseline age differences between biweekly and weekly groups (median age [range] 3.2 [1–10.9] versus 12.3 [3.5–18.8] years, respectively), on-treatment trough serum IgG levels were similar (mean [SD]; 10.5 [2.4] versus 12.2 [3.4] g/L, respectively). Among 37 patients analyzed for safety, treatment-related adverse events (biweekly: 1/14; weekly: 2/21) were rare, with no serious adverse events. Median observation periods were 9.5 and 10 months (biweekly and weekly groups, respectively). CONCLUSIONS: In this population, the efficacy and safety profile of biweekly HizentraÒ administration was comparable to that of weekly administration. Flexibility offered by weekly or biweekly HizentraÒ administration schedules allows patients to adapt therapy to their lifestyle; these alternatives should be considered by physicians. Young children, who require smaller doses, could particularly benefit from less frequent biweekly injections.
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Long-Term Tolerability and Safety Of FacilitatedSubcutaneous Infusion Of Human Immune Globulin G (IgG), 10%, and Recombinant Human Hyaluronidase (rHuPH20) (IGHy): A Phase 3 Extension Study In Patients With Primary Immunodeficiencies (PIs) Dr. Isaac Reuven Melamed, MD1, Dr. Richard L. Wasserman, MD, PhD, FAAAAI2, Dr. Mark Stein, MD, FAAAAI3, Dr. Arye Rubinstein, MD, FAAAAI4, Dr. Jennifer M. Puck, MD5, Sudhir Gupta, MD, PhD, FAAAAI6, Werner Engl7, Dr. Heinz Leibl, PhD7, Dr. Leman Yel, MD, FAAAAI8, Dr. Richard I. Schiff, MD, PhD8; 1IMMUNOe Health Centers, Centennial, CO, 2DallasAllergyImmunology, Dallas, TX, 3Allergy Associates of the Palm Beaches, North Palm Beach, FL, 4Albert Einstein College of Medicine, Bronx, NY, 5Department of Pediatrics, University of California San Francisco and UCSF Benioff Children’s Hospital, San Francisco, CA, 6University of California, Irvine, Irvine, CA, 7Baxter BioScience, Vienna, Austria, 8Baxter BioScience, Westlake Village, CA. RATIONALE: In a phase 3 trial of IGHy in PI patients, rHuPH20 permitted mostly single-site infusion (every 3-4-week IgG dosing) with bioavailability/infusion rates comparable to intravenously administered IgG. We will report the final analysis of the long-term extension of the phase 3 study, with a duration of up to 3 years of treatment plus followup. METHODS: Sixty-six patients completing the phase 3 study enrolled in the extension study. Patients continued their pre-study IGHy dose/ frequency every 3-4 weeks. After 3 months, some patients switched to 2week dosing to evaluate effects of shorter IGHy interval on trough IgG levels. From an interim analysis in April 2012, tolerability/safety after up to 3 years of treatment were evaluated. The IGHy study was followed by a 24-48 week observation period. RESULTS: Forty-nine patients completed the study. No patients withdrew due to drug-related reactions (ADRs). At interim analysis, no serious
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
ADRs were reported. Systemic ADRs/infusion rate50.10. Local adverse events/infusion rate50.17. Annual infection rate53.10. Of 2501 IGHy infusions, 97.6% had no administration changes (rate reduction/interruption/discontinuation) due to tolerability concerns/adverse events. Reducing the dosing interval from 4 to 2 weeks (same monthly dose) resulted in a 12% increase in trough IgG levels. Fifteen patients had binding anti-rHuPH20 antibodies with no associated AEs; no patients had neutralizing anti-rHuPH20 antibodies. No safety issues were observed during follow-up after IGHy discontinuation. CONCLUSIONS: IGHy was well tolerated and effective, with no serious ADRs for treatment periods up to 3 years plus 24-48-week follow-up after discontinuation of rHuPH20 exposure. The final analysis will be presented.
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Health-Related Quality Of Life Of Japanese Patients With Primary Immunodeficiency Diseases Receiving IgPro20, a 20% Liquid Subcutaneous Immunoglobulin (HizentraÒ) Prof. Hirokazu Kanegane, MD, PhD1, Prof. Kohsuke Imai, MD, PhD2, Prof. Masafumi Yamada, MD, PhD3, Prof. Hidetoshi Takada, MD, PhD4, Prof. Tadashi Ariga, MD, PhD3, Prof. Ataru Igarashi, PhD5, Prof. Kiichiro Tsutani, MD, PhD5, Dr. Martin Bexon, MD6, Dr. Mikhail Rojavin, PhD7, Ms. Midori Kobayashi, BSPharm, MBA8, Dr. John-Philip Lawo, PhD9, Mr. Art Zbrozek, RPh, MSc, MBA10, Prof. Shigeaki Nonoyama, MD, PhD11, Prof. Toshiro Hara, MD, PhD4, Prof. Toshio Miyawaki, MD, PhD1; 1Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan, 2Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University, Tokyo, Japan, 3Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 4 Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 5Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan, 6Clinical Research and Development, CSL Behring AG, Berne, Switzerland, 7Clinical Research and Development, CSL Behring LLC, King of Prussia, PA, 8Research and Development, CSL Behring K.K., Tokyo, Japan, 9CSL Behring GmbH, Marburg, Germany, 10CSL Behring LLC, King of Prussia, PA, 11Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan. RATIONALE: This study aimed at evaluating health-related quality of life (HRQL) of Japanese patients with primary immunodeficiencies (PID) receiving a 20% liquid immunoglobulin (HizentraÒ) administered subcutaneously (SCIG) compared to preceding intravenous IgG (IVIG) treatment. METHODS: Twenty-four patients with PID treated with IVIG at 3–4week intervals, received 3 further IVIG doses before they were switched to a dose-equivalent weekly SCIG for 24 weeks. Questionnaires on HRQL (‘‘Life Quality Index’’ [LQI] and Treatment Satisfaction) were completed by the patient/patient representative at baseline after IVIG therapy (Week 1), at the end of the wash-in/wash-out period (Week 12) and at the end of the SCIG efficacy period (Week 24). RESULTS: As per study design, after training period, all patients received all but every fourth infusion at home. At Week 24, 58.3% of patients were self-administering HizentraÒ, the rest (mostly children) received infusions from their relatives. Mean (SD) scores of treatment satisfaction (0, worst, 100, best) increased from 66.7 (22.52) at baseline to 73.9 (21.22) at Week 24. Mean (SD) LQI scores were 53.7 (19.53) at baseline and 71.5 (15.14) at Week 24 and showed an improvement in all subcategories, with the largest change observed in ‘‘Costs and Therapy Setting’’. CONCLUSIONS: HizentraÒ demonstrated a positive effect on HRQL in Japanese PID patients. In addition to the known benefits of SCIG therapy such as home-based self-administration, dosing flexibility, good tolerability, absence of the ‘‘wear-off’’ effects typical of IVIG dosing cycles, and following its use in Europe and the US, HizentraÒ administration resulted in high treatment satisfaction in Japanese patients.
