Tolerability of Human Immunoglobulin 10% Administered Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Primary Immunodeficiency Disease (PIDD) Patients

S A T U R D A Y 43 Differences in Ig Replacement Therapy Dosing in Patients with Common Variable Immunodeficiency in Europe: Results from the ESID Database B. Gathmann, N. Mahlaoui, K. Warnatz, T. W. Kuijpers, S. S. Kilic, V. Thon, P. D. Arkwright, D. Kumararatne, A. Exley, M. Borte, A. Jones, B. H. Belohradsky, U. Baumann, N. K€ut€ukc€uler, T. Witte, C. Feighery, P. Wagstr€om, H. Longhurst, R. Linde, H. Ritterbusch, E. Farmaki, A. Sediva, E. Papadopoulou-Alataki, Z. Panahloo, B. Grimbacher; Centre of Chronic Immunodeficiency (CCI), Univ Medical Center Freiburg and Univ of Freiburg, Freiburg, GERMANY, CEREDIH: The French PID study group, Unit e d’Immuno-H ematologie & Rhumatologie p ediatriques, Hopital NeckerEnfants Malades, Paris, FRANCE, Emma Children’s Hospital, Academic Medical Center (AMC), Amsterdam, NETHERLANDS, Uludag Univ Medical Faculty, Bursa, TURKEY, Masaryk Univ Medical Faculty, St. Anne Univ Hospital, Brno, CZECH REPUBLIC, Univ of Manchester, Manchester, UNITED KINGDOM, Cambridge Univ Hospital NHS Trust (Addenbrooke’s), Cambridge, UNITED KINGDOM, Cambridge Univ Health Partners, Papworth Hospital NHS Foundation Trust, Cambridge, UNITED KINGDOM, Children’s Hospital, Municipal Hospital ’St Georg’, Academic Teaching Hospital of the Univ of Leipzig, Leipzig, GERMANY, Institute of Child Health/Great Ormond Street Hospital, London, UNITEDKINGDOM, Dr v. Haunersches Kinderspital, Ludwig Maximilians Univ, Munich, GERMANY, Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, GERMANY, Ege Univ, Faculty of Medicine, Dept of Pediatric Immunology, Bornova, Izmir, TURKEY, Department of Clinical Immunology, Hannover Medical School, Hannover, GERMANY, Department of Immunology, Trinity College Dublin & St. James’ Hospital, Dublin, IRELAND, Ryhov County Hospital, Jonkoping, SWEDEN, Barts and the London NHS Trust, London, UNITED KINGDOM, J. W. Goethe Univ Hospital, Immunodeficiency Unit, Department of Pediatrics III, Frankfurt, GERMANY, Pediatric Immunology Referral Center, 1st Dept of Pediatrics, Aristotle Univ of Thessaloniki, Thessaloniki, GREECE, Department of Immunology, Univ Hospital Motol, Prague, CZECH REPUBLIC, Aristotle Univ of Thessaloniki, Medical School, Fourth Department of Pediatrics, Papageorgiou Hospital, Thessaloniki, GREECE, Medical Science Department, CSL Behring, Haywards Heath, UNITED KINGDOM, Royal Free Hospital & Univ College London, London, UNITED KINGDOM. RATIONALE:Commonvariable immunodeficiency (CVID) is characterised by low levels of serum immunoglobulins and increased susceptibility to infections. Standard therapy for patients is immunoglobulin (Ig) replacement. METHODS: In a retrospective analysis by country, we analysed CVID patients within the ESID Database for Primary Immunodeficiencies. Actual dosing with intravenous (IVIg) and subcutaneous (SCIg) products was compared to the recommended dose. We used 600 mg/kgBW/month as the recommended dose, as this is the midpoint between the recommended 400 and 800 mg/kgBW/month. Results represent the median percentage difference from this figure for IVIg (n5547 patients), SCIg (n5273) and total Ig patients (IVIg and/or SCIg route, n5647) for each country. RESULTS: There was wide regional variation in values for IVIg (p<0.001), SCIg (p50.004) and total Ig patients (p<0.001). The majority of countries prescribed doses lower than 600 mg/kgBW/month for IVIg such as Czech Republic (-46%) and Germany (-43%). The Netherlands (-5%) and Greece (+5%) showed the least variation. The prescribed doses for SCIg showed a similar picture, with the lowest doses in Czech Republic (-64%), Germany (-32%), France (-25%), the UK (-22%) and Sweden (-16%), whilst dosing levels were slightly higher only in Greece (+8%). Overall, the variations in dosing were similar with IVIg and SCIg (median: -22% vs. -26%; p50.02). CONCLUSIONS:This analysis indicates awide regional variation in dosing of Ig replacement therapy across Europe which requires further investigation of clinical phenotypes, adjunctive treatments (e.g., antibiotics), Ig serum levels achieved, and, most importantly, clinical outcomes. 44 Tolerability of Human Immunoglobulin 10% Administered Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Primary Immunodeficiency Disease (PIDD) Patients D. Gelmont, R. L. Wasserman, I. Melamed, M. Stein, A. Rubinstein, B. McCoy, W. Engl, H. Leibl, R. I. Schiff, W. J. Grossman; Baxter BioScience, Westlake Village, CA, DallasAllergyImmunology, Dallas, TX, Immunoe Health Centers, Centennial,, CO, Allergy Associates of the Palm Beaches, North Palm Beach, FL, Albert Einstein College of Medicine and Montefiore Hospital, Bronx, NY, Baxter BioScience, Vienna, AUSTRIA. RATIONALE: Intravenous (IV) and subcutaneous (SC) routes of immunoglobulin (IG) administration have both advantages and disadvantages. One disadvantage of IGSC therapy is the small volumes that can be administered subcutaneously, requiring multiple infusion sites and frequent administrations. rHuPH20 is a permeation enhancer that increases systemic absorption of SC infused fluids. This Phase 3 study evaluated the tolerability of rHuPH20-enabled 10% IGSC infusions at rates and frequencies equivalent to IGIV administration in PIDD patients. METHODS: PIDD patients were injected SC with 75 U of rHuPH20/g IgG, followed at the same site by IGSC doses equivalent to their previous IGIV dose and administration schedule. Subsequent IGSC dosing was adjusted based on IgG trough levels. An interim analysis of tolerability data was performed on a subset of 30 subjects. RESULTS:A total of 486 10% IGSC infusions, with or without rHuPH20, were all administered without interruption. Mean infusion volume every 4 weeks was 302 mL (30.2 g). The mean maximum infusion rate for a single site was 227 mL/h, and the mean time to infuse was 2.4hrs. Of the 30 patients analyzed, 29 reached their previous IV dosing interval, with the vast majority using a single site. Local adverse events (AEs) occurred in 16% of infusions. Most treatment-related AEs were mild and localized to the infusion site. The rate of all treatment-related systemic AEs was 8% of the infusions. CONCLUSION: The subcutaneous administration of 10% IGSC facilitated by rHuPH20 was well tolerated, at infusion intervals and rates comparable to the patient’s previous IGIV administration.