Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.

Allergy and Asthma Center Inc Toledo OH United States

Department of Clinical Immunology and Allergology St Anne's University Hospital in Brno Faculty of Medicine Masaryk University Brno Czechia

Department of Pediatric Allergy Asthma and Immunology University of Alabama Birmingham AL United States

Division of Basic and Clinical Immunology University of California Irvine Irvine CA United States

Division of Hematology Department of Medicine University of Alberta Hospital Edmonton AB Canada

Divisions of Adult and Pediatric Allergy and Immunology University of California San Diego La Jolla CA United States

IMMUNOe Research Center Centennial CO United States

Midlands Pediatrics Papillion NE United States

Octapharma Pharmazeutika Produktionsges m b H Vienna Austria

Pediatric Pulmonary Associates of North Texas Frisco TX United States

UCLA School of Medicine Los Angeles CA United States

Front Immunol. 2022 Dec 20;13:1110388. doi: 10.3389/fimmu.2022.1110388. PubMed

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Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. . International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. (2018) 38:96–128. 10.1007/s10875-017-0464-9 PubMed DOI PMC

Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. . International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. (2016) 4:38–59. 10.1016/j.jaip.2015.07.025 PubMed DOI PMC

The Immune Deficiency Foundation . Diagnostic & Clinical Care Guidelines for Primary Immunodeficiency Diseases. 3rd ed. Towson, MD: The immune deficiency Foundation.

Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. . Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. (2015) 136:1186–205 e1–78. 10.1016/j.jaci.2015.04.049 PubMed DOI

Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. (2008) 28:779–802. 10.1016/j.iac.2008.07.002 PubMed DOI

Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am. (2008) 28:413–37. 10.1016/j.iac.2008.01.008 PubMed DOI PMC

Krivan G, Jolles S, Granados EL, Paolantonacci P, Ouaja R, Cissé OA, et al. . New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients. Am J Clin Exp Immunol. (2017) 6:76–83. PubMed PMC

Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N. Home-based subcutaneous immunoglobulin vs. hospital-based intravenous immunoglobulin in treatment of primary antibody deficiencies:systematic review and meta analysis. J Clin Immunol. (2012) 32:1180–92. 10.1007/s10875-012-9720-1 PubMed DOI

Shapiro RS, Borte M. 7th International Immunoglobulin Conference:Immunoglobulin in clinical practice. Clin Exp Immunol. (2014) 178 (Suppl. 1):86. 10.1111/cei.12515 PubMed DOI PMC

Jolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, et al. . Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. (2015) 179:146–60. 10.1111/cei.12485 PubMed DOI PMC

Šedivá A, Chapel H, Gardulf A. The European Immunoglobulin Map Group (35 European Countries) for the European Society for Immunodeficiencies (ESID) Primary Immunodeficiencies Care in Development Working Party. Europe immunoglobulin map. Clin Exp Immunol. (2014) 178(Suppl. 1):141–3. 10.1111/cei.12546 PubMed DOI PMC

Compagno N, Malipiero G, Cinetto F, Agostini C. Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Front Immunol. (2014) 5:626. 10.3389/fimmu.2014.00626 PubMed DOI PMC

Gardulf A, Bjorvell H, Andersen V, Björkander J, Ericson D, Frøland SS, et al. . Lifelong treatment with gammaglobulin for primary antibody deficiencies:the patients' experiences of subcutaneous self-infusions and home therapy. J Adv Nurs. (1995) 21:917–27. 10.1046/j.1365-2648.1995.21050917.x PubMed DOI

Gardulf A, Andersen V, Bjorkander J, Ericson D, Frøland SS, Gustafson R, et al. . Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies:safety and costs. Lancet (1995) 345:365–9. 10.1016/S0140-6736(95)90346-1 PubMed DOI

Gardulf A, Nicolay U, Asensio O, Bernatowska E, Böck A, Carvalho BC, et al. . Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study. J Clin Immunol. (2006) 26:177–85. 10.1007/s10875-006-9002-x PubMed DOI

Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, et al. . Efficacy and safety of a new 20 immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. (2010) 30:734–45. 10.1007/s10875-010-9423-4 PubMed DOI PMC

Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, et al. . Efficacy and safety of Hizentra® in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. (2011) 141:90–102. 10.1016/j.clim.2011.06.002 PubMed DOI

Borte M, Bernatowska E, Ochs HD, Roifman CM, Vivaglobin Study G. Efficacy and safety of home-based subcutaneous immunoglobulin replacement therapy in paediatric patients with primary immunodeficiencies. Clin Exp Immunol. (2011) 164:357–64. 10.1111/j.1365-2249.2011.04376.x PubMed DOI PMC

Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, et al. . Efficacy and safety of hizentra(R), a new 20 immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. (2011) 31:752–61. 10.1007/s10875-011-9557-z PubMed DOI PMC

Borte M, Quinti I, Soresina A, Fernández-Cruz E, Ritchie B, Schmidt DS, et al. . Efficacy and safety of subcutaneous vivaglobin(R) replacement therapy in previously untreated patients with primary immunodeficiency:a prospective, multicenter study. J Clin Immunol. (2011) 31:952–61. 10.1007/s10875-011-9588-5 PubMed DOI

Jolles S, Borte M, Nelson RP, Jr, Rojavin M, Bexon M, Lawo JP, et al. . Long-term efficacy, safety, and tolerability of Hizentra(R) for treatment of primary immunodeficiency disease. Clin Immunol. (2014) 150:161–9. 10.1016/j.clim.2013.10.008 PubMed DOI

Borte M, Kriván G, Derfalvi B, Maródi L, Harrer T, Jolles S, et al. . Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20:a Phase 2/3 study in Europe in patients with primary immunodeficiencies. Clin Exp Immunol. (2017) 187:146–59. 10.1111/cei.12866 PubMed DOI PMC

Gardulf A, Moller G, Jonsson E. A comparison of the patient-borne costs of therapy with gamma globulin given at the hospital or at home. Int J Technol Assess Health Care (1995) 11:345–53. 10.1017/S0266462300006942 PubMed DOI

Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Subcutaneous Ig GSG. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. (2006) 26:265–73. 10.1007/s10875-006-9021-7 PubMed DOI

Wasserman RL, Melamed I, Kobrynski L, Strausbaugh SD, Stein MR, Sharkhawy M, et al. . Efficacy, safety, and pharmacokinetics of a 10 liquid immune globulin preparation (GAMMAGARD LIQUID, 10) administered subcutaneously in subjects with primary immunodeficiency disease. J Clin Immunol. (2011) 31:323–31. 10.1007/s10875-011-9512-z PubMed DOI

Lawo J-P, Hubsch A, Rojavin M. Quantification of the wear-off effect towards the end of the intravenous immunoglobulin infusion interval:pooled data analysis. J Allergy Clin Immunol. (2014) 133:AB179. 10.1016/j.jaci.2013.12.643 DOI

Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency:a meta-analysis of clinical studies. Clin Immunol. (2010) 137:21–30. 10.1016/j.clim.2010.06.012 PubMed DOI

Berger M. Choices in IgG replacement therapy for primary immune deficiency diseases:subcutaneous IgG vs. intravenous IgG and selecting an optimal dose. Curr Opin Allergy Clin Immunol. (2011) 11:532–8. 10.1097/ACI.0b013e32834c22da PubMed DOI

Rojavin MA, Hubsch A, Lawo JP. Quantitative evidence of wear-off effect at the end of the intravenous IgG (IVIG) dosing cycle in primary immunodeficiency. J Clin Immunol. (2016) 36:210–9. PubMed PMC

Wasserman RL, Irani AM, Tracy J, Tsoukas C, Stark D, Levy R, et al. . Pharmacokinetics and safety of subcutaneous immune globulin (human), 10 caprylate/chromatography purified in patients with primary immunodeficiency disease. Clin Exp Immunol. (2010) 161:518–26. 10.1111/j.1365-2249.2010.04195.x PubMed DOI PMC

Wasserman RL, Melamed I, Nelson RP, Knutsen AP, Fasano MB, Stein MR, et al. . Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. (2011) 50:405–14. 10.2165/11587030-000000000-00000 PubMed DOI

Debes A, Bauer M, Kremer S. Tolerability and safety of the intravenous immunoglobulin Octagam:a 10-year prospective observational study. Pharmacoepidemiol Drug Saf. (2007) 16:1038–47. 10.1002/pds.1449 PubMed DOI

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. (1999) 93:190–7. PubMed

Orange JS, Belohradsky BH, Berger M, Borte M, Hagan J, Jolles S, et al. . Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy. Clin Exp Immunol. (2012) 169:172–81. 10.1111/j.1365-2249.2012.04594.x PubMed DOI PMC

U.S. Department of Health and Human Services FaDA, and Center for Biologics Evaluation and Research. Guidance for Industry:Safety, Efficacy, and Pharmacokinetic Studies to Support Marketing of Immune Globulin Intravenous (human) as Replacement Therapy for Primary Humoral Immunodeficiency . Jun-2008. Available online at: http://www.gmp-compliance.org/guidemgr/files/IGIVIMMUNO.PDF

Octapharma Pharmazeutika Produktionsges . m.b.H. Cutaquig(R) (Immunoglobulin (Human) Subcutaneous 16.5 Solution for Injection). Canadian Product Monograph (2018).

CSL Behring . HIZENTRA, Immune Globulin Subcutaneous (Human), 20 Liquid. Canadian Product Monograph (2018).

Shire Pharma . CUVITRU, Normal Immune Globulin (Human), 20 Solution for Subcutaneous Infusion. Canadian Product Monograph (2018).

Suez D, Stein M, Gupta S, Hussain I, Melamed I, Paris K, et al. . Efficacy, Safety, and pharmacokinetics of a novel human immune globulin subcutaneous, 20 in patients with primary immunodeficiency diseases in North America. J Clin Immunol. (2016) 36:700–12. 10.1007/s10875-016-0327-9 PubMed DOI PMC

Burckbuchler V, Mekhloufi G, Giteau AP, Grossiord JL, Huille S, Agnely F. Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions. Eur J Pharm Biopharm. (2010) 76:351–6. 10.1016/j.ejpb.2010.08.002 PubMed DOI

Cilurzo F, Selmin F, Minghetti P, Adami M, Bertoni E, Lauria S, et al. . Injectability evaluation:an open issue. AAPS PharmSciTech. (2011) 12:604–9. 10.1208/s12249-011-9625-y PubMed DOI PMC

Haddad E, Berger M, Wang EC, Jones CA, Bexon M, Baggish JS. Higher doses of subcutaneous IgG reduce resource utilization in patients with primary immunodeficiency. J Clin Immunol. (2012) 32:281–9. 10.1007/s10875-011-9631-6 PubMed DOI PMC

Hernandez-Trujillo HS, Chapel H, Lo Re V, Notarangelo LD, Gathmann B, Grimbacher B, et al. . Comparison of American and European practices in the management of patients with primary immunodeficiencies. Clin Exp Immunol. (2012) 169:57–69. 10.1111/j.1365-2249.2012.04588.x PubMed DOI PMC

Ballow M, Wasserman RL, Jolles S, Chapel H, Berger M, Misbah SA. Assessment of local adverse reactions to subcutaneous immunoglobulin (SCIG) in clinical trials. J Clin Immunol. (2017) 37:517–8. 10.1007/s10875-017-0410-x PubMed DOI PMC

Long-term efficacy, safety, and tolerability of a subcutaneous immunoglobulin 16.5% (cutaquig®) in the treatment of patients with primary immunodeficiencies

A Multi‑Center, Open‑Label, Single‑Arm Trial to Evaluate the Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency

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ClinicalTrials.gov
NCT01888484