{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:36:21Z","timestamp":1780342581242,"version":"3.54.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1007\/s10875-018-0560-5","type":"journal-article","created":{"date-parts":[[2018,11,10]],"date-time":"2018-11-10T16:56:29Z","timestamp":1541868989000},"page":"864-875","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Long-Term Efficacy and Safety of Hizentra\u00ae in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-6804","authenticated-orcid":false,"given":"Stephen","family":"Jolles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail A.","family":"Rojavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Philip","family":"Lawo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Tortorici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kanegane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,10]]},"reference":[{"key":"560_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.iac.2008.01.008","volume":"28","author":"M Berger","year":"2008","unstructured":"Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin N Am. 2008;28:413\u201337.","journal-title":"Immunol Allergy Clin N Am"},{"key":"560_CR2","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/cei.12485","volume":"179","author":"S Jolles","year":"2015","unstructured":"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\u201360.","journal-title":"Clin Exp Immunol"},{"issue":"Suppl 1","key":"560_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1111\/cei.12555","volume":"178","author":"S Jolles","year":"2014","unstructured":"Jolles S, Jordan SC, Orange JS, van Schaik IN. Immunoglobulins: current understanding and future directions. Clin Exp Immunol. 2014;178(Suppl 1):163\u20138.","journal-title":"Clin Exp Immunol"},{"issue":"Suppl 1","key":"560_CR4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2249.2009.03954.x","volume":"157","author":"B Gathmann","year":"2009","unstructured":"Gathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008. Clin Exp Immunol. 2009;157(Suppl 1):3\u201311.","journal-title":"Clin Exp Immunol"},{"key":"560_CR5","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s10875-006-9021-7","volume":"26","author":"HD Ochs","year":"2006","unstructured":"Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26:265\u201373.","journal-title":"J Clin Immunol"},{"key":"560_CR6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1023\/A:1006678312925","volume":"20","author":"HM Chapel","year":"2000","unstructured":"Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20:94\u2013100.","journal-title":"J Clin Immunol"},{"key":"560_CR7","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.jaci.2004.06.053","volume":"114","author":"A Gardulf","year":"2004","unstructured":"Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Bock A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114:936\u201342.","journal-title":"J Allergy Clin Immunol"},{"key":"560_CR8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.2165\/11587030-000000000-00000","volume":"50","author":"RL Wasserman","year":"2011","unstructured":"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\u201314.","journal-title":"Clin Pharmacokinet"},{"key":"560_CR9","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s10875-016-0243-z","volume":"36","author":"MA Rojavin","year":"2016","unstructured":"Rojavin MA, Hubsch A, Lawo J-P. 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\u20139.","journal-title":"J Clin Immunol"},{"key":"560_CR10","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s10198-004-0250-5","volume":"6","author":"B H\u00f6gy","year":"2005","unstructured":"H\u00f6gy B, Keinecke H-O, Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance. Eur J Health Econ. 2005;6:24\u20139.","journal-title":"Eur J Health Econ"},{"key":"560_CR11","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1586\/1744666X.2014.957678","volume":"10","author":"RL Wasserman","year":"2014","unstructured":"Wasserman RL. Hizentra for the treatment of primary immunodeficiency. Expert Rev Clin Immunol. 2014;10:1293\u2013307.","journal-title":"Expert Rev Clin Immunol"},{"key":"560_CR12","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1007\/s10875-010-9423-4","volume":"30","author":"JB Hagan","year":"2010","unstructured":"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\u201345.","journal-title":"J Clin Immunol"},{"key":"560_CR13","doi-asserted-by":"crossref","unstructured":"Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, et al. Efficacy and safety of Hizentra\u00ae in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011;141:90\u2013102.","DOI":"10.1016\/j.clim.2011.06.002"},{"key":"560_CR14","doi-asserted-by":"crossref","unstructured":"Jolles S, Borte M, Nelson RP Jr, Rojavin M, Bexon M, Lawo J-P, et al. Long-term efficacy, safety, and tolerability of Hizentra\u00ae for treatment of primary immunodeficiency disease. Clin Immunol. 2014;150:161\u20139.","DOI":"10.1016\/j.clim.2013.10.008"},{"key":"560_CR15","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1007\/s10875-013-9985-z","volume":"34","author":"H Kanegane","year":"2014","unstructured":"Kanegane H, Imai K, Yamada M, Takada H, Ariga T, Bexon M, et al. Efficacy and safety of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency diseases. J Clin Immunol. 2014;34:204\u201311.","journal-title":"J Clin Immunol"},{"key":"560_CR16","doi-asserted-by":"publisher","first-page":"AB181","DOI":"10.1016\/j.jaci.2013.12.649","volume":"133","author":"JS Sidhu","year":"2014","unstructured":"Sidhu JS, Rojavin M, Berger M, Bexton M, Edelman JM. Pharmacokinetic modeling predicts different IgG exposures using different IVIG-SCIG dose conversion factors in patients with primary immune deficiency. J Allergy Clin Immunol. 2014;133:AB181.","journal-title":"J Allergy Clin Immunol"},{"key":"560_CR17","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3389\/fimmu.2014.00629","volume":"5","author":"J Kerr","year":"2014","unstructured":"Kerr J, Quinti I, Eibl M, Chapel H, Sp\u00e4th PJ, Sewell WAC, et al. Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in Europe. Front Immunol. 2014;5:629.","journal-title":"Front Immunol"},{"key":"560_CR18","unstructured":"FDA. Guidance for industry: safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. Available from: \n                    http:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/GuidanceComplianceRegulatoryInformation\/Guidances\/Blood\/ucm078526.pdf\n                    \n                  . Accessed 6 Nov 2018."},{"key":"560_CR19","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3810\/pgm.2013.11.2712","volume":"125","author":"C Landersdorfer","year":"2013","unstructured":"Landersdorfer C, Bexon M, Edelman J, Rojavin M, Kirkpatrick C, Lu J, et al. Pharmacokinetic modeling and simulation of biweekly subcutaneous immunoglobulin dosing in primary immunodeficiency. Postgrad Med. 2013;125:53\u201361.","journal-title":"Postgrad Med"},{"key":"560_CR20","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1002\/sim.1405","volume":"22","author":"PL Graham","year":"2003","unstructured":"Graham PL, Mengersen K, Morton AP. Confidence limits for the ratio of two rates based on likelihood scores: non-iterative method. Stat Med. 2003;22:2071\u201383.","journal-title":"Stat Med"},{"key":"560_CR21","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1182\/blood-2003-06-1964","volume":"103","author":"H Takada","year":"2003","unstructured":"Takada H, Kanegane H, Nomura A, Yamamoto K, Ihara K, Takahashi Y, et al. Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. Blood. 2003;103:185\u20137.","journal-title":"Blood"},{"key":"560_CR22","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s13554-014-0018-0","volume":"4","author":"J Sidhu","year":"2014","unstructured":"Sidhu J, Rojavin MA, Pfister M, Edelman J. Enhancing patient flexibility of subcutaneous immunoglobulin G dosing: pharmacokinetic outcomes of various maintenance and loading regimens in the treatment of primary immunodeficiency. Biol Ther. 2014;4:41\u201355.","journal-title":"Biol Ther"},{"key":"560_CR23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s40261-015-0270-1","volume":"35","author":"A Vultaggio","year":"2015","unstructured":"Vultaggio A, Azzari C, Milito C, Finocchi A, Toppino C, Spadaro G, et al. Subcutaneous immunoglobulin replacement therapy in patients with primary immunodeficiency in routine clinical practice: the VISPO prospective multicenter study. Clin Drug Investig. 2015;35:179\u201385.","journal-title":"Clin Drug Investig"},{"key":"560_CR24","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s10875-008-9231-2","volume":"29","author":"MR Stein","year":"2009","unstructured":"Stein MR, Nelson RP, Church JA, Wasserman RL, Borte M, Vermylen C, et al. Safety and efficacy of Privigen\u00ae, a novel 10% liquid immunoglobulin preparation for intravenous use, in patients with primary immunodeficiencies. J Clin Immunol. 2009;29:137\u201344.","journal-title":"J Clin Immunol"},{"key":"560_CR25","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.jaci.2010.02.040","volume":"125","author":"M Lucas","year":"2010","unstructured":"Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125:1354\u201360.","journal-title":"J Allergy Clin Immunol"},{"key":"560_CR26","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s10875-011-9511-0","volume":"31","author":"I Quinti","year":"2011","unstructured":"Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31:315\u201322.","journal-title":"J Clin Immunol"},{"key":"560_CR27","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jaip.2013.09.015","volume":"1","author":"S Jolles","year":"2013","unstructured":"Jolles S. The variable in common variable immunodeficiency: a disease of complex phenotypes. J Allergy Clin Immunol Pract. 2013;1:545\u201356 quiz 557.","journal-title":"J Allergy Clin Immunol Pract"},{"key":"560_CR28","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/cei.12866","volume":"187","author":"M Borte","year":"2017","unstructured":"Borte M, Krivan G, Derfalvi B, Marodi 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\u201359.","journal-title":"Clin Exp Immunol"},{"key":"560_CR29","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1007\/s10875-011-9557-z","volume":"31","author":"M Borte","year":"2011","unstructured":"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\u201361.","journal-title":"J Clin Immunol"},{"key":"560_CR30","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/j.1365-2249.2010.04195.x","volume":"161","author":"RL Wasserman","year":"2010","unstructured":"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\u201326.","journal-title":"Clin Exp Immunol"},{"key":"560_CR31","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1023\/B:JOCI.0000029108.18995.61","volume":"24","author":"M Berger","year":"2004","unstructured":"Berger M, Pinciaro PJ, Flebogamma I. Safety, efficacy, and pharmacokinetics of Flebogamma 5% [immune globulin intravenous (human)] for replacement therapy in primary immunodeficiency diseases. J Clin Immunol. 2004;24:389\u201396.","journal-title":"J Clin Immunol"},{"key":"560_CR32","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1007\/s10875-006-9025-3","volume":"26","author":"JA Church","year":"2006","unstructured":"Church JA, Leibl H, Stein MR, Melamed IR, Rubinstein A, Schneider LC, et al. Efficacy, safety and tolerability of a new 10% liquid intravenous immune globulin [IGIV 10%] in patients with primary immunodeficiency. J Clin Immunol. 2006;26:388\u201395.","journal-title":"J Clin Immunol"},{"key":"560_CR33","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s10875-012-9656-5","volume":"32","author":"RL Wasserman","year":"2012","unstructured":"Wasserman RL, Church JA, Stein M, Moy J, White M, Strausbaugh S, et al. Safety, efficacy and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeficiency. J Clin Immunol. 2012;32:663\u20139.","journal-title":"J Clin Immunol"},{"key":"560_CR34","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s10875-011-9512-z","volume":"31","author":"RL Wasserman","year":"2011","unstructured":"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\u201331.","journal-title":"J Clin Immunol"},{"key":"560_CR35","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s10875-006-9002-x","volume":"26","author":"A Gardulf","year":"2006","unstructured":"Gardulf A, Nicolay U, Asensio O, Bernatowska E, B\u00f6ck A, Carvalho BC, et al. Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies\u2014a prospective, multi-national study. J Clin Immunol. 2006;26:177\u201385.","journal-title":"J Clin Immunol"},{"key":"560_CR36","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/cei.12866","volume":"187","author":"M Borte","year":"2016","unstructured":"Borte M, Kriv\u00e1n G, Derfalvi B, Mar\u00f3di 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. 2016;187:146\u201359.","journal-title":"Clin Exp Immunol"},{"key":"560_CR37","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1007\/s10875-016-0327-9","volume":"36","author":"D Suez","year":"2016","unstructured":"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\u201312.","journal-title":"J Clin Immunol"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10875-018-0560-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-018-0560-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-018-0560-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T21:04:24Z","timestamp":1581973464000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10875-018-0560-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["560"],"URL":"https:\/\/doi.org\/10.1007\/s10875-018-0560-5","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"6 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients prior to inclusion in the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"Stephen Jolles has participated in advisory boards, trials, projects, and has been a speaker with Baxalta, CSL Behring, Shire, Thermofisher, Swedish Orphan Biovitrum, Biotest, Binding Site, Grifols, BPL, Octapharma, LFB, GSK, Weatherden, Zarodex, Sanofi, and UCB Pharma. Mikhail Rojavin, John-Philip Lawo, and Michael A. Tortorici are employees of CSL Behring. Robert Nelson Jr. reported no conflicts of interest. Richard L. Wasserman has been Consultant and Investigator for BPL, Korean Green Cross, Prometic, Therapure, and Shire, and has been a speaker for Shire. Michael Borte has no potential conflicts of interest. Kohsuke Imai has been a Consultant for CSL Behring, a Speaker for CSL Behring, Novartis, The Japan Blood Products Organization. Hirokazu Kanegane has received research grant support from CSL Behring and the Japanese Blood Products Organization, and has been a Consultant for CSL Behring.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}