Journal of Clinical Immunology, Vol. 26, No. 3, May 2006 ( C  2006) DOI: 10.1007/s10875-006-9021-7 Safety and Efficacy of Self-Administered Subcutaneous Immunoglobulin in Patients with Primary Immunodeficiency Diseases HANS D. OCHS, 1,6 SUDHIR GUPTA, 2 PETER KIESSLING, 3 UWE NICOLAY, 4 MELVIN BERGER, 5 and the Subcutaneous IgG Study Group Received March 2, 2006; accepted March 31, 2006 Published online: 2 June 2006 Intravenous immunoglobulin (IVIg) infusions at 3–4 week in- tervals are currently standard therapy in the United States for patients with primary immune deficiency diseases (PIDD). To evaluate alternative modes of immunoglobulin administration we have designed an open-label study to investigate the efficacy and safety of a subcutaneously administered immunoglobulin preparation (16% IgG) in patients with PIDD. After their final IVIg infusion, 65 patients entered a 3-month, wash-in/wash-out phase, designed to bring patients to steady-state with subcuta- neously administered immunoglobulin. This was followed by 12 months of weekly SCIg infusions, at a dose determined in a pharmacokinetic substudy to provide noninferior intravascular exposure. This resulted in a mean weekly dose of 158 mg/kg, calculated to equal 137% of the previous intravenous dose. Two patients (4%) each reported 1 serious bacterial infection (pneumonia), an annual rate of 0.04 per patient-year. There were 4.43 infections of any type per patient-year. Mean trough serum IgG levels increased from 786 to 1040 mg/dL during the study, a mean increase of 39%. The most frequent treatment- related adverse event was infusion-site reaction, reported by 91% of patients; this was predominantly mild or moderate, and the incidence decreased over time. No treatment-related serious adverse events were reported. We conclude that subcutaneous 1 University of Washington School of Medicine, Department of Pedi- atrics, Seattle, Washington. 2 Department of Medicine, University of California, Division of Basic & Clinical Immunology, Irvine, California. 3 ZLB Behring, Marburg, Germany. 4 Karolinska Institutet, Sweden. 5 Rainbow Babies and Children’s Hospital, Division of Allergy, Im- munology and Rheumatology, Cleveland, Ohio. 6 To whom correspondence should be addressed to Department of Pediatrics, University of Washington School of Medicine, 307 Westlake Avenue North, Suite 300, Seattle, Washington, 98109; e-mail: allgau@u.washington.edu. administration of 16% SCIg is a safe and effective alternative to IVIg for replacement therapy of PIDD. KEY WORDS: Primary immune deficiency diseases; immunoglobulin therapy; subcutaneous; intravenous; safety and efficacy. INTRODUCTION Immunoglobulin replacement has been standard ther- apy for patients with primary immune deficiency diseases (PIDD) since it was introduced more than 50 years ago by Bruton and colleagues to treat a patient with agam- maglobulinemia (1). Long-term treatment, using human immunoglobulin derived from donated plasma, reduces the frequency and severity of infections by maintaining serum immunoglobulin G (IgG) concentrations closer to physiological levels in the normal population. Although Bruton initially administered immunoglobulin subcuta- neously, intravenous administration became the preferred mode of administration in the 1980s. Intravenously ad- ministered immunoglobulin (IVIg) allowed infusion of higher doses over a relatively short time, and has remained the standard route of administration in much of the world. However, IVIg therapy is not ideal for all patients and may be difficult for those with poor venous access or those experiencing recurrent systemic reactions. Reactions to IVIg therapy that persist beyond the first infusion are usu- ally mild to moderate and include myalgia, fever, chills, Abbreviations used: AEs: adverse events; CL: confidence limit; HIV: hu- man immunodeficiency virus; ITT: intention-to-treat; IgA: immunoglob- ulin A; IgG: immunoglobulin G; PIDD: primary immune deficiency diseases; IVIg: intravenously administered immunoglobulin; SCIg: sub- cutaneously administered immunoglobulin; SBIs: serious bacterial in- fections. 265 0271-9142/06/0500-0265/0 C  2006 Springer Science+Business Media, Inc.