Subcutaneous IgG Research Articles

Subcutaneous IgG Replacement Therapy by Push in 32 Patients with Primary Immunodeficiency Diseases in Argentine

Introduction: Regular replacement with immunoglobulin infusions is the mainstay of treatment in the majority of primary immunodeficiencies. Several studies showed that Subcutaneous Immunoglobulin (SCIG) has similar efficacy to Intravenous Immunoglobulin (IVIG) in preventing infections in PID patients. Here we report effectiveness, safety and tolerance of SCIG replacement therapy by push in 32 pediatric and adult patients with humoral PID in Argentina. Results: We describe 32 patients that received SCIG treatment between July 2011 and May 2012. 17 male and 15 female from 2 Immunology Centers; aged from 8 months to 40 years (median: 11 years). 30 patients previously received IVIG treatment. Among them, fifteen received 9 months of SCIG treatment administered by pump. The other 2 patients started the immunoglobulin replacement treatment directly with SCIG by push. The mean dose of SCIG was 133 mg/kg/week (range 100-192). The annual rate of any infection was 1, 2 infection/year/patient for subcutaneous treatment. The frequency of adverse effects was 0.02% with the SCIG. At the end of the study, all patients chose SCIG home-therapy regimen and referred much more comfort with SCIG by push. Conclusion: Self-administered subcutaneous immunoglobulin therapy by push is an effective and safe alternative therapy for patients with PID.

Subcutaneous IgG in neurologic diseases

Subcutaneous administration of IgG (SCIG) has become widely used in primary immune deficiency diseases but it has only recently been studied for maintenance therapy in autoimmune peripheral neuropathies, such as chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy. Weekly self-administration of SCIG is safe and well-tolerated, and results in steady-state serum IgG levels, as contrasted with the peaks and troughs of monthly immune globulin (human) for intravenous use. Freedom from the need for venous access or medical personnel for infusions, flexibility in scheduling, convenience of home therapy, and improved clinical stability due to the steady-state IgG levels, lead many patients to prefer SCIG to immune globulin (human) for intravenous use. Long-term studies are needed to determine if the constant IgG levels and clinical stability translate into better long-term outcomes.

Pharmacokinetic Modeling and Simulation of Biweekly Subcutaneous Immunoglobulin Dosing in Primary Immunodeficiency

Replacement therapy with immunoglobulin G (IgG) given as intravenous or subcutaneous (SC) infusions is the standard treatment for patients with primary immunodeficiency. Due to the life-long need for replacement, increased flexibility in the administration and dosage regimens would improve patients' quality of life. A population pharmacokinetic model that can predict plasma IgG concentrations for various routes, dosage regimens, and patient groups is a valuable tool to improve patient therapy. Such a model was developed based on IgG concentrations from 151 unique adult and pediatric patients who participated in 4 clinical trials of intravenous and SC IgG replacement therapy. Simulations predicted that the same total IgG dose, delivered SC, either in 1 biweekly dose (once every 2 weeks), or in 2 weekly doses, results in IgG peak and trough concentrations that remain within ± 10% of each other throughout the 14-day period. The developed population pharmacokinetic model predicted that biweekly SC Hizentra dosing offers a viable alternative to weekly SC therapy, allowing more flexible and optimized dosage regimens for patients with primary immunodeficiency.

Adverse Effects of IgG Therapy

IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered.

Comparative Study of Subcutaneous Versus Intravenous IgG Replacement Therapy in Pediatric Patients with Primary Immunodeficiency Diseases: A Multicenter Study in Argentina

Several studies have shown that subcutaneous immunoglobulin (SCIG) infusions demonstrate similar efficacy to intravenous Ig (IVIG) in preventing infections in patients with primary immunodeficiency diseases (PID), and are safe and well tolerated in this population. This open, prospective/retrospective, multicenter study was designed to compare the effectiveness, safety and tolerability of a 16% liquid human IgG preparation (Beriglobina P), administered SC, with previous IVIG treatment in PID pediatric patients in Argentina. Fifteen subjects were enrolled in the study, and a total of 13 subjects (aged 6-18years) completed the 36-week SCIG treatment period. All children had previously received IVIG treatment. The dose of SCIG equaled the previous IVIG dose and subjects received an average weekly dose of 139mg/kg (range 105-181) during the SCIG period. Significantly higher serum IgG trough levels were recorded on SCIG treatment at 16, 24, and 36weeks, when compared with previous IgG trough levels on steady-state IVIG treatment. The annualized infection rate was 1.4 infections/subject/year during the IVIG administration period compared with 0.4 infections/subject/year during the SCIG period. All subjects who completed the study chose to continue administering SCIG at home after the study had ended. These data confirm that self-administered SCIG therapy is a well-tolerated and effective alternative to IVIG therapy for children with PID.

Immune Globulin (Human) 10 % Liquid: A Review of its Use in Primary Immunodeficiency Disorders

Human immune globulin (IG) 10 % liquid (Gammagard Liquid®) is a ready-to-use, highly purified, and concentrated immunoglobulin (Ig)G solution approved in the US for both intravenous and subcutaneous antibody replacement therapy in patients aged ≥ 2 years with primary humoral immunodeficiency. Intravenous IG 10 % liquid every 3-4 weeks for ≥ 12 months, at median serum IgG trough levels of 9.6-11.2 g/L, completely prevented acute serious bacterial infections (SBIs) in a phase III clinical trial. Weekly subcutaneous IG 10 % liquid at a dose equal to 137 % of the equivalent weekly intravenous dose, which was earlier determined to produce the same IgG exposure, produced higher serum trough IgG levels and lower peak IgG levels than intravenous administration, and also effectively reduced SBIs; the infection rate was 0.067 SBIs/subject/year, which met the US FDA efficacy criterion of < 1 SBI/subject/year. The rates for non-serious infections of any kind were low for both intravenous and subcutaneous therapy. Both intravenous and subcutaneous IG 10 % liquid were safe and generally well tolerated. Systemic adverse reactions were more frequent with intravenous therapy and local infusion-site reactions were more frequent with subcutaneous therapy, but the latter reduced over time. Most adverse reactions were of mild or moderate intensity. Thus, IG 10 % liquid is an effective and generally well-tolerated preparation for both intravenous and subcutaneous IgG replacement therapy in patients with primary immunodeficiency disorders involving antibody deficiency. It offers the benefits of a ready-to-use, liquid preparation and the convenience of home-based therapy in appropriate patients.

Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients

Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG.

Bioavailability of IgG Administered by the Subcutaneous Route

PurposeUS licensing studies of subcutaneous IgG (SCIG) calculate dose adjustments necessary to achieve area under the curve (AUC) of serum IgG vs. time on SCIG that is non-inferior to that on intravenous IgG (IVIG), within the FDA-set limit of ±20 %. The results are interpreted as showing that different SCIGs differ in bioavailability. We used three approaches to determine if the bioavailabilities were actually different.MethodsDose adjustments and AUCs from published licensing studies were used to calculate bioavailabilities using the formula: Bioavailability (% of IVIG) = AUC(SCIG) ÷ AUC(IVIG) x 1/Dose Adjustment. We also compared the increment in serum IgG concentration achieved with varying doses of SCIG in recent meta-analyses with the increment with different doses of IVIG, and determined the serum IgG concentrations when patients switched SCIG products at the same dose.ResultsThe actual bioavailabilities were: Gamunex® 65.0 %, Hizentra® 65.5 %, Gammagard® 67.2 %, Vivaglobin® 69.0 %. Regression analyses of serum IgG vs. dose showed that the mean increase in serum IgG resulting from a 100 mg/kg/month increment in SCIG dosing was 69.4 % of the increase with the same increment in IVIG dosing (84 mg/dL vs. 121 mg/dL). Patients switching SCIG preparations at the same dose had no change in serum IgG levels, confirming that bioavailabilities of the SCIG preparations did not differ.ConclusionsDecreased bioavailability appears to be a basic property of SCIG and not a result of any manufacturing process or concentration. Because serum IgG levels do not vary with different SCIG products at the same dose, adjustments are not necessary when switching products.

Variability in Intravenous Immunoglobulin G Regimens for Autoimmune Neuromuscular Disorders

Aims: We reviewed the intravenous immunoglobulin G (IVIG) dispensing records of a specialty pharmacy to characterize the IVIG treatment regimens used for chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) in community practice. Methods: Anonymized records were selected based on International Classification of Diseases, Ninth Revision (ICD-9) codes and IVIG treatment for > 1 month. Each patient's immunoglobulin G (IgG) dose per infusion (mg/kg/dose) was multiplied by the number of doses per month (30.5 days divided by the dosing interval in days) to yield the total monthly dose (mg/kg/month). Data were analyzed and summarized using descriptive statistics. Results: Forty-six patients (median age, 56.5 years; range, 8−86 years) fulfilled the inclusion criteria. Thirty-one patients with CIDP received IgG at 7- to 92-day intervals (mean [standard deviation (SD)], 28 [16] days). The mean (SD) IgG dose was 75 (60) g/dose, equivalent to 866 (623) mg/kg/dose and 1145 (778) mg/kg/month. Six patients with stable MG received IVIG or subcutaneous IgG at 3.5- to 61-day intervals (28 [20] days) at a mean (SD) IgG dose of 39 (15) g/dose, equivalent to 405 (108) mg/kg/dose and 783 (680) mg/kg/month. Nine patients with MG with acute exacerbations received IgG at 7- to 42-day intervals (22 [12] days) at a mean (SD) dose of 40 (21) g/dose, equivalent to 403 (172) mg/kg/dose and 641 (288) mg/kg/month. One patient with CIDP and 4 patients with MG were treated with weekly subcutaneous IgG injections. Conclusion: Although patients with CIDP and MG are treated with mean total monthly IgG doses similar to those approved by the US Food and Drug Administration, the individual doses and intervals vary considerably, suggesting that physicians may be adjusting IgG dosing according to each patient's clinical condition and treatment response. Further study is necessary to determine the criteria used to adjust IgG treatment regimens and whether these adjustments optimize clinical outcomes while limiting overall costs.

Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein

IntroductionThe conversion from intravenous (IV) to subcutaneous (SC) delivery of biotherapeutics has increased in recent years. Some of the reasons for this shift in route of delivery are due to patient convenience, reduced adverse systemic effects, lack of a need for vascular access, and reduced cost of patient care, which ultimately lead to improved patient quality of life. One caveat to SC delivery is the limited volumes that can be administered at a single site and the associated local tolerability. To characterize factors that affect subcutaneous delivery of large volumes of therapeutic proteins, a porcine model was developed. Model endpoints included measurement of interstitial pressure, assessment of local skin visco-elasticity, and the qualitative assessment of local infusion sites. MethodsImmunoglobulin G (IgG) was subcutaneously infused into the abdominal region of Yucatan miniature swine. Changes in interstitial pressure were measured, using an in-line pressure transducer, during and after infusions. Additionally, pre- and post-infusion changes in local skin visco-elasticity were measured using a Cutometer®. Lastly, infusion sites were assessed for post-infusion local skin reactions such as erythema and swelling. Similar assessments were made following SC IgG delivery with the permeation enhancer recombinant human hyaluronidase PH20 (rHuPH20). ResultsSubcutaneous infusions of IgG, in the presence of rHuPH20, significantly reduced average interstitial pressures by 55% during the infusion period and by 67% during the post-infusion period, compared to the control. Infusions in the presence of rHuPH20 also maintained better local skin elasticity as seen by a 42% increase in local skin pliability compared to the control. Finally, infusions with rHuPH20 resulted in an 80% reduction in swelling area compared to the control. DiscussionA large animal model was developed that incorporates both quantitative and qualitative assessment methods to aid in understanding SC delivery of proteins.

Clinical Ambiguities—Ongoing Questions

Many factors need to be considered when choosing the mode of delivery of immunoglobulin (IgG) replacement therapy for a given patient with primary immunodeficiency disease (PIDD). Despite some general guidance as provided in the previous discussions, a number of ongoing questions remain. This article attempts to provide some answers and clarification for clinical situations in which the choice of intravenous IgG (IVIG) or subcutaneous IgG (SCIG) may be ambiguous.

Overview of Routes of IgG Administration

The use of exogenous serum to provide protection against infections began more than a century ago. Over time, this concept matured and led to the preparation of concentrated immunoglobulin (IgG) products that were safe and effective when delivered subcutaneously (SC) or intramuscularly (IM) but were not ideal for intravenous (IV) use. Continued improvements led to the development of IgG preparations that are safe for either subcutaneous IgG (SCIG) or intravenous IgG (IVIG) delivery and allow providers and patients significant flexibility to develop an effective but manageable treatment plan. Factors that influence the choice of IgG product and delivery method can maximize the therapeutic benefit and provide the best possible quality of life for patients.

Subcutaneous IgG replacement after pediatric SCT

Hypogammaglobulinemia is common after pediatric SCT and IgG replacement is recommended. Some children will have a prolonged hypogammaglobulinemia but may have poor venous access which impedes further iv IgG replacement. In primary antibody deficiencies, sc IgG replacement, performed by parents at home, has been shown to be efficient and to improve life quality. In this study prolonged hypogammaglobulinemia post-SCT was observed in 58 of 158 (37%) children transplanted 2003-2010. Iv IgG (n = 46) and sc IgG (n = 12) replacement was compared and in 32 of 35 surviving children, it was possible to assess family attitudes to the treatment. There was no significant difference in numbers of patients reaching IgG ≥4 g/L (64-96%) or IgG trough levels between the two groups. However, the levels were less variable in the sc IgG group. Side effects associated with the IgG replacement occurred more frequently in the iv IgG group (67.4% vs. 16.7%, p = 0.003). The frequency of clinical infections was equal in the groups. No family in the sc IgG group desired change of route of administration in contrast to the iv IgG group. To conclude, sc IgG replacement is a convenient and safe alternative to iv IgG replacement which should be offered to children undergoing SCT.

A Randomised, Double-Blinded, Placebo Controlled Trial of the Effect of Subcutaneous Immunoglobulin on Muscular Performance in Chronic Inflammatory Demyelinating Polyneuropathy (P06.130)

Objective: We hypothesised that the effect of subcutaneous infusion of immunoglobulins(SCIG) on muscular performance in chronic inflammatory demyelinating polyneuropathy(CIDP) is superior to that of placebo and equals the therapeutic effect of intravenous infusion(IVIG). Background Subcutaneous treatment with large amounts of immunoglobulins in multifocal motor neuropathy is feasible, safe and effective. In CIDP case reports indicate its therapeutic usefullness as well. Design/Methods: Subjects in IVIG maintenace therapy full-filling the EFNS/PNS criteria for CIDP were considered for participation. Exclusion criteria were pregnancy, malignancies, dementia, severe medical disorders and psychiatric disturbances. Thirty CIDP patients(n,30) characterized as IVIG-responders by their treating physicians were included in the study.Participants were randomised to receive either subcutaneous IgG at a concentration of 1.6g/10cc or subcutaneous saline in a double-blinded fashion. Infusions were given twice or thrice weekly for 12 weeks at home. The amount of immunoglobulin corresponded to the clinically predetermined dose. The first subcutaneous infusion was delivered two weeks after the last IVIG treatment. Participants were evaluated at four time intervals: - 2 wks, 0, 10 wks, 12 wks. Strength was determined at isokinetic dynamometry from four predetermined and weakened muscle groups. Also, an Overall Disability Sum Score (ODSS), a 40 meter walking test, a nine hole peg test, a Neurological Impairment Score (NIS), a Medical Research Council (MRC) score and a grip strength test were included. The primary end-point is the change of strength at isokinetic dynamometry in the two study groups. Secondary end-points are the treatment response of SCIG vs IVIG and the variation of the treatment response during SCIG vs IVIG. Results: The study ran during the period april 2010 to october 2011. Data will be presented. Conclusions: To be presented. Supported by: Aarhus University Hospital. A research grant from Baxter. Disclosure: Dr. Jakobsen has received research support from Baxter Medical AB. Dr. Markvardsen has nothing to disclose. Dr. Harbo has nothing to disclose. Dr. Sindrup has received personal compensation for activities with Grunenthal, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly & Company, and Pfizer Inc. Dr. Andersen has nothing to disclose. Dr. Christiansen has nothing to disclose. Dr. Olsen has nothing to disclose. Dr. Lassen has nothing to disclose.

Subcutaneous Hizentra® (20%) Is Better Tolerated And Shares Similar Efficacy Compared To Subcutaneous Vivaglobin® (16%)

Replacement Subcutaneous IgG (SCIG) therapy is effective treatment in reducing rates of infections in patients with primary immunodeficiency diseases (PIDD), but there are few comparative studies using different SCIG preparations. This study examines the tolerability and efficacy of Hizentra (20%) subcutaneous immune globulin (SCIG) product compared to Vivaglobin (16%). A prospective, single-center, open-label cohort of 32 PIDD subjects, who received 16% Vivaglobin for at least 6 months and transitioned to 20% Hizentra for 24 weeks. Number of acute serious bacterial infections (aSBI) and overall tolerability on Vivaglobin was assessed for 8 weeks prior to switch and compared to Hizentra over 24 weeks. Average Hizentra dose was higher than Vivaglobin at 161.6 +/- 99.8 and 145.9 +/- 88.2 mg/kg/week, respectively (p < 0.0001). The study is ongoing and preliminary findings for all subjects through 12 weeks on Hizentra are reported. aSBI/subject/year while receiving Vivaglobin was 0.2 compared to 0.14 on Hizentra. Per-person annual rates of other infections were lower for Vivaglobin at 1.2 versus 2.63 for Hizentra (p = 0.0167). There were no infusion-related serious adverse events in either group. Average infusion time decreased from 108 minutes (3.2 sites) with Vivaglobin to 72 minutes (2.1 sites) with Hizentra. Mean Vivaglobin IgG were similar to Hizentra, 1096.1 (+/- 231.2) and 1105.2 (+/- 233.3) mg/dL, respectively (p = 0.77). Both groups had similar titers to varicella (103.1 versus 107.9 EU/mL) and tetanus (2.8 versus 2.9 IU/mL) on Vivaglobin and Hizentra, respectively. Hizentra (20%) achieves better tolerability and similar efficacy to Vivaglobin (16%).

Higher doses of subcutaneous IgG reduce resource utilization in patients with primary immunodeficiency.

The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses.

Choices in IgG replacement therapy for primary immune deficiency diseases

Subcutaneous IgG (SCIG) is becoming more popular, but there is still uncertainty about efficacy and optimal dosing. This review discusses recent pharmacokinetic studies and applications of SCIG therapy, and its efficacy in the context of emerging understanding of the relationship between dosing and efficacy of both intravenous IgG (IVIG) and SCIG replacement therapy for primary immunodeficiency diseases. Three preparations of IgG have been licensed in the US in the past year. Their bioavailabilities are 65-70% of that of IVIG. Pooled analyses show that the efficacy of SCIG in preventing infections is proportional to the steady-state levels achieved, and similar to that of IVIG. Pharmacokinetic studies allow estimation of doses that will yield desired serum levels with both IVIG and SCIG, and when switching from one route to another. Pooled analyses show that at equivalent total doses, weekly SCIG results in steady-state levels 10-20% higher than troughs on monthly IVIG. For most patients, the choice between routes should be based on individual preference, and the regimen should be individualized to achieve the desired outcomes.

Efficacy and Safety of Subcutaneous Vivaglobin® Replacement Therapy in Previously Untreated Patients with Primary Immunodeficiency: A Prospective, Multicenter Study

Treatment of primary immunodeficiency (PI) is typically initiated with intravenous immunoglobulin (IVIG) loading and then continued with IVIG or subcutaneous IgG (SCIG). This prospective, open-label, multicenter, 6-month study evaluated a new regimen of initiating IgG therapy with SCIG in 18 previously untreated patients. In the loading phase, SCIG 100 mg/kg was administered for five consecutive days (total loading dose 500 mg/kg). During the maintenance phase, patients self-infused SCIG 100 mg/kg/week at home. The primary efficacy endpoint of IgG levels ≥5 g/L on day 12 was achieved in 17 patients (94.4%; 95% CI 0.727, 0.999). The rate of infections was 3.95 episodes/patient/year. Improvement was found in many subscales of the health-related quality of life questionnaires. SCIG treatment was well tolerated, with no related serious adverse events (AEs). Nine (50%) patients experienced related AEs, including local reactions (rate 0.105 events/infusion). The results suggest that therapy of newly diagnosed patients with PI can be initiated directly with SCIG.

Efficacy and Safety of Hizentra®, a New 20% Immunoglobulin Preparation for Subcutaneous Administration, in Pediatric Patients with Primary Immunodeficiency

Subcutaneous IgG treatment for primary immunodeficiencies (PI) is particularly well suited for children because it does not require venous access and is mostly free of systemic adverse events (AEs). In a prospective, open-label, multicenter, single-arm, Phase III study, 18 children and five adolescents with PI were switched from previous intravenous (IVIG) or subcutaneous (SCIG) IgG treatment to receive dose-equivalent, weekly subcutaneous infusions of Hizentra® for 40 weeks. Mean IgG trough levels were maintained in patients previously on SCIG, or increased in those previously on IVIG, regardless of age. No serious bacterial infections were reported during the efficacy period of the study. The rates of non-serious infections were 4.77 (children) and 5.18 (adolescents) infections per patient per year. Related AEs were observed in seven children (38.9%) and two adolescents (40%). Three serious AEs and two AEs leading to discontinuation (all unrelated) were reported in children. Hizentra® is an effective and well-tolerated treatment for pediatric patients.

Efficacy and safety of Hizentra® in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra(®), a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra(®) at doses equivalent to their previous treatment. IgG levels achieved with Hizentra(®) were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra(®)-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra(®) maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.