Subcutaneous Immune Globulin Research Articles

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%).

Patients with primary immunodeficiency receiving subcutaneous immune globulin Hizentra maintain health-related quality of life and treatment satisfaction in a multicentre extension study of efficacy, tolerability and safety

Objective The purpose of the study was to evaluate the maintenance and sustainability of health-related quality of life (HRQoL) in patients being treated long-term for primary immunodeficiency (PID) with subcutaneous infusions of Hizentra, a new human immunoglobulin G containing proline. Methods Twenty-one patients who completed a 12-month Phase III open-label, single-arm, prospective, multicentre study of the efficacy, tolerability, safety and pharmacokinetics of Hizentra were offered the opportunity to participate in an extension phase. HRQoL and treatment satisfaction were measured every 12–60 weeks using the Medical Outcomes Study Short-Form 36 (SF-36v2), EuroQol 5D (EQ-5D) Index Score, Life Quality Index (LQI), Treatment Satisfaction Questionnaire for Medication Short Form (TSQMv1.4), and a disease-specific Immunoglobulin G Therapy Specific Questionnaire (IgGTSQ). Due to the small sample size, results were compared to 95% confidence intervals (95% CIs). Key findings Sixteen patients with available HRQoL data were included in the analysis. All SF-36v2 domains had corresponding 95% CIs that contained the US norm across visits with the exception of the General Health (GH) domain, which was lower (GH US norm, 70.85; GH upper confidence limit ranged from 64.12 to 69.43 across visits). Although the SF-36v2 minimum important differences pre-specified for comparison fell within the 95% CIs around the change from baseline in many cases, the 95% CIs also included zero, indicating stability. The EQ-5D Index Score was stable, and fell within the 95% CI of the US Norm (0.87) at each visit. The LQI reflected high quality of life due to immunoglobulin treatment; mean domain scores were between 77.3 and 92.3 across visits. The TSQM showed high levels of satisfaction following treatment; mean domain scores were between 68.4 and 93.8 across visits. The IgGTSQ indicated that patients maintained positive feelings about their current therapy (mean ≥82.2 across visits) as well as when receiving treatment at home (mean ≥86.9 across visits). Conclusion Patients continuing on Hizentra over a 96-week extension study maintained HRQoL and overall treatment satisfaction.

Improved Quality of Life, Immunoglobulin G Levels, and Infection Rates in Patients with Primary Immunodeficiency Diseases during Self-Treatment with Subcutaneous Immunoglobulin G

Primary immunodeficiency diseases (PIDDs) include a large class of genetically heterogeneous disorders which predispose patients to significant risk of serious and chronic/recurrent infections, as well as reduced quality of life (QoL). Intravenous immunoglobulin (IVIG) therapy improves the well being of PIDD patients; however, the need for venous access and potentially severe side effects frequently require administration in medical facilities. We evaluated the long-term (12-month) experience with home-based self infusions of subcutaneous immune globulin (SCIG) in patients with PIDD on health-related QoL, rates of serious bacterial infections, and all other infections. Adults (n = 42) and children (n = 9) with PIDD, previously treated with clinic-based IVIG, were trained to self administer SCIG at home. QoL (SF-36(R) and CHQ-PF50 questionnaires), serious bacterial infections, serum immunoglobulin G (IgG) levels, overall infections, and incidence of adverse events were recorded at predetermined intervals. All patients had improved perceptions of general health (adults P = 0.047, children P = 0.037). Adults also had marked improvement in the bodily pain and vitality assessments, and parents had improved perceptions of personal and family activities. Serum IgG levels were maintained at mean levels 25% higher than previous troughs on IVIG. There were 162 infections overall for an annual rate of 3.42/patient, but only 1 serious bacterial infection was observed (0.03/patient/yr). An average of 4.5 days/yr was missed from work or school per patient. Home SCIG therapy was safe and led to improved perceptions of general health, higher serum IgG levels, and very low rates of infections and days missed from work/school.

Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease

Subcutaneous administration of intravenous immunoglobulin G (IgG) preparations provides an additional level of patient convenience and more options for patients with poor venous access or a history of intravenous IgG reactions. An open-label, pharmacokinetic trial (n = 32) determined the non-inferiority of the subcutaneous versus intravenous route of 10% caprylate/chromatography purified human immune globulin intravenous (IGIV-C; Gamunex®) administration by comparing the steady-state area under the concentration-versus-time curve (AUC) of total plasma IgG in patients with primary immunodeficiency disease. Patients on stable IGIV-C received two intravenous infusions (administered 3 or 4 weeks apart). Seven to 10 days after the second intravenous infusion, all patients switched to a weekly infusion of subcutaneous IGIV-C, with the dose equal to 137% of the previous weekly equivalent intravenous dose, for up to 24 weeks. Samples for pharmacokinetic analysis were collected during steady state for intravenous and subcutaneous IGIV-C treatments. The AUC(0-) τ geometric least-squares mean ratio was 0·89 (90% confidence interval, 0·86-0·92) and met the criteria for non-inferiority. The overall mean steady-state trough concentration of plasma total IgG with subcutaneous IGIV-C was 11·4 mg/ml, 18·8% higher than intravenous IGIV-C (9·6 mg/ml). Subcutaneous IGIV-C was safe and well tolerated. Subcutaneous IGIV-C infusion-site reactions were generally mild/moderate and the incidence decreased over time. No serious bacterial infections were reported. Weekly subcutaneous IGIV-C infusion using 137% of the weekly equivalent intravenous immunoglobulin dose provides an AUC comparable to intravenous administration, thus allowing patients to maintain the same IgG preparation/formulation if switching between intravenous and subcutaneous infusions.

Pharmacokinetics and Safety of Subcutaneous Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Patients with Primary Immunodeficiency Disease (PID)

Pharmacokinetics and Safety of Subcutaneous Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Patients with Primary Immunodeficiency Disease (PID)

Effective Use of Subcutaneous Immune Globulin (SCIG) for an Infant with X-linked Agammaglobulinemia (X-LA)

Effective Use of Subcutaneous Immune Globulin (SCIG) for an Infant with X-linked Agammaglobulinemia (X-LA)

Immune Globulin for Patients with Primary Immune Deficiency: An Evidence Based Practice Guideline

Background: The original use of immune globulin (IG) was for replacement in patients with primary immune deficiency (PID). The evidence supporting this stems from the 19650s; however there have not been any rigorously developed evidence based clinical practice guidelines (CPGs) for the use of IG for PID. In 2007, Canadian Blood Services and the National Advisory Committee on Blood and Blood Products in Canada convened a panel of Canadian immunologists and a methodologist to develop a CPG for the use of IG in patients with PID. The objectives of this guideline areto examine the evidence for the use of IG in patients who have PID andto provide guidance for practitioners involved in the care of PID patients and transfusion medicine specialists on the use of IG.Methods: The panel identified key clinical questions and a systematic, expert and bibliography literature search up to July 2008 was conducted to ensure all relevant publications were included. The panel generated recommendations based on the evidence. The levels of evidence and grading of recommendations were adapted from the Canadian Task Force on Preventative Health Care. To validate conclusions and recommendations, the practice guideline will be sent to immunologists internationally and to a patient representative in September 2008. The guideline will be disseminated to all immunologists, internists and pediatricians in Canada to aid implementation of the guideline. The National Advisory Committee of Blood and Blood Products in Canada will assess the performance of the guideline and will renew the guideline at timely intervals.Results and Conclusions: The panel identified the following key clinical questions:what is the prevalence of the PIDs that require IG;does treatment with IG improve morbidity and mortality; andwhat criteria should be used to monitor the effectiveness of IVIG.The literature search was conducted in August 2007 and updated to July 2008. 1087 citations were reviewed. 101 reports, 1 systematic review and 3 consensus documents/guidelines were included. Current estimates suggest PID is under-diagnosed. Although more than 75% of patients require IG at some point in their treatment, the actual incidence of requiring IG is unknown. There is ample evidence that IG reduces infections, hospitalization and days lost from work/school. There is some evidence to suggest that IG may ameliorate chronic illnesses in patients with PID however, there is no data of the effect of IG on malignancy and insufficient data on the effect of IG on autoimmune disease in this patient population to make a recommendation. Quality of life (QoL) has not been adequately assessed in the literature; however the reduction in infections and hospitalizations likely translates to an improved QoL. Although, there is no evidence to suggest clinical superiority of one IVIG formulation over another, for patients with autoimmune manifestations and PID, there is insufficient evidence that subcutaneous IG is equivalent to IVIG. The vaccination of these patients is an evolving field. Due to the complex nature of the management of patients with PID, the panel recommended assessment by an immunologist prior to the initiation of IG and monitoring by a comprehensive care clinic. Clinical outcomes such as frequency of infections, hospitalization, days missed from school/work should be used to monitor the effectiveness of IVIG. Specific recommendations for dosing and interval of IG therapy were made within the guideline based on the literature The development of a national registry for patients with primary immune deficiency, and the development of a surveillance system for adverse events from IG particularly infections were considered priorities for future development.

Improving Quality of Life at Home for Pediatric Patients and Families With Primary Immune Deficiencies Using Subcutaneous Immune Globulin Infusions

Pediatric patients diagnosed with primary antibody deficiencies often require lifelong immune globulin replacement to help protect them from life-threatening infections. Although this is not a cure or a treatment for the disorder, replacement therapy is necessary to maintain health. The two current viable routes for immune globulin replacement are intravenous or subcutaneous. For many patients, subcutaneous infusions improve quality of life by offering greater independence and better control of the therapy situation and daily life. Subcutaneous infusions have been shown to be easy for both adult patients and children and their parents and to be safe, with minimal or no systemic reactions and no transmission of the hepatitis C virus. All of these factors are very important when considering replacement therapy. Home nursing care and support can also help provide additional support to improve treatment outcomes to enhance quality of life.