Subcutaneous Administration Of IgG Research Articles

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020. Total IgG used within 5 years increased by 27.48%, IgG use/1000 inhabitants/year was 23.13 g (2016) and 29.61 g (2020). In 2020, 35.5 % of IgG used was for neurological conditions, 25% for primary immunodeficiencies (PID), and 39.3% for all other indications. Within 5 years, 1,121,168.75 g IgG was used in PID; the use increased by 72%, from 783 in 2016 to 1153 patients in 2020. The proportion of patients who received subcutaneous immunoglobulin (SCIG) replacement therapy (IgRT) increased to 78% (2020). Within 5 years, 1,783,534.81 g IgG was used in neurological drug programs (+42.44%) and 2,327,513.88 g (+1.25%) outside neurological indications and outside PID. The annual IgG amount decreased in adult anesthesiology and intensive care (-46%), internal medicine (-55%), pneumonology (-50%), pediatric clinical immunology (-50%), and gynecology and obstetrics (-48%) and increased in dermatology (+178%), rheumatology (+103%), and clinical transplantation (+82%). IgG use significantly increased in Poland, mostly owing to PID. Subcutaneous IgG administration is currently the most common mode of IgRT in PID patients. An increase in SCIG administration may be expected for other indications. Implementing evidence-based clinical guidelines is key to prioritizing and rationalizing IgG use for immunomodulatory indications and secondary immune deficiencies.

SCIG administration: A promising and patient convenient alternative for those receiving long-term IVIG.

Background: Intravenous immunoglobulin (IVIG) therapy has been used as antibody replacement therapy in primary immunodeficiency diseases (PID) for more than 50 years. In this study, we aimed to define IVIG usage and adverse reactions and complications in PID and explain how subcutaneous immunoglobulin (SCIG) replacement therapy is an alternative that improves the patient experience. In addition, the additional nursing responsibilities associated with this service were also identified.Methods: Data and service satisfaction surveys for the last 10 years were reviewed from the Allergy and Immunology Division log registry for those on IVIG and SCIG.Results: IVIG practice: Most patients currently on IVIG in our unit have PID. Adverse reactions occur during the initial 30 to 60 minutes of the infusion and are mild and self-limited. Infusion reactions are more likely to occur in patients receiving IVIG for the first time. Infusion-related complications included pyrogenic reactions, allergic reactions, and vasomotor symptoms. Complications reported in the literature such as the transmission of blood-borne pathogens and other serious complications, including thrombotic events, renal adverse events, and aseptic meningitis were never reported. Pyrogenic reactions occurred at a rate ≥ 100 mL/hr in at least 3 patients, and a slower infusion rate of ≤ 75 mL/hr mitigated this rate-related complication.SCIG program: This program started in Qatar in 2017. Usually, the clinician assesses and evaluates several factors to help select candidates for this therapy, including the perceptions of inconvenience and/or pain of IV infusions, presence of difficult vein access, and other relevant clinical and social factors. Once training in the appropriate techniques has been accomplished (3–6 sessions), it is most often self-administered in the home setting by the patient or a parent for a child. Table 1 summarizes patients on SCIG.Additional nursing responsibilities: The nursing role in subcutaneous IgG administration is primarily that of an educator and to help the patient/family become independent. This can be achieved by the assessment of appropriate patient selection for self-administration. Determining which patients are suitable include adequate patient education with return demonstration of the necessary skill set, monitoring parameters, educating patients about their medication, and providing educational resources and support.Conclusion: SCIG administration can be a convenient alternative for patients with PID receiving long-term IVIG.

Feasibility of switching from intravenous to subcutaneous immunoglobulin in CIDP: PATH trial and clinical experience

The PATH study showed efficacy of subcutaneous IgG administration (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated the feasibility of switching from intravenous IgG (IVIG) to SCIG in CIDP patients according to PATH data and clinical experience. In PATH, CIDP patients were randomized to SCIG (0.2 or 0.4 g/kg/week) or placebo after IVIG restabilization. Observational studies of switching from IVIG to SCIG in CIDP and multifocal motor neuropathy are also considered. Forty-eight% of PATH subjects experienced ⩾ 1 adverse event (AE) with IVIG (rate: 0.175/infusion). Corresponding percentages for SCIG-0.2 and SCIG-0.4 were 58% and 52% (0.08 and 0.05/infusion). The most common AE was headache for IVIG (16%), and local infusion site reactions for SCIG (19% and 29%). Most subjects (88%) felt SCIG was easier to use versus IVIG. More subjects (p In observational studies, switching from IVIG to SCIG (1–5 infusion[s]/week) was associated with reduced incidence of AEs (22% vs. 1%, and 60% vs. 0%, IVIG vs. SCIG), improved QoL and higher patient preference for SCIG versus IVIG (69–90%). The PATH trial and observational studies document the feasibility, safety and efficacy of SCIG therapy in CIDP.

Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies.

In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra®) has been developed and has replaced Vivaglobin® (SCIG 16%).An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra® would affect frequency of infusions, number of infusion sites, patients’ satisfaction, and tolerability in patients previously treated with Vivaglobin® or intravenous immunoglobulins (IVIG).Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra® with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra®, with respect to the medicinal product formerly used, and the variations in patients’ therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded.Eighty-two patients switched to Hizentra®: 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin®. The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra®). A decrease in the number of infusion sites with Hizentra® was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra®; no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported.

Comparison of Clinical Outcomes and Laboratory Measures in Patients with Common Variable Immunodeficiency on Subcutaneous Immunoglobulin Replacement Versus Intravenous Immunoglobulin Replacement

Immunoglobulin replacement can be life-saving for certain individuals with immunodeficiencies. Several options for IgG replacement exist, including preparations of both intravenous (IVIG) and subcutaneous IgG (SCIG) replacement. SCIG administration is an increasingly used method of replacement with potential advantages including fewer systemic side effects, no need for IV access, patient-reported improved quality of life, and decreased cost. In addition, patients with associated co-morbidities, for instance, those that cause protein loss, may demonstrate more stable, consistent IgG levels on subcutaneous replacement when compared to intravenous replacement.

Open-label study on treatment with 20 % subcutaneous IgG administration in polymyositis and dermatomyositis

The objective of this study is to describe the benefit of 20 % subcutaneous infusions of immunoglobulin (SCIg) in patients with dermatomyositis (DM) or polymyositis (PM) after a switch from previous 16 % SCIg treatment. Eight patients with DM or PM, who met the Bohan and Peter's criteria, previously treated with 16 % SCIg, were switched to weekly 20 % SCIg infusions (Hizentra®; CSL Behring) at doses equivalent to their previous subcutaneous treatment. A standardised protocol was used to evaluate patients, disease activity and treatment response. The disease remained stable in three and improved in four other patients, as documented by increased Medical Research Council scores and normal serum CK levels. No relapse of disease occurred. Local reactions were mild and self-limiting. No serious adverse events were reported. The mean duration of infusion per week was significantly lower compared to the mean duration of the 16 % SCIg preparation. A specifically designed questionnaire documented the patients' satisfaction with treatment. The weekly administration of 20 % SCIg is effective in maintaining a quiescent disease in patients with DM or PM with no increased safety concerns. SCIg therapy is particularly attractive for patients because it does not require venous access and hospitalisation and requires less assistance from healthcare provider services. The administration of 20 % SCIg was beneficial and safe in maintaining a quiescent disease and in inducing a complete remission in moderately active disease in patients with DM or PM. The treatment with 20 % SCIg led to the possibility to discontinue and to reduce the use of glucocorticoids and/or the immunosuppressants. Patients reported their satisfaction in terms of contact with health professionals, quality of treatment-related information and administration convenience, with an improved quality of life.

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.

Subcutaneous immunoglobulin replacement therapy with Hizentra®, the first 20% SCIG preparation: a Practical approach

To reduce the risk of infection in adults and children with primary immunodeficiencies, replacement therapy with IgG, which can be administered to patients intravenously or subcutaneously, is required. Although intravenous administration of IgG (IVIG) has been the therapy of choice in the US and widely used in Europe for many years, subcutaneous administration of IgG (SCIG) has recently gained considerable acceptance among patients and doctors. SCIG therapy achieves high and stable serum IgG levels, is well tolerated, and can be self-administered. Hizentra (IgPro20; CSL Behring, Berne, Switzerland) is the first, ready-to-use 20% liquid preparation of human IgG specifically formulated for subcutaneous infusions. The high concentration (20%) might allow shorter infusion times due to smaller infusion volumes, with potential improvement in the convenience of SCIG therapy. Hizentra is well tolerated and has been shown to protect adult and pediatric primary immunodeficiency patients against serious bacterial infections. In addition, it is easy to handle and can be stored at a temperature up to 25°C. In summary, Hizentra is an advance in the field of immunoglobulin replacement therapy, which might offer benefits for home therapy patients.

Subcutaneous Administration of IgG in Primary Immune Deficiency Patients Results in Higher Trough Serum IgG Levels and Decreased Morbidity as Compared to IV Administration

Subcutaneous Administration of IgG in Primary Immune Deficiency Patients Results in Higher Trough Serum IgG Levels and Decreased Morbidity as Compared to IV Administration

Prospective Study on CVID Patients with Adverse Reactions to Intravenous or Subcutaneous IgG Administration

The multicenter prospective study provides information on adverse reactions to intravenous and subcutaneous immunoglobulin treatment in a cohort of 262 patients with common variable immunodeficiency. Severe adverse reactions are a rare but unpredictable event that might occur also in patients who tolerate substitutive intravenous or subcutaneous immunoglobulin therapy for months or years. Subcutaneous therapy has been proved to be a safe option in the 13 patients who had to stop intravenous treatment and who remained out of immunoglobulin replacement for long periods of time. However, severe reactions to subcutaneous therapy occurred at the first or after several subcutaneous immunoglobulin administrations in 2 out of 13 patients. Therefore, patients with previous severe reactions to intravenous immunoglobulin should be considered at particularly high risk for reaction to subcutaneous administration. In these cases, switching from in-hospital administration to home self-administration should be done with extreme care.

Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home

A large number of children and adults with primary antibody deficiencies need lifelong IgG replacement therapy. It is mostly unknown what effect the choice of replacement therapy has on the patients' health-related quality of life (HRQOL) and treatment satisfaction (TS). To investigate whether a switch from hospital-based intravenous IgG (IVIG) to home-based subcutaneous IgG (SCIG) therapy would improve the HRQOL and TS. Fifteen children (<14 years; hospital-based IVIG therapy at enrollment) and 32 adults (> or =14 years; 22 on hospital-based IVIG and 10 on home-based SCIG therapy at enrollment) were included. Questionnaires were completed at baseline and at 6 and 10 months: the Child Health Questionnaire-Parental Form 50 (children) or Short Form 36 (adults), the Life Quality Index, and questions regarding therapy preferences. The SCIG home therapy was reported to give better health (P=.001) and improved school/social functioning (P=.02) for the children, reduced emotional distress (P=.02) and limitations on personal time for the parents (P=.004), and fewer limitations on family activities (P=.002). Adults switching therapy reported improved vitality (P=.04), mental health ( P=.05), and social functioning ( P=.01). Adults already on SCIG home therapy at enrollment retained high HRQOL and TS scores. The SCIG home therapy improved TS because it led to greater independence and better therapy convenience ( P <.05). The patients preferred the SCIG administration route and having the treatment at home. Home-based SCIG therapy improves several important aspects of HRQOL and provides the patients with primary antibody deficiencies and their families with greater independence and better control of the therapy situation and daily life. SCIG home therapy is an appreciated therapeutic alternative for adults and children in need of lifelong IgG replacement therapy.