Subcutaneous Immune Globulin Research Articles

Real-World Evidence of Tolerability of 20% Subcutaneous Immunoglobulin Treatment

PurposeThe safety and efficacy of subcutaneous immune globulin 20% (human) solution (Ig20Gly) were demonstrated in clinical trials. However, real-world evidence of the tolerability of self-administered Ig20Gly in elderly patients is lacking. We describe real-world patterns of Ig20Gly usage for 12 months in patients with primary immunodeficiency diseases (PIDD) in the USA.MethodsThis retrospective chart review of longitudinal data from 2 centers included patients aged ≥ 2 years with PIDD. Ig20Gly administration parameters, tolerability, and usage patterns were assessed at initial and subsequent 6- and 12-month infusions.ResultsOf 47 enrolled patients, 30 (63.8%) received immunoglobulin replacement therapy (IGRT) within 12 months before starting Ig20Gly, and 17 (36.2%) started IGRT de novo. Patients were predominantly White (89.1%), female (85.1%), and elderly (aged > 65 years, 68.1%; median age = 71.0 years). Most adults received at-home treatment during the study, and most self-administered at 6 months (90.0%) and 12 months (88.2%). Across all time points, infusions were administered at a mean rate of 60–90 mL/h/infusion, using a mean of 2 sites per infusion, on a weekly or biweekly frequency. No emergency department visits occurred, and hospital visits were rare (n = 1). Forty-six adverse drug reactions occurred in 36.4% of adults, mostly localized site reactions; none of these or any adverse events led to treatment discontinuation.ConclusionThese findings demonstrate tolerability and successful self-administration of Ig20Gly in PIDD, including elderly patients and patients starting IGRT de novo.

Transition to Subcutaneous Immune Globulin 16.5% Improves Patient-Reported Quality of Life

Subcutaneous immune globulin (IGSC) offers the convenience of self-administration, fewer systemic reactions, and more stable IgG levels compared to intravenous IG (IVIG). The Life Quality Index (LQI) is an instrument to evaluate health-related quality of life (QoL) and treatment satisfaction among patients receiving IG therapy and has been previously applied to product switches. We report QoL survey results for patients transitioned to IGSC 16.5% (Cutaquig®) from IVIG or alternative IGSC in a real-world setting.

Infusion parameters of 20% subcutaneous immunoglobulin for primary immunodeficiency diseases among patient support program participants

BackgroundThe safety and efficacy of subcutaneous immune globulin 20% (human) solution (Cuvitru; Ig20Gly) for primary immunodeficiency disease (PID) have been demonstrated in 2 pivotal trials. ObjectiveTo describe patient characteristics and infusion parameters of patients with PID initiating Ig20Gly outside of a clinical trial setting. MethodsThis retrospective, observational study analyzed records of patients participating in the HelloCuvitru program, a patient support program in the United States providing Ig20Gly free of charge for the first 4 infusions to patients aged 2 years or older who had PID and no previous experience of Ig20Gly. Data were collected retrospectively from patient records and during nurse visits. ResultsA total of 817 patients (88% of 931 enrolled) completed 4 infusions. At the fourth Ig20Gly infusion, the median (interquartile range) dose was 0.55 (0.46-0.69) g/kg/mo, infusion rate per site was 40 (30.0-50.0) mL, and infusion rate per site was 47 (42.5-53.3) mL/h/site. By the fourth infusion, most patients (58%) received Ig20Gly at 2 infusion sites every 7 (30%) or 14 (25%) days. Median prescribed Ig20Gly dose per month was similar across age groups; median infusion volume per site increased with age. Most patients younger than 18 years received infusions every 14 days; patients aged 18 years or older were more likely to receive infusions weekly. Infusion parameters were similar regardless of whether patients received previous immunoglobulin subcutaneously or intravenously. ConclusionIn this large, real-world population of patients with PID, most Ig20Gly infusions were administered for less than 1 hour and required fewer than 2 infusion sites, consistent with the pivotal trials. Infusion rate per site was similar regardless of age, previous immunoglobulin treatment, or infusion frequency.

Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin

Patients with primary immunodeficiency diseases often require lifelong immunoglobulin (IG) therapy. Most clinical trials investigating IG therapies characterize serum immunoglobulin G (IgG) pharmacokinetic (PK) profiles by serially assessing serum IgG levels. This retrospective analysis evaluated whether steady-state serum IgG trough level measurement alone is adequate for PK assessment. Based on individual patient serum IgG trough levels from two pivotal trials (phase 2/3 European [NCT01412385] and North American [NCT01218438]) of weekly 20% subcutaneous IG (SCIG; Cuvitru, Ig20Gly), trough level-predicted IgG AUC (AUCτ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUCτ). In both studies, mean AUCτ,tp values for Ig20Gly were essentially equivalent to AUCτ with point estimates of geometric mean ratio (GMR) of AUCτ,tp/AUCτ near 1.0 and 90% CIs within 0.80–1.25. In contrast, for IVIG, 10%, mean AUCτ,tp values were lower than AUCτ by >20%, (GMR [90% CI]: 0.74 [0.70–0.78] and 0.77 [0.73–0.81] for the two studies, respectively). Mean AUCτ,tp values calculated for 4 other SCIG products (based on mean IgG trough levels reported in the literature/labels) were also essentially equivalent to the reported AUCτ (differences <10% for all except HyQvia, a facilitated SCIG product), while differences for IVIG products were >20%. In conclusion, steady-state serum IgG levels following weekly SCIG remain stable, allowing for reliable prediction of AUC over the dosing interval using trough IgG levels. These findings indicate that measuring steady-state serum IgG trough levels alone may be adequate for PK assessment of weekly SCIG.

Update on real-world use of facilitated subcutaneous immunoglobulin and immune globulin subcutaneous (human) 20% solution in patients with immunodeficiencies: poster extracts from the 19th Biennial Meeting of the European Society for Immunodeficiencies

ABSTRACT Immunoglobulin replacement therapy has been shown in clinical trials to be an important therapeutic option for reducing the incidence of serious bacterial infections and improving the quality of life in patients with primary and secondary immunodeficiencies (PID and SID, respectively). This article summarizes a poster series presented at the 19th Biennial Meeting of the European Society for Immunodeficiencies (October 14–17, 2020) further evaluating real-world usage and patient/physician experience with Immune Globulin Subcutaneous (Human) 20% Solution (Ig20Gly) in patients with PID and facilitated subcutaneous immunoglobulin (fSCIG) in patients with PID or SID.

AB0552 CHARACTERISTICS OF MYOSITIS SPECTRUM DISEASE - RHEUMATOID ARTHRITIS OVERLAP CASES IN A HUNGARIAN COHORT

Background:Overlap syndromes are autoimmune disorders in which classification criteria of at least two connective tissue diseases (CTDs) are fulfilled. The Division of Clinical Immunology in Debrecen, Hungary oversees patients with idiopathic inflammatory myopathies (IIMs) since the 1980’s.Objectives:In a work called The Myositis Antibody Research Project, which is coordinated together with the Bath Institute for Rheumatic Diseases (UK), authors investigated 330 patients with myositis, all treated in this Hungarian center.Methods:The aim of this retrospective study was to investigate the frequency, clinical and serological parameters and therapeutic options in myositis – rheumatoid arthritis overlap cases in this group of 330 patients.Results:The frequency of overlap cases, as seen in literature, was 13.64%. The importance of myositis-associated antibodies (MAAs) can be seen on this results: 44.44% of overlap patients, while only 7.02% of not overlap patients were MAA positive. Out of our 45 overlap patients twenty-seven myositis - RA overlap patients could be identified. Among these 27 patients the women:men ratio was 12.5:1, PM:DM ratio was 2.375:1. Muscle weakness and sceletal involvement was present in every patient, myalgia in 77.78% and Raynaud’s phenomenon in 48.15% of the patients; general symptoms during disease relapse (fatigue, weight loss, fever) were present in 59.26%, 18.52% and 14.82%, respectively. Ten cases had seropositive rheumatoid arthritis, with high titer of rheumatoid factor. Authors underline the importance of lung involvement as internal organ manifestation: 8 patients had anti-synthetase antibodies (six anti-Jo-1, one anti-PL-7 and one anti-PL-12). In anti-PL-7 and anti-PL-12 positive patients interstitial lung disease (ILD) appeared some years before myositis and early agressive management of ILD resulted in fast remission of muscle weakness. Anti-Mi-2 and anti-SRP could be detected in two patients. Most frequent used disease modifying antirheumatic drugs were cyclophosphamide, methotrexate and cyclosporine, 19 patients received DMARD combination therapy. Biological therapy was used in 3 patients, intravenous or subcutaneous immuneglobulin in 4 patients and one patient with RA – myositis – antiphospholipid syndrome died because of asipartion pneumonia.Conclusion:Authors conclude that it is really challenging to treat these overlap cases: they form a very heterogenous group of patients and management has to be personalized.Disclosure of Interests:None declared

Clinical Practice Experience with HyQvia in Adults Using Alternative Dosing Regimens and Pediatric Patients: A Retrospective Study.

IntroductionHyQvia (Immune Globulin Infusion 10% [Human] with Recombinant Human Hyaluronidase) was developed to combine the advantages of intravenous and subcutaneous immune globulin (SCIG), allowing administration of larger volumes at a single subcutaneous site with less frequent dosing when compared to other SCIG products. Current US prescribing guidelines for HyQvia are limited to adults and do not encompass the flexibility required to achieve success in all patients with primary immunodeficiency (PID).MethodsThis retrospective study was designed to evaluate the clinical experience of treating patients with PID with HyQvia regimens outside of package insert recommendations as well as in pediatric patients. Data were abstracted from 38 patient records (317 HyQvia infusions), including five patients less than 16 years of age, from seven US immunology clinics.ResultsAmong 37 patients receiving HyQvia regimens differing from prescribing guidelines, the most notable variations included shorter ramp-up periods, use of two rather than one infusion site, and slower than maximal infusion rates to mitigate local adverse events (AEs). The medication volume infused for single site doses ranged from 75 to 200 mL and doses split between two sites ranged from 100 to 750 mL. The most common type of regimen variation was a condensed ramp-up phase (shorter schedule, higher doses), and 96% (24/25) of patients managed in this way completed ramp-up. The most common ramp-up schedule was three infusions (one at 25–45%, another at 50–75%, and the final at 100% of target dose) spread over 2–4 weeks.ConclusionsA shorter ramp-up schedule did not appear to increase the number of AEs compared to standard ramp-up schedules. For patients with AEs, slower infusion rates and the use of two sites may improve medication tolerability. Four of five pediatric patients reported no AEs, and only one discontinued, stating a fear of needles. HyQvia may be tailored to adults requiring alternative rates, ramp-up, and/or dosing regimens and may be especially well-suited to children.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01264-7) contains supplementary material, which is available to authorized users.

Tolerability of Ig20Gly during onboarding in patients with primary immunodeficiency diseases

BackgroundThe subcutaneous immune globulin (SCIG) 20% product, Ig20Gly, was shown to be efficacious and well tolerated in 2 phase 2/3 North American and European studies at infusion volumes up to 60 mL/site and rates up to 60 mL/h/site in patients with primary immunodeficiency diseases. ObjectiveTo assess patient experience after switching to Ig20Gly with fast infusion rates and large infusion volumes/site in the North American study. MethodsIn this analysis of the open-label phase 2/3 study in which patients aged ≥2 years received weekly Ig20Gly infusions for up to approximately 1.3 years, tolerability and infusion parameters were assessed throughout the study for all patients and by prestudy treatment regimen (intravenous [IV] switchers or SC switchers). ResultsOverall, 61% of patients reached the infusion rate of ≥60 mL/h/site and continued at this rate for 1 or more subsequent infusions; the median infusion number when patients first reached ≥60 mL/h/site was 3. No association was found between higher infusion volumes or rates and increased incidences of local and systemic adverse events (AEs) in the total population and patients younger than 16 years. Infusion parameters and tolerability were generally comparable regardless of the route of prestudy treatment (IV or SC switchers); however, IV switchers experienced lower rates of local AEs than SC switchers and had a slightly higher median infusion volume per site and longer infusion duration vs SC switchers. ConclusionHigh Ig20Gly infusion rates of at least 60 mL/h/site and volumes ≥60 mL/site were well tolerated during onboarding and throughout treatment, regardless of prestudy treatment. Trial Registration: ClinicalTrials.gov Identifier NCT01218438.

IG20GLY TOLERABILITY AND INFUSION CHARACTERISTICS ACROSS AGE GROUPS IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES

Introduction Subcutaneous immune globulin 20%, Ig20Gly, was well tolerated in the phase 2/3 North American study in patients with primary immunodeficiency diseases (PIDD). Here we analyze the safety, tolerability, and infusion parameters by age groups. Methods Patients aged ≥2 years with PIDD received weekly Ig20Gly infusions at volumes ≤60 mL/site and rates ≤60 mL/h/site for ∼1.3 years in the North American study (NCT01218438). Adverse events (AEs), tolerability, and infusion parameters were assessed in 74 patients (2- Results Overall, 71.6% (53/74) of patients achieved a maximum infusion rate ≥60 mL/h/site. Median maximum infusion rates and volumes/site were higher in adults (16–[60 mL/h/site; 45.3 mL/site]; ≥65 y [60 mL/h/site; 39 mL/site]) and adolescents aged 12–5–Percentages of infusions associated with causally related AEs were low among all pediatric age groups (0% [2–[5–12–3.1% [16–; there were no serious or severe causally related AEs. Ig20Gly infusions were well tolerated by all age groups; >99% of infusions were administered without an infusion rate reduction, interruption, or discontinuation due to AEs. Conclusions Ig20Gly infused at relatively high rates and volumes was well tolerated in patients of all ages with PIDD.

Infusion Parameters and Adverse Events in Patients With Primary Immunodeficiency Diseases Who Switched to Subcutaneous Human Immune Globulin 20% (Ig20Gly) From Intravenous or Subcutaneous Immune Globulin

Infusion Parameters and Adverse Events in Patients With Primary Immunodeficiency Diseases Who Switched to Subcutaneous Human Immune Globulin 20% (Ig20Gly) From Intravenous or Subcutaneous Immune Globulin

Onboarding Experience of Patients With Primary Immunodeficiency Diseases Who Switched to Subcutaneous Human Immune Globulin 20% (Ig20Gly) From Intravenous or Subcutaneous Immune Globulin 10%

Onboarding Experience of Patients With Primary Immunodeficiency Diseases Who Switched to Subcutaneous Human Immune Globulin 20% (Ig20Gly) From Intravenous or Subcutaneous Immune Globulin 10%

Unique urticarial presentation of minocycline-induced lupus erythematosus

The association between guttate psoriasis and infection with group A Streptococcus (GAS) has been well established in the medical literature. However, responses to treatments aimed at GAS eradication such as systemic antibiotics or tonsillectomy are inconsistent. Further complicating treatment recommendations for a disease with a suspected microbial trigger, the standard therapy for severe psoriasis is with systemic immunosuppressant medications. This case report illustrates the role of GAS as a trigger for acute onset severe psoriasis in a child whose skin disease initially worsened with a trial of methotrexate. An immune evaluation confirmed a co-existing selective antibody deficiency. Subsequent treatment with intravenous immune globulin dramatically improved his underlying immune function and decreased GAS infections. This improvement in overall immune function and decrease in GAS infections cleared his skin disease. An interval change in formulation to subcutaneous immune globulin was not as effective.

Treatment of selective antibody deficiency with IVIG resulting in decreased frequency of streptococcal infection and improvement of guttate psoriasis

The association between guttate psoriasis and infection with group A Streptococcus (GAS) has been well established in the medical literature. However, responses to treatments aimed at GAS eradication such as systemic antibiotics or tonsillectomy are inconsistent. Further complicating treatment recommendations for a disease with a suspected microbial trigger, the standard therapy for severe psoriasis is with systemic immunosuppressant medications. This case report illustrates the role of GAS as a trigger for acute onset severe psoriasis in a child whose skin disease initially worsened with a trial of methotrexate. An immune evaluation confirmed a co-existing selective antibody deficiency. Subsequent treatment with intravenous immune globulin dramatically improved his underlying immune function and decreased GAS infections. This improvement in overall immune function and decrease in GAS infections cleared his skin disease. An interval change in formulation to subcutaneous immune globulin was not as effective.

Aseptic meningitis following therapy with immune globulins: a combination of product features and patient characteristics?

Aseptic meningitis (AM) represents a recognized side effect of immune globulin (IG) therapy and may warrant additional diagnostic procedures and therapy with anti-infective drugs until a definite diagnosis can be established. Although, to date, only small case series have been published, the objective of the current study was to investigate a large case series of patients with AM. The pharmacovigilance safety database of a 10% liquid IG (Gammagard Liquid) was queried for all reports of AM. Patient demographics, treatment-specific data, and product-specific data were determined. The proportional reporting rates of AM were compared according to the route of administration (intravenous vs. subcutaneous) and molecular size distribution of IG lot (dimer content ≥ 8 vs. < 8%). In total, 144 AM episodes were reported in 136 distinct patients. Females were affected by AM nearly four times more than males. AM was not limited to patients who received high-dose IG therapies but was observed in those who received low-dose regimens in percentages comparable to the estimated usage patterns of IG. Lots that had high dimer values were associated with AM significantly more often than lots that had low dimer values (p < 0.001), and subcutaneous IG administration was associated with lower rates of AM compared with intravenous IG administration (p = 0.055). In contrast to previously published data, AM was observed in both low-dose and high-dose regimens without favoring high IG doses, and females were affected nearly four times more often than males. Immunoglobulin G dimers may play a role in the etiology of AM, and subcutaneous administration may be associated with a lower rate of AM compared with intravenous administration.

Human immune globulin infusion in the management of multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a debilitating and rare disease causing profound weakness with minimal to no sensory symptoms. Conduction block is frequently seen on electrodiagnostic testing. An immune-mediated pathology is suspected though the exact underlying pathophysiology has yet to be elucidated. The presence of anti-GM1 ganglioside IgM antibodies coupled with favorable response to intravenous and subcutaneous immunoglobulins supports a complement-mediated mechanism which leads to destruction of nerve tissue with probable predilection to the nodes of Ranvier. High-dose immunoglobulin currently is the only treatment with proven efficacy for MMN patients. Unfortunately, many patients experience decreased responsiveness to immunoglobulins over time, requiring higher and more frequent dosing. In this review, we will focus on the pharmacology, efficacy, safety, and tolerability of intravenous and subcutaneous immune globulin infusion for treatment of MMN.

Patients with Rheumatologic Disorders May Develop Pain with Immunoglobulin Replacement, Requiring the Use of Daily Subcutaneous Therapy

Intravenous immune globulin (IVIG) has been associated with systemic side effects including back and joint pain. Subcutaneous immune globulin (SCIG) has a lower incidence of systemic side effects including pain. Patients with existing rheumatologic disease may be at risk for joint pain following IVIG/SCIG infusion.

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.

Incorporating Treatment into Life: A Retrospective Analysis of Clinical, Financial and Quality of Life Measures Following Hematopoietic Stem Cell Transplant in Patients Receiving Home Subcutaneous Immune Globulin

Incorporating Treatment into Life: A Retrospective Analysis of Clinical, Financial and Quality of Life Measures Following Hematopoietic Stem Cell Transplant in Patients Receiving Home Subcutaneous Immune Globulin

Efficacy and safety of Hizentra®, a subcutaneous immune globulin, in Japanese patients with primary immunodeficiency diseases

Efficacy and safety of Hizentra®, a subcutaneous immune globulin, in Japanese patients with primary immunodeficiency diseases

Tolerability and Efficacy of 20% Subcutaneous Immune Globulin (ScIg) Delivered by Rapid Push

Tolerability and Efficacy of 20% Subcutaneous Immune Globulin (ScIg) Delivered by Rapid Push