Real-World Use, Safety, and Patient Experience of 20% Subcutaneous Immunoglobulin for Primary Immunodeficiency Diseases.

INTRODUCTION: The CORE study aimed to provide a detailed understanding of real-world immune globulin subcutaneous (human) 20% solution (Ig20Gly) utilization in patients with primary immunodeficiency diseases (PIDs) in Germany and Switzerland. METHODS: Patients with PIDs receiving a stable dose of any subcutaneous immunoglobulin for ≥ 3 months before enrollment were eligible for this multicenter (n = 5), phase 4, non-interventional, prospective, longitudinal cohort study. Besides baseline demographics and clinical characteristics, Ig20Gly utilization and safety data, and patient-reported outcomes (Life Quality Index/Treatment Satisfaction Questionnaire for Medication) were collected at baseline, 6 and 12 months. Statistical analysis was descriptive. RESULTS: Overall, 36 patients provided data at baseline [69.4% female; mean age: 41.6 years (7-78 years)]. Totals of 23 and 26 patients attended 6- and 12-month visits, respectively; 16 attended all three visits. One patient withdrew consent before 6-month follow-up. Median maximum infusion rates of Ig20Gly at baseline, 6 months, and 12 months were 26.7, 24.5, and 40.0 mL/h, respectively (10-60 mL/h). Infusion and dosing parameters remained consistent across time points: patients used a median of two infusion sites, primarily the abdomen, and all patients used an infusion pump; all but one infused at home and most self-administered Ig20Gly (80.8-83.3%) at once-weekly intervals (69.2-73.9%). During follow-up, 10 adverse events were reported: none were rated serious, while 2 were considered probably related to Ig20Gly. Total patient-reported outcome scores remained high throughout the study. CONCLUSION: The CORE study provides real-world evidence of the flexibility, feasibility, safety, and tolerability of Ig20Gly infusions, at mostly weekly intervals, over 1 year in patients with PIDs. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00014562. Registered April 9, 2018, https://drks.de/search/en/trial/DRKS00014562.

Primary immunodeficiency diseases are rare diseases that make patients more likely to develop infections than the general population. Many patients with primary immunodeficiency diseases do not produce enough antibodies, which are an important part of the immune system that fight infection. Replacing antibodies is the main way to treat primary immunodeficiency diseases and reduce the risk of infection. Ig20Gly is a type of medication used to replace antibodies and treat primary immunodeficiency diseases. Patients receive Ig20Gly through a needle inserted under the skin and can learn to do this themselves at home. Ig20Gly can be delivered more quickly than other antibody treatments that are less concentrated. CORE was a study of 36 patients (children and adults) taking Ig20Gly for primary immunodeficiency diseases for 1 year in Germany and Switzerland. The aim of the study was to understand how patients use and experience Ig20Gly as part of their normal treatment. In this study, nearly all patients received Ig20Gly treatment at home, and most patients gave Ig20Gly to themselves once a week. A few patients developed serious bacterial infections while being treated with Ig20Gly, and patients were generally satisfied with the treatment. Overall, the CORE study describes how patients with primary immunodeficiency diseases use Ig20Gly in their daily lives, and shows that Ig20Gly treatment can be tailored to suit each patient's needs. Information from this study will help doctors to support patients in making decisions about their treatment.

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease.

OBJECTIVES: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. METHODS: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. RESULTS: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007. CONCLUSION: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.