BACKGROUND: X-linked agammaglobulinemia (XLA), caused by mutations in the Bruton tyrosine kinase (BTK) gene, leads to defective B-cell development and low or absent serum immunoglobulins. Advances in diagnosis and treatment have improved outcomes, allowing some patients to live beyond their sixth decade. OBJECTIVE: To describe the clinical, genetic, treatment, and functional status of XLA patients aged 55 years or older. METHODS: Immunologists provided anonymized, physician-reported clinical and molecular details of XLA patients aged 55 years or older. Patients were categorized as having missense mutations (BTK missense) or non-missense mutations (BTK non-missense). RESULTS: Fifty-seven patients were submitted. Forty-eight were considered for final analysis, including 43 with molecularly confirmed XLA and 5 with a strong clinical history. Persistent respiratory infections were common: 64.6% (upper respiratory tract) and 83.3% (lower respiratory tract). Chronic lung disease (72.9%) and gastrointestinal/hepatic disorders (47.9%) were among the most prevalent complications. Most living patients (80.5%) reported good functional status (Karnofsky scores > 80). Missense variants accounted for 62.8% (n = 27), non-missense variants for 37.2% (n = 16); 5 patients lacked classifiable mutation details. Among 34 patients with BTK expression data, 70.6% had detectable BTK protein, significantly more common in the missense group (83.3% vs 30%; P = .005). The non-missense group had higher mortality, more infections, greater antibiotic use, worse pulmonary function, and lower functional status. CONCLUSIONS: Chronic respiratory complications are common in older XLA patients, although most maintain good functional status. Genetic testing aids prognostication; BTK missense mutations are linked to better outcomes. Further research is needed to address the unique challenges of aging in XLA.

• Keywords
• Agammaglobulinemia, Antibody deficiency, Bruton tyrosine kinase (BTK), Inborn error of immunity (IEI), X-linked agammaglobulinemia (XLA),
• Publication type
• Journal Article MeSH

This report delves into the challenges and potential solutions associated with flexible, customized subcutaneous immunoglobulin (SCIG) infusion regimens for patients with primary antibody deficiency disease (PAD). Advances in the treatment of inborn errors of immunity, particularly PAD, have converted fatal diseases into chronic, complex, long-term conditions that make adherence to treatment a critical issue. Conventional SCIG infusion regimens, while clinically effective, may not always align with the varied lifestyles, changing lifestyles and commitments of patients which can lead to missed doses, diminishing adherence thus posing potential health risks and compromising the overall effectiveness of treatment. For these reasons, it's important to develop flexible infusion regimens tailored to meet individual patient needs. Patient-centric strategies that promote shared decision-making and awareness of patient status not only promote medical efficacy but also enhance the overall patient experience. The authors of this report call attention for a need to shift toward more adaptable and individualized SCIG treatment plans for PAD patients whose needs may change over the long-term course of treatment.

Primary antibody deficiency (PAD) is a condition where the immune system doesn’t work properly, making it hard for the body to fight infections. To stay healthy, people with PAD need regular doses of a medication called immunoglobulin (IgG), which helps strengthen the immune system. This medication can be given in two main ways: through a vein (intravenously, or IVIG) or under the skin (subcutaneously, or SCIG). SCIG has some important benefits. It can be given at home, making it easier for patients to fit treatment into their daily lives. SCIG also causes fewer side effects compared to IVIG. Patients can choose when to take SCIG, making it more flexible and convenient. This article explains how doctors and patients can work together to make SCIG fit into each person’s lifestyle. Flexibility can make treatment less stressful and help patients stick to their treatment plan. One type of SCIG, called SCIG 16.5%, can be taken daily, weekly, every 2 weeks, or multiple times a week as long as the total monthly dose stays the same. Flexible ways to use SCIG are safe and effective and can help people manage their treatment leading to better health over time.

• Keywords
• Cutaquig, Immunoglobulin replacement therapy, patient-centric, primary antibody deficiency disease, shared decision-making, subcutaneous immunoglobulin,
• MeSH
• Precision Medicine MeSH
• Injections, Subcutaneous MeSH
• Humans MeSH
• Immunization, Passive * methods   MeSH
• Patient-Centered Care MeSH
• Primary Immunodeficiency Diseases * therapy   MeSH
• Infusions, Subcutaneous MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

INTRODUCTION: Human immunoglobulin (IG) administered intravenously (IVIG) or subcutaneously (SCIG) is used to prevent infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies. AREAS COVERED: This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5% (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration. EXPERT OPINION: Individualized treatment for PIDD in children is necessary given the different factors that affect administration of SCIG. Variables such as the dose, dosing interval, administration sites, and ancillary equipment can be adjusted to impact the long-term satisfaction with SCIG administration in pediatric patients. The successful work that has been conducted by both professional and patient organizations to increase awareness of PIDD, especially in pediatric patients, is substantial and ongoing. The importance of early diagnosis and treatment in the pediatric patient population cannot be overstated. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.

Human immunoglobulin (IG) is extracted from the plasma of donors as a sterile, purified blood product that is administered intravenously (via a vein [IVIG]) or subcutaneously (under the skin [SCIG]) and is used for a variety of disorders, including the prevention of infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies. This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5% (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration. The importance of early identification of PIDD, especially in pediatric patients, cannot be overstated to ensure prompt treatment. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.

• Keywords
• Cutaquig, pediatric immunodeficiency, primary immunodeficiency disease, subcutaneous administration of immunoglobulin, subcutaneous immunoglobulin,
• MeSH
• Child MeSH
• Immunoglobulin G MeSH
• Immunoglobulins, Intravenous therapeutic use   MeSH
• Humans MeSH
• Drug-Related Side Effects and Adverse Reactions * drug therapy   MeSH
• Infusions, Subcutaneous methods   MeSH
• Immunologic Deficiency Syndromes * drug therapy   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulins, Intravenous MeSH

[This corrects the article DOI: 10.3389/fimmu.2019.00040.].

• Keywords
• SCIG, antibodies, immunoglobulins, infections, infusion site reactions, primary immunodeficiencies,
• Publication type
• Published Erratum MeSH

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.

• Keywords
• long-term safety, primary immunodeficiencies, prospective data, subcutaneous immunoglobulin, tolerability,
• MeSH
• Bacterial Infections * MeSH
• Immunoglobulin G therapeutic use   MeSH
• Immunoglobulins, Intravenous therapeutic use   MeSH
• Humans MeSH
• Prospective Studies MeSH
• Infusions, Subcutaneous MeSH
• Immunologic Deficiency Syndromes * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulins, Intravenous MeSH

Most primary immunodeficiency diseases, and select secondary immunodeficiency diseases, are treated with immunoglobulin (IG) therapy, administered intravenously or subcutaneously (SCIG). The first instance of IG replacement for primary immunodeficiency disease was a 16.5% formulation administered subcutaneously in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG replacement therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.

Plain language summary Primary immunodeficiency diseases, and select secondary immunodeficiency diseases, weaken the immune system, allowing infections and other health problems to occur more easily. Some patients require treatments to boost their immune system, such as immunoglobulin (IG) therapy, which can be either injected via a needle into a vein (intravenously) or inserted underneath the skin (subcutaneously; SCIG). The first instance of IG treatment for primary immunodeficiency disease was a 16.5% SCIG product given in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.

• Keywords
• Cutaquig®, Gammanorm®, primary immunodeficiency disease, subcutaneous administration of immunoglobulin, subcutaneous immunoglobulin,
• MeSH
• Injections, Subcutaneous MeSH
• Immunoglobulins, Intravenous administration & dosage   immunology   therapeutic use   MeSH
• Humans MeSH
• Immunization, Passive methods   MeSH
• Infusions, Subcutaneous MeSH
• Immunologic Deficiency Syndromes drug therapy   immunology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Immunoglobulins, Intravenous MeSH

Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.

• Keywords
• SCIG, antibodies, immunoglobulins, infections, infusion site reactions, primary immunodeficiencies,
• MeSH
• Child MeSH
• Adult MeSH
• Immunoglobulin G administration & dosage   blood   MeSH
• Immunoglobulins, Intravenous administration & dosage   pharmacokinetics   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Immunization, Passive * methods   MeSH
• Child, Preschool MeSH
• Aged MeSH
• Infusions, Subcutaneous MeSH
• Immunologic Deficiency Syndromes drug therapy   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulins, Intravenous MeSH
• Octagam MeSH Browser