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PURPOSE: To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens. METHODS: Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient's weekly dose. RESULTS: For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy. CONCLUSIONS: SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.
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Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Adulto , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Prospectivos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/tratamento farmacológico , Infusões Subcutâneas , Imunoglobulina G/uso terapêutico , Doenças da Imunodeficiência Primária/tratamento farmacológico , Avaliação de Resultados da Assistência ao PacienteRESUMO
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.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Síndromes de Imunodeficiência , Humanos , Criança , Síndromes de Imunodeficiência/tratamento farmacológico , Infusões Subcutâneas/métodos , Imunoglobulina G , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêuticoRESUMO
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.
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Infecções Bacterianas , Síndromes de Imunodeficiência , Humanos , Estudos Prospectivos , Infusões Subcutâneas , Síndromes de Imunodeficiência/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Resultado do Tratamento , Imunoglobulinas Intravenosas/uso terapêuticoRESUMO
PURPOSE: This report calls attention to the potential risks of diminished kidney function when administering immune globulin (IG). The goal is to increase awareness of chronic kidney disease (CKD) and kidney function impairment in patients receiving IG and provide recommendations for screening, monitoring, and management to promote risk prevention and mitigation. SUMMARY: Human IG preparations for intravenous (IVIG) or subcutaneous (SCIG) administration are the mainstay of treatment in patients with primary immunodeficiency diseases. Increasingly, IVIG at high doses (1,000 to 2,400 mg/kg) is also used as a treatment for a variety of autoimmune and inflammatory conditions. Although some autoinflammatory disorders respond to a single course of IVIG therapy, the majority of patients require long-term, regular infusions, thereby increasing the overall risks. Often, both patients and physicians treating adults with IG are unaware of underlying CKD or kidney function impairment. This lack of awareness constitutes a major risk factor for potential worsening, particularly when using high doses of IVIG. Therefore, screening of all patients for CKD and kidney function impairment before the use of IG is essential. Identification of the cause of kidney impairment is strongly encouraged, as IG therapy may need to be modified. CONCLUSION: As detailed here, there are potential risks to patients with impaired kidney function with administration of IG, particularly at high doses. Product selection, volume, route of administration, and rate of infusion may impact those with compromised kidney function. Therefore, screening of all patients for CKD and kidney function impairment before the use of IVIG and SCIG, as well as ongoing monitoring and management, is critical. As with all potential adverse drug reactions, the best approach is to prevent them.
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Síndromes de Imunodeficiência , Insuficiência Renal Crônica , Administração Intravenosa , Adulto , Humanos , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/efeitos adversos , Síndromes de Imunodeficiência/tratamento farmacológico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapiaRESUMO
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.
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Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/imunologia , Infusões Subcutâneas , Injeções Subcutâneas , Resultado do TratamentoRESUMO
[This corrects the article DOI: 10.3389/fimmu.2019.00040.].
RESUMO
Background: Subcutaneous human immunoglobulin (16.5%; octanorm/cutaquig®) was efficacious and well tolerated in patients with primary immunodeficiencies in a Phase III study. A subanalysis of pediatric data is presented here. Materials & methods: Children (2-16 years) previously treated with intravenous human immunoglobulin received weekly subcutaneous human immunoglobulin infusions over 64 weeks. The main objective was to assess the efficacy of cutaquig in preventing serious bacterial infections. Results: 38 children received 2213 infusions of cutaquig. No serious bacterial infections developed during the study. The rate of other infections was 3.1 per person-year and the rate of adverse drug reactions was 0.083 per infusion. Higher immunoglobulin G trough levels were achieved with cutaquig compared with previous intravenous therapy. Conclusion: Once-weekly infusions of cutaquig were efficacious and well tolerated in children with primary immunodeficiencies.
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Imunoglobulinas/uso terapêutico , Doenças da Imunodeficiência Primária/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Infusões Subcutâneas , Masculino , Estudos ProspectivosRESUMO
Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis in children who have an acute manifestation of varied neuropsychiatric symptoms, including obsessive compulsive disorder, eating disorders, tics, anxiety, irritability, and problems with attention/concentration. PANS may develop as a result of a postinfectious syndrome and may represent a new form of postinfectious autoimmunity. To test the hypothesis that multiple, consecutive infusions of intravenous immunoglobulin (IVIG) for PANS can be efficacious, a multisite, open-label study was designed. Methods: The primary endpoint was evaluation of the efficacy of IVIG [Octagam 5%] in PANS over a period of 6 months (six infusions) based on mean changes in psychological evaluation scores using 6 different assessments, including the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Clinical Global Impression of Severity, and the Parent-Rated Pediatric Acute Neuropsychiatric Symptom Scale (PANS Scale). Results: The final cohort consisted of 21 subjects (7 per site) with moderate to severe PANS. The mean age was 10.86 years (range: 4-16 years). Results demonstrated statistically significant reductions in symptoms from baseline to end of treatment in all six assessments measured. CY-BOCS results demonstrated statistically significant reductions in obsessive compulsive symptoms (p < 0.0001), resulting in >50% improvement sustained for at least 8 weeks after the final infusion and up to 46 weeks in a subset of subjects. Conclusions: In PANS, which may be associated with an underlying immune dysregulation, sequential infusions of IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks in a subset of subjects. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.
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Doenças Autoimunes/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Resultado do Tratamento , Ansiedade , Criança , Estudos de Coortes , Transtornos da Alimentação e da Ingestão de Alimentos , Feminino , Humanos , Masculino , Infecções Estreptocócicas/diagnósticoRESUMO
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.
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Imunização Passiva , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imunização Passiva/métodos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacocinética , Imunoglobulinas Intravenosas/uso terapêutico , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: To assess the safety and efficacy of an intravenous immunoglobulin (IVIG) 10% preparation (Panzyga®; Octapharma AG, Lachen, Switzerland) in predominantly antibody-deficient children with primary immunodeficiency disease. METHODS: Data from two prospective, open-label and noncontrolled multicenter Phase III studies of IVIG 10% that included 25 patients <16 years of age were analyzed for efficacy, pharmacokinetics and safety. RESULTS: The rate of serious bacterial infections was 0.04/patient-year. A maximal infusion rate of 0.14 ml/kg/min was achieved in 82% of pediatric patients (n = 9). Infusions of immunoglobulin G trough levels between infusions remained ≥5-6 g/l; median half-life was 32.79-36.62 days. Abdominal pain, headache and chills were the most common treatment-related adverse events. CONCLUSION: IVIG 10% is safe and effective for the treatment of predominantly antibody-deficient children.
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Agamaglobulinemia/terapia , Infecções Bacterianas/epidemiologia , Imunodeficiência de Variável Comum/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Adolescente , Adulto , Agamaglobulinemia/epidemiologia , Idoso , Infecções Bacterianas/etiologia , Criança , Imunodeficiência de Variável Comum/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Background: New sequencing techniques have revolutionized the identification of the molecular basis of primary immunodeficiency disorders (PID) not only by establishing a gene-based diagnosis but also by facilitating defect-specific treatment strategies, improving quality of life and survival, and allowing factual genetic counseling. Because these techniques are generally not available for physicians and their patients residing in developing countries, collaboration with overseas laboratories has been explored as a possible, albeit cumbersome, strategy. To reduce the cost of time and temperature-sensitive shipping, we selected Guthrie cards, developed for newborn screening, to collect dried blood spots (DBS), as a source of DNA that can be shipped by regular mail at minimal cost. Method: Blood was collected and blotted onto the filter paper of Guthrie cards by completely filling three circles. We enrolled 20 male patients with presumptive X-linked agammaglobulinemia (XLA) cared for at the Vietnam National Children's Hospital, their mothers, and several sisters for carrier analysis. DBS were stored at room temperature until ready to be shipped together, using an appropriately sized envelope, to a CLIA-certified laboratory in the US for sequencing. The protocol for Sanger sequencing was modified to account for the reduced quantity of gDNA extracted from DBS. Result: High-quality gDNA could be extracted from every specimen. Bruton tyrosine kinase (BTK) mutations were identified in 17 of 20 patients studied, confirming the diagnosis of XLA in 85% of the study cohort. Type and location of the mutations were similar to those reported in previous reviews. The mean age when XLA was suspected clinically was 4.6 years, similar to that reported by Western countries. Two of 15 mothers, each with an affected boy, had a normal BTK sequence, suggesting gonadal mosaicism. Conclusion: DBS collected on Guthrie cards can be shipped inexpensively by airmail across continents, providing sufficient high-quality gDNA for Sanger sequencing overseas. By using this method of collecting gDNA, we were able to confirm the diagnosis of XLA in 17 of 20 Vietnamese patients with the clinical diagnosis of agammaglobulinemia.
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Agamaglobulinemia/diagnóstico , Coleta de Amostras Sanguíneas/métodos , DNA/análise , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Triagem Neonatal/métodos , Manejo de Espécimes/métodos , Adulto , Agamaglobulinemia/genética , Coleta de Amostras Sanguíneas/instrumentação , Criança , Pré-Escolar , Análise Mutacional de DNA/instrumentação , Análise Mutacional de DNA/métodos , Países em Desenvolvimento , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/instrumentação , Fenótipo , VietnãRESUMO
Intravenous immunoglobulin (IVIG) therapy is commonly used to treat patients with primary antibody deficiency. This prospective, open-label, non-randomised, multicentre, phase III trial investigated the pharmacokinetics of a new 10% liquid IVIG product (panzyga®; Octapharma) in 51 patients aged 2-75â¯years with common variable immunodeficiency (nâ¯=â¯43) or X-linked agammaglobulinaemia (nâ¯=â¯8). Patients were treated with IVIG 10% every 3 (nâ¯=â¯21) or 4â¯weeks (nâ¯=â¯30) at a dose of 200-800â¯mg/kg for 12â¯months. Total immunoglobulin G (IgG) and subclass concentrations approximately doubled from pre- to 15â¯min post-infusion. The maximum concentration of total IgG (mean⯱â¯SD) was 21.82⯱â¯5.83â¯g/L in patients treated 3-weekly and 17.42⯱â¯3.34â¯g/L in patients treated 4-weekly. Median trough IgG concentrations were nearly constant over the course of the study, remaining between 11.0 and 12.2â¯g/L for patients on the 3-week schedule and between 8.10 and 8.65â¯g/L for patients on the 4-week schedule. The median terminal half-life of total IgG was 36.1 (range 18.5-65.9) days, with generally similar values for the IgG subclasses (26.7-38.0â¯days). Median half-lives for specific antibodies ranged between 21.3 and 51.2â¯days for anti-cytomegalovirus, anti-Haemophilus influenzae, anti-measles, anti-tetanus toxoid, anti-varicella zoster virus antibodies, and anti-Streptococcus pneumoniae subtype antibodies. Overall, IVIG 10% demonstrated pharmacokinetic properties similar to those of other commercial IVIG 10% preparations and 3- or 4-weekly administration achieved sufficient concentrations of IgG, IgG subclasses, and specific antibodies, exceeding the recommended level needed to effectively prevent serious bacterial infections.
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Agamaglobulinemia/metabolismo , Imunodeficiência de Variável Comum/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Imunoglobulinas Intravenosas/farmacocinética , Adolescente , Adulto , Agamaglobulinemia/sangue , Idoso , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/sangue , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/sangue , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (eHCF + LGG; Nutramigen LGG) compared with an eHCF alone and an amino acid formula (AAF) in treating cow's milk allergy (CMA) in the US, from the perspective of third-party insurers and from parents. METHODS: A decision model was used to estimate the probability of cow's milk allergic infants developing tolerance to cow's milk by 18 months. The model also estimated the cost to insurers and parents (US dollars at 2016 prices) of managing infants over 18 months after starting one of the formulae, as well as the relative cost-effectiveness of each of the formulae. RESULTS: The probability of developing tolerance to cow's milk was higher among infants who were fed eHCF + LGG compared with those fed an eHCF alone or an AAF. Infants who are initially fed with eHCF + LGG are expected to utilize fewer healthcare resources than those fed with one of the other formulae. Hence, the estimated total healthcare cost incurred by third-party insurers and parents of initially feeding infants with eHCF + LGG was less than that of feeding infants with an eHCF alone or an AAF. CONCLUSION: Initial management of newly-diagnosed cow's milk allergic infants with eHCF + LGG was found to afford a cost-effective strategy to both third-party insurers and parents when compared to an eHCF alone or an AAF.
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Caseínas , Fórmulas Infantis/economia , Lacticaseibacillus rhamnosus/fisiologia , Hipersensibilidade a Leite , Probióticos/uso terapêutico , Caseínas/economia , Caseínas/uso terapêutico , Quelantes , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Humanos , Lactente , Masculino , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/economia , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/terapia , Estados Unidos/epidemiologiaRESUMO
PURPOSE: To assess the efficacy and safety of panzyga® (intravenous immunoglobulin 10%) in preventing serious bacterial infections (SBIs) in patients with primary immunodeficiency diseases (PIDs), a prospective, open-label, multicenter, phase 3 study and an open-label extension study were undertaken. METHODS: Initially, the study drug (infusion rate ≤0.08 mL/kg/min) was administered at intervals of 3 or 4 weeks for 12 months, followed by 3 months of panzyga® at infusion rates increasing from 0.08 to 0.14 mL/kg/min. The primary endpoint in the main study was the rate of SBIs per patient-year on treatment. Secondary outcomes included non-serious infections, work/school absence, episodes of fever, quality of life, and adverse events (AEs). RESULTS: The main study enrolled 51 patients (35% female, mean age 26.8 years), with 21 participating in the extension study. The rate of SBIs per patient-year was 0.08 in the total population; there were four SBIs in the 4-weekly treatment group (2/30 patients) and none in the 3-weekly group (n = 21). Compared with 4-weekly treatment, 3-weekly treatment was associated with a higher rate of upper respiratory tract infections (RTIs), ear infections, and work/school absences, but a lower rate of lower RTIs and fever. Treatment was generally well tolerated; no AE led to treatment withdrawal or death. CONCLUSIONS: Overall, the use of panzyga® in patients with antibody-deficient PID was associated with a low rate of AEs and was effective in preventing SBIs, exceeding US FDA and European Medicines Agency recommendations for efficacy.
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Infecções Bacterianas/terapia , Imunoglobulina G/uso terapêutico , Imunoglobulinas/deficiência , Síndromes de Imunodeficiência/terapia , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Adolescente , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV). METHODS: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD. RESULTS: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year. CONCLUSIONS: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.
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Imunoglobulinas Intravenosas/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. We present a case of a 69-year-old man with maxillary sinus IgG4 sclerosing disease, with orbital invasion treated with rituximab and dexamethasone pulse therapy. Surgery was used as well to debulk the disease and to obtain tissue for diagnosis. METHODS: A PubMed search using the key phrase "IgG4-related Sclerosing Disease" was performed. There were 304 different articles regarding the disease for a multitude of different organ sites. Of the 304 articles, there were 3 articles that reported this disease in the paranasal sinuses. CONCLUSIONS: IgG4-related sclerosing disease is a rare entity in the head and neck. There are documented reports of steroid therapy for this disease, but the patient presented here demonstrated clinical progression of disease with steroids alone. The use of combination therapy of surgery, dexamethasone, and rituximab provided clinical improvement and stable disease determined by radiographic means.