Intravenous immunoglobulin 10% in children with primary immunodeficiency diseases.

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.

Pharmacokinetics of a novel human intravenous immunoglobulin 10% in patients with primary immunodeficiency diseases: Analysis of a phase III, multicentre, prospective, open-label study.

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 2-75 years with common variable immunodeficiency (n = 43) or X-linked agammaglobulinaemia (n = 8). Patients were treated with IVIG 10% every 3 (n = 21) or 4 weeks (n = 30) at a dose of 200-800 mg/kg for 12 months. Total immunoglobulin G (IgG) and subclass concentrations approximately doubled from pre- to 15 min post-infusion. The maximum concentration of total IgG (mean ±â€¯SD) was 21.82 ±â€¯5.83 g/L in patients treated 3-weekly and 17.42 ±â€¯3.34 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 12.2 g/L for patients on the 3-week schedule and between 8.10 and 8.65 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 (26.7-38.0 days). Median half-lives for specific antibodies ranged between 21.3 and 51.2 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.

Efficacy and Safety of Human Intravenous Immunoglobulin 10% (Panzyga®) in Patients with Primary Immunodeficiency Diseases: a Two-Stage, Multicenter, Prospective, Open-Label Study.

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.

Flebogamma(®) 5 % DIF Intravenous Immunoglobulin for Replacement Therapy in Children with Primary Immunodeficiency Diseases.

PURPOSE: The previous studies with Flebogamma(®) 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5 % DIF for replacement therapy in children (age 2-16) with primary immunodeficiency diseases (PIDD). METHODS: IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300-800 mg/kg every 21-28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels. RESULTS: The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of <40 % at each time point. Dose-adjusted incremental IgG levels remained approximately equal to or slightly greater than pre-study IgG levels (between 800 and 1000 mg/dL throughout) when the subjects were treated with IVIG therapy other than Flebogamma(®) DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations. CONCLUSIONS: Flebogamma(®) 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma(®) 5 % for the treatment of children with primary humoral immunodeficiency diseases.

Managing difficult-to-treat asthma: Lessons from a center of excellence in allergy and asthma care.

One in four asthma patients may not have their condition adequately controlled despite being treated according to current practice guidelines, and these patients experience persistent symptoms, frequent exacerbations, and high healthcare utilization. The Allergy and Asthma Center, a recognized center of excellence in the treatment of allergy and asthma, is based on a patient-first philosophy, and this article explains how the practice operates and the importance of maintaining efficient office flow, implementing technology, and building a caring and dedicated staff Because asthma patients are often referred from primary care physicians, many present with difficult-to-treat disease. Even though many of these patients have received inhaled corticosteroids either alone or in combination with other medications, their condition still remains not well controlled. Serum total immunoglobulin E (IgE) is commonly elevated in patients with dfficult-to-treat asthma, and consequently, the IgE blocker omalizumab may be a viable option in this setting.

Safety of rush immunotherapy using a modified schedule: a cumulative experience of 893 patients receiving multiple aeroallergens.

Conventional immunotherapy (IT) is effective in treating allergic rhinitis, allergic asthma, and chronic rhinosinusitis. Disadvantages include poor compliance, delayed efficacy, and patient frustration. Rush IT, or rapid desensitization, offers the advantages of rapid response, improved compliance, and cost-effectiveness. Although premedication with corticosteroids and antihistamines dramatically reduces systemic reactions, safety remains a primary concern. Two separate half-day schedules with minor differences were used to rapidly desensitize 893 patients (aged 1.5-77 years) in two typical outpatient settings equipped to treat anaphylaxis. All patients exhibited positive skin-prick tests to perennial and seasonal allergens. Diagnoses included allergic rhinitis (857/96%), allergic asthma (505/57%), and chronic rhinosinusitis (384/43%). Five hundred sixty-eight patients were premedicated with prednisone and HI-antihistamine for 3 days. Three hundred twenty-five patients were premedicated for 3 days with prednisone and H1- and H2-blockade. The protocol's final dose ranged from 0.1 to 0.5 mL of a 1:1000 dilution of extracts manufactured by ALK and Greer Laboratories. Patients continued on to higher doses by resuming a conventional schedule. Eighteen patients (2.0%) experienced a mild systemic reaction. All responded to subcutaneous epinephrine and/or nebulized albuterol and were sent home after observation. One patient (0.1%) experienced true anaphylaxis and received appropriate treatment and observation. Our experience with rush IT confirms that maintenance IT can be reached quickly and safely under careful supervision. Caution must be exercised when using this procedure because anaphylaxis does occur. Systemic reactions occur less frequently using a lower targeted final dose than previously described in the literature.

Improved immunotherapy with a rapid allergen vaccination schedule: a study of 137 patients.

Rapid allergen vaccination (RAV) is the updated term for what was previously called rush immunotherapy and rapid desensitization. RAV offers several advantages over traditional immunotherapy--that is, conventional allergen vaccination (CAV)--in terms of faster efficacy, better compliance, and cost-effectiveness. We used a 3-hour RAV protocol to treat 137 allergy patients. All patients were premedicated with either prednisone or prednisolone and an H1 antihistamine. Following the RAV procedure, all patients resumed a CAV schedule. Only six patients (4.4%) experienced a mild systemic reaction to RAV, and five (3.6%) experienced a mild systemic reaction to CAV 14 to 77 days later. All six patients who reacted to RAV quickly responded to treatment--in most cases, subcutaneous epinephrine and/or nebulized albuterol--and were sent home after a short period of observation. Compliance rates at 3, 6, and 12 months were 96.4, 94.2, and 75.9%, respectively, which is an improvement over rates previously reported for patients undergoing CAV therapy. We conclude that the 3-hour RAV protocol can be safely and successfully administered. Patients who undergo RAV are more compliant with their subsequent CAV regimen than are patients who do not undergo RAV because signs of clinical efficacy manifest almost immediately and because RAV is associated with substantially lower rates of systemic reactions. Moreover, RAV is associated with less morbidity and less expense. Our findings should encourage physicians who treat allergy patients to give further consideration to using RAV.

Evaluating the response of patients undergoing both allergy skin testing and in vitro allergy testing with the ImmunoCAP Technology System.

PURPOSE: To evaluate the response of patients who underwent both skin and in vitro allergy testing, both of which are accepted methods. DATA SOURCES: Retrospective review of the case notes of 100 patients evaluated by both testing methods for allergic disease. CONCLUSIONS: A total of 62 patients (62%) tested positive to at least one of the tested allergens via the in vitro method. A total of 65 patients (65%) tested positive to at least one allergen via the skin-testing method. The most frequently elicited allergic response from the in vitro method was to white oak. Indoor mold and dust most frequently elicited response via skin testing. IMPLICATIONS FOR PRACTICE: Both in vitro and in vivo allergy testing have limitations. Practitioners should be aware of these when establishing a treatment plan based on the results of differing allergy testing methods. Due to differing responses to skin and in vitro testing methods, it may be prudent to perform both tests to obtain a definitive diagnosis for the allergic patient.