Liquid Intravenous Immunoglobulin Research Articles

Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: Results of the ProCID Study.

The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga®) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings. Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks. All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64-90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication. Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP. EudraCT 2015-005443-14, NCT02638207.

Randomized trial of three IVIg doses for treating chronic inflammatory demyelinating polyneuropathy

Intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy usually starts with a 2.0 g/kg induction dose followed by 1.0 g/kg maintenance doses every 3 weeks. No dose-ranging studies with intravenous immunoglobulin maintenance therapy have been published.The Progress in Chronic Inflammatory Demyelinating polyneuropathy (ProCID) study was a prospective, double-blind, randomized, parallel-group, multicentre, phase III study investigating the efficacy and safety of 10% liquid intravenous immunoglobulin (Panzyga®) in patients with active chronic inflammatory demyelinating polyneuropathy. Patients were randomized 1:2:1 to receive the standard intravenous immunoglobulin induction dose and then either 0.5, 1.0 or 2.0 g/kg maintenance doses every 3 weeks. The primary end point was the response rate in the 1.0 g/kg group, defined as an improvement ≥1 point in adjusted Inflammatory Neuropathy Cause and Treatment score at Week 6 versus baseline and maintained at Week 24. Secondary end points included dose response and safety. This trial was registered with EudraCT (Number 2015–005443-14) and clinicaltrials.gov (NCT02638207).Between August 2017 and September 2019, the study enrolled 142 patients. All 142 were included in the safety analyses. As no post-infusion data were available for three patients, 139 were included in the efficacy analyses, of whom 121 were previously on corticosteroids. The response rate was 80% (55/69 patients) [95% confidence interval (CI): 69–88%] in the 1.0 g/kg group, 65% (22/34; CI: 48–79%) in the 0.5 g/kg group, and 92% (33/36; CI: 78–97%) in the 2.0 g/kg group. While the proportion of responders was higher with higher maintenance doses, logistic regression analysis showed that the effect on response rate was driven by a significant difference between the 0.5 and 2.0 g/kg groups, whereas the response rates in the 0.5 and 2.0 g/kg groups did not differ significantly from the 1.0 g/kg group. Fifty-six per cent of all patients had an adjusted Inflammatory Neuropathy Cause and Treatment score improvement 3 weeks after the induction dose alone. Treatment-related adverse events were reported in 16 (45.7%), 32 (46.4%) and 20 (52.6%) patients in the 0.5, 1.0 and 2.0 g/kg dose groups, respectively. The most common adverse reaction was headache. There were no treatment-related deaths.Intravenous immunoglobulin (1.0 g/kg) was efficacious and well tolerated as maintenance treatment for patients with chronic inflammatory demyelinating polyneuropathy. Further studies of different maintenance doses of intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy are warranted.

Efficacy, Safety and Tolerability of a New 10% Intravenous Immunoglobulin for the Treatment of Primary Immunodeficiencies

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov: NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency.

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 ± SD) was 21.82 ± 5.83 g/L in patients treated 3-weekly and 17.42 ± 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.

Validation and implementation of Planova™ BioEX virus filters in the manufacture of a new liquid intravenous immunoglobulin in China

There is a continuous need to improve the viral safety of plasma products, and we here report the development and optimization of a manufacturing-scale virus removal nanofiltration step for intravenous immunoglobulin (IVIG) using the recently introduced Planova™ BioEX filter. IVIG throughput was examined for various operating parameters: transmembrane pressure, temperature, protein concentration, and prefiltration methods. The developed procedure was based on filtering undiluted process solution (50.0 g/l IVIG) under constant transmembrane pressure filtration at 294 kPa and 25 °C following prefiltration with a 0.1 μm MILLEX VV filter. The recovery of IgG was approximately 98%, and no substantial changes in biochemical characteristics were observed before and after nanofiltration in scaled-up production. A viral clearance validation study with parvovirus under worst-case conditions performed at the National Institutes for Food and Drug Control of China (NIFDC) showed PPV logarithmic reduction value (LRV) > 4. Improved viral safety of IVIG can be assured by implementing a Planova BioEX nanofiltration step to ensure effective parvovirus clearance under conditions providing excellent protein recovery and no detectable impact on product biochemical properties. This plasma-derived IVIG product is the first to be certified for parvovirus safety by the NIFDC in China.

Cost-Minimization Analysis of 10% Intravenous Immunoglobulin In Treatment Of Primary Immunodeficiencies In Children In The Russian Federation

To conduct cost-minimization analysis of 10% liquid intravenous immunoglobulin (IVIG) compared with IVIGs of 5% concentration in treatment of primary immunodeficiencies (PID) in children in Russia for 1-year period. A cost-minimization model was developed in Excel 2013 to simulate the direct and indirect costs for 1-year period. Costs included ones for treatment course with IVIGs and IVIG administration, expenditures of infections' treatment, ones associated with storage and transportation of IVIG, disability pensions and payment for sick leave in connection with caring for a sick child. The following sources were used for calculations: epidemiological data from Ministry of health reports, database of tenders for purchase of medicines, prescribing Information for the drugs, Federal statistical monitoring in the sphere of payment of labour of social workers, tariffs for payment of medical care in stationary conditions on completed cases, requirements of sanitary-epidemiological rules, wholesale prices on refrigerated equipment, the duration of the absence of children in educational institution because of PID according to Stein et al.,2009. According to the cost-minimization analysis, 10% IVIG (Switzerland) therapy (552,618 rubles/9,690 $) is the least costly by the end of the 1 year per 1 patient. Therapy with 5% IVIG (Italy) costs 621,567 rubles/10 899 $, 5% IVIG (Austria) and 5% IVIG (Germany) cost 618,223 rubles/10,840 $ and 736,243 rubles/12,910 $ consequently. Current rate taken as for 15.06.2017 is 1$ = 57,03 RUB. The treatment of primary immunodeficiencies with 10% liquid intravenous immunoglobulin (Switzerland) is a cost saving option compared with treatment with 5% IVIGs in children in Russia for 1-year period.

A Multicentre Study on the Efficacy, Safety and Pharmacokinetics of IqYmune\xae, a Highly Purified 10% Liquid Intravenous Immunoglobulin, in Patients with Primary Immune Deficiency

This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2–61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.

Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma.

BackgroundA highly purified 10% liquid intravenous immunoglobulin, IQYMUNE®, has been developed using an innovative manufacturing process including an affinity chromatography step for the removal of anti-A and anti-B hemagglutinins.ObjectivesThe pathogen (viruses and prions) clearance efficacy of the manufacturing process and its robustness for critical steps were investigated.MethodsThe manufacturing process of IQYMUNE® includes two dedicated complementary virus reduction steps: solvent/detergent (S/D) treatment and 20 nm nanofiltration as well as two contributing steps, namely caprylic acid fractionation and anion-exchange chromatography. The clearance capacity and robustness of these steps were evaluated with a wide range of viruses (enveloped and non-enveloped) and with a model of human transmissible spongiform encephalopathies (TSEs).ResultsThe IQYMUNE® manufacturing process demonstrated a high and robust virus removal capacity with global reduction factors (RFs) of relevant and model viruses: ≥14.8 log10 for human immunodeficiency virus type 1 (HIV-1), ≥16.9 log10 for bovine viral diarrhoea virus (BVDV)/Sindbis virus, ≥15.7 log10 for pseudorabies virus (PRV), ≥12.8 log10 for encephalomyocarditis virus (EMCV) and 11.0 log10 for porcine parvovirus (PPV). The process also exhibited a high removal capacity for the TSE agent with an overall RF of ≥12.9 log10 due to the complementary actions of the caprylic acid fractionation, anion-exchange chromatography and nanofiltration steps.ConclusionData from virus and prion clearance studies fully support the high safety profile of IQYMUNE®, with a minimal reduction of 11 log10 for the smallest and most resistant non-enveloped virus, PPV, and more than 12 log10 for the TSE agent.

Demonstration of safety of intravenous immunoglobulin in geriatric patients in a long-term, placebo-controlled study of Alzheimer's disease

IntroductionWe present safety results from a study of Gammagard Liquid intravenous immunoglobulin (IGIV) in patients with probable Alzheimer's disease. MethodsThis was a placebo-controlled double-blind study. Subjects were randomized to 400 mg/kg (n = 127), 200 mg/kg (n = 135) IGIV, or to 0.25% human albumin (n = 121) administered every 2 weeks ± 7 days for 18 months. ResultsElevated risk ratios of IGIV versus placebo included chills (3.85) in 9.5% of IGIV-treated subjects (all doses), compared to 2.5% of placebo-treated subjects, and rash (3.08) in 15.3% of IGIV-treated subjects versus 5.0% of subjects treated with placebo. Subjects in the highest IGIV dose group had the lowest proportion of SAEs considered related to product (2 of 127 [1.6%]). Subjects treated with IGIV experienced a lower rate of respiratory and all other infections compared to placebo. DiscussionIGIV-treated subjects did not experience higher rates of renal failure, lung injury, or thrombotic events than the placebo group. There were no unexpected safety findings. IGIV was well tolerated throughout 18 months of treatment in subjects aged 50–89 years.

Development of an intravenous immunoglobulin with improved safety and functional activity

The development and properties of a liquid intravenous immunoglobulin (Gammaplex®), of high purity, stability and functional activity, is described. Virus and TSE reduction by specific steps in the process were evaluated by spiking studies using small-scale models. The removal of procoagulant activity was determined using immunochemical and functional activity assays. Neutralisation and opsonic activity were used to demonstrate the functional activity of the IgG. The final low pH formulated product was stable at room temperature and was of high purity and functional activity. Three dedicated virus inactivation steps, i.e. solvent detergent, low pH and virus filtration, were shown to be effective. When combined with the B + I ethanol precipitation step, this gave a total reduction of >21 to >24 log for the enveloped and >10 to >13 log for the non-enveloped viruses tested. Several steps in the process were shown to contribute to TSE removal using scrapie. Potential procoagulant activity including Factor XI/XIa, was reduced to very low/undetectable levels in the final product. A new high purity liquid IVIG product has been developed, of high purity and good functional activity and stability. The process includes various steps for the removal of pathogens and procoagulant activity.

Isoagglutinin Reduction in Human Immunoglobulin Products by Donor Screening.

IntroductionHemolysis is considered a class effect and a rare adverse event that can occur following therapy with human normal immunoglobulin for intravenous administration [i.e., intravenous immunoglobulin (IVIG)]. Anti-A/B isoagglutinins (also referred to as isohemagglutinins) originating from donor plasma are present in polyvalent immunoglobulin G (IgG) products and are considered a probable risk factor for hemolysis. We hypothesized that, by excluding plasma from donors with high isoagglutinin titers, the final IVIG product would have a meaningful reduction in anti-A/B isoagglutinin titers.MethodsA method for screening donor plasma for anti-A isoagglutinins using an automated indirect agglutination test (IAT) was developed. A cut-off for donor plasma exclusion was defined. Industry-scale donor plasma pools and final IVIG product were prepared according to the manufacturing process of Privigen® (CSL Behring, Berne, Switzerland; human 10% liquid IVIG). Anti-A/B isoagglutinin content in pooled plasma and final IVIG product was measured by IAT, direct agglutination test, and a flow cytometry-based assay [fluorescence-activated cell sorting (FACS) anti-A].ResultsScreening of plasma from 705 donors identified 48 (6.8%) donors with high anti-A isoagglutinin titers in plasma (IAT agglutination score ≥2+ in a 1:200 pre-dilution). Exclusion of plasma from these donors resulted in a one-titer-step reduction of anti-A isoagglutinin in pooled plasma, confirmed by a twofold anti-A isoagglutinin concentration reduction measured by FACS anti-A (1,352 vs. 2,467 µg/g IgG). When the same screening and exclusion were applied to industrial-scale plasma pools (resulting in the exclusion of plasma from 5% of donors), anti-A isoagglutinins were reduced by one titer step in the final IVIG product. Anti-B isoagglutinins were also reduced by one titer step, as many donors with high anti-A isoagglutinins also have high anti-B.ConclusionReduction of anti-A/B isoagglutinin titers in IVIG products on an industrial scale is feasible through implementation of anti-A donor screening, which may reduce the risk of hemolysis following IVIG therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s13554-014-0016-2) contains supplementary material, which is available to authorized users.

High-Dose Intravenous Immunoglobulin (IVIG) Adjuvant Therapy for Cell-Mediated Pancreas Transplant Rejection

High-Dose Intravenous Immunoglobulin (IVIG) Adjuvant Therapy for Cell-Mediated Pancreas Transplant Rejection

A Phase III, Randomized, Placebo-Controlled Study of the Efficacy and Safety of 10% Liquid Intravenous Immunoglobulin (IGIV) for the Treatment of Multifocal Motor Neuropathy (MMN)

tube irritation during daily activities such as suction, transfer. Patient 2 showed reflex cough and abnormal posturing due to tube irritation. They underwent granulation removal and stomaplasty for making permanent tracheostoma after 60, 22, 12 months of the first conventional tracheostomy. Setting: Tertiary care hospital Results or Clinical Course: For all three patients, no early and late complications occurred, and airway patency was well maintained. Frequency of suction, sudden spasticity increase, reflex cough were reduced, and airway hygiene was improved after the permanent tracheostoma. All three caregivers reported the reduced difficulty and anxiety and also their satisfaction after the procedure. Discussion: Permanent tracheostoma establishes a short, skinlined, noncollapsing, nonstenosing, self-sustaining passage between the trachea and the external environment, and is not supported by a tube, vent, or stent. The benefit of this tube-free, permanent tracheostoma is that the patients are free of risk for complication caused by tracheostomy tube itself, such as tube displacement, tube obstruction, granuloma, tracheal stenosis. This method is a useful alternative way to make long-term ventilatory bypass without tuberelated complications in the chronic disease such as obstructive sleep apnea, bilateral vocal cord paralysis, laryngotracheal stenosis, chronic pulmonary disease, laryngeal cancer. It is the first report of successful permanent tracheostoma in chronic brain injured patients with long-term tracheostomy, who had cognitive deficit, and weakness of four extremities, and poor head and neck control due to their quadriplegic status. Conclusions: Permanent tracheostoma can be considered a useful alternative way for chronic brain injured patients with long-term tracheostomy.

A 10% liquid immunoglobulin preparation for intravenous use (Privigen®) in paediatric patients with primary immunodeficiencies and hypersensitivity to IVIG

BackgroundThe objective of this study was to evaluate safety and efficacy of Privigen®, a 10% intravenous immunoglobulin (IVIG), in a particular group of paediatric patients (highly sensitive to previous IVIG infusion) affected with Primary Immunodeficiencies (PID). Material and methodsPatients (n=8) from 3 to 17 years old diagnosed of PID who often suffered from adverse events related to the infusion to previous IVIG were switched to Privigen® in an open protocol. Data were prospectively collected regarding Privigen® administration: infusion, safety and efficacy. In parallel, data on safety and tolerance were retrospectively collected from medical charts regarding the previous 10% IVIG product used. Results50% of the patients required premedication with previous IVIG. At the end of the study none required premedication with Privigen®. The infusion rate was lower than that recommended by the manufacturer. All patients had suffered through adverse events during previous IVIG infusion being severe in three patients and recurrent in the rest. With Privigen® only three patients suffered from an adverse event (all cases were milder than previous related). Trough levels of IgG remained stable. None suffer from any episode of bacterial infection. ConclusionThe present work shows that Privigen® was safe in a group of hypersensitive paediatric patients who did not tolerate the administration of a previous 10% liquid IVIG by using a particular infusion protocol slower than recommended. The number of adverse effects was smaller than published, and all cases were mild. No premedication was needed. Privigen® was also effective in this small group.

In vitro and in vivo properties differ among liquid intravenous immunoglobulin preparations

Objective To compare in vitro and in vivo biological and biochemical properties of five liquid intravenous immunoglobulin (IVIg) preparations licensed for therapeutic use in Europe.Methods ClairYg® was compared in a blinded manner to four other liquid IVIg preparations licensed in Europe (Octagam®, Kiovig®, Gamunex®, Privigen®). Three batches of each preparation were tested, except for the IgG repertoires and the animal model.Results Levels of anti-A and anti-B antibodies were lower in ClairYg® (0·11/0·11) relative to a positive EDQM standard and Octagam® (0·11/0·08) than in other preparations (0·33–0·69/0·42–0·46). IgG in ClairYg® recognized 365 and 416 protein spots in HEp-2 cell and Escherichia coli protein extracts vs. 230–330 and 402–842 protein spots, respectively, for IgG in other preparations. IgA content (301 vs. 165–820 ng/mg of IgG), Factor XI and Factor XII antigen (0·46 vs. 0·85–2·40 mU/mg of IgG and 7·8 vs. 20·0–46·2 lU/mg of IgG) C1q binding (0·42 vs. 0·67–1·89 arbitrary units) and C5a uptake (0·41 vs. 0·45–0·66% of activation) were lower in ClairYg® than in other preparations. Finally, intravenous infusion of ClairYg®, Gamunex® and Privigen® had no major effect on arterial blood pressure in spontaneously hypertensive rats.Conclusions Our results evidence some differences in the biological and biochemical properties among licensed liquid IVIg preparations.

Safety, Efficacy and Pharmacokinetics of a New 10% Liquid Intravenous Immunoglobulin (IVIG) in Patients with Primary Immunodeficiency

IntroductionAn investigational 10% liquid intravenous immunoglobulin (IVIG) was studied in 63 patients with primary immunodeficiency (PID) at 15 study sites.MethodsPatients were treated every 3 or 4 weeks with 254–1029 mg/kg/infusion of IVIG.ResultsOverall, Biotest-IVIG infusions were well tolerated. The proportion of infusions that were associated with adverse events during infusion, and up to 72 h after infusion, including those unrelated to study product, was 27.7% with an upper 95% confidence limit ≤30.6%. Two serious bacterial infections (SBIs) were observed resulting in a serious bacterial infection rate of 0.035 per person per year and an upper one-sided 99% confidence limit of ≤0.136 SBI/patient/year. The number of days of work or school missed due to infection were relatively low at 2.28 days/patient/year. Two patients were hospitalized for infection producing a rate of 0.21 hospitalization days/patient/year. The IgG half-life was approximately 30 days with variation among individuals.ConclusionsPharmacokinetic parameters of specific antibody activities were essentially the same as those of total IgG. Biotest-IVIG is safe and effective in the treatment of PID.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies

Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Comparison of Intravenous Immunoglobulin Formulations: Product Formulary, and Cost Considerations

Purpose A review of the different formulations of intravenous immunoglobulin (IVIG) replacement therapy for primary immunodeficiency and other severe diseases, focusing on the comparative efficacy, safety, and tolerability of these formulations. This review discusses the manufacturing processes, physicochemical properties, and other attributes of IVIG therapy that affect its clinical utility. Summary IVIG therapy is a preferred treatment for patients with certain types of primary immunodeficiency, neuroimmunologic, and autoimmune hematologic disorders, as well as for immunomodulation in bone marrow and some solid organ transplants. The IVIG products available in the United States include lyophilized, 5% liquid, and 10% ready-to-use liquid formulations. Differences among these formulations in their manufacturing processes, excipients, pH, and physicochemical properties may be reflected as differences in clinical efficacy, safety, and tolerability. For example, compared with lyophilized and 5% liquid IVIG formulations, 10% ready-to-use IVIG liquid formulations may be associated with better tolerability because of lower IgA concentrations, optimal pH, use of glycine or proline stabilizers, low sodium content, and less osmolality. Liquid formulations (both 5% and 10%) may provide greater convenience than lyophilized formulations for both patients and health care providers, because they do not require further dilution before administration and have shorter infusion times. Conclusion Before selecting an IVIG product for a hospital formulary, pharmacists should be knowledgeable about the product's concentration to ensure delivery of the proper dosage, the staff training needed for proper administration, the potential benefits and problems of brand substitution, the safety and efficacy of each formulation, the hospital's policies on off-label use of IVIG, and the impact of reimbursement.

Efficacy and safety of a nanofiltered liquid intravenous immunoglobulin product in patients with primary immunodeficiency and idiopathic thrombocytopenic purpura

In the production process of a new 5% liquid intravenous immunoglobulin (IVIG-L) product (Nanogam(®) ), a combined pepsin/pH 4·4 treatment/15-nm filtration (pH 4·4/15NF) step and a solvent-detergent (SD) treatment step were incorporated to improve the virus inactivating/reducing capacity of the manufacturing process. Two prospective uncontrolled multicentre studies were performed to evaluate the safety and efficacy of this product. Efficacy, including pharmacokinetics, of IVIG-L was studied for 6 months in 18 primary immunodeficiency (PID) patients, succeeded by a long-term follow-up study (mean 2·2 years, n=17). Second, in 24 patients with idiopathic thrombocytopenic purpura (ITP), IVIG-L was studied for efficacy for 14 days. In both studies, adverse events and vital signs were recorded to study safety. In PID patients treated with IVIG-L, 0·60 and 0·38 severe infections per patient per year were reported during, respectively, the short-term and long-term follow-up. Pharmacokinetic studies resulted in an IgG half-life of 30·9 ± 11·3 days and a mean IgG trough level of 6·8 ± 1·2 g/l. In the ITP study, all patients showed an increase in platelet counts after infusion with IVIG-L, and 20/24 patients responded with a platelet count >50 × 10(9) /l (83·3%) within 1 week. IVIG-L infusions did not cause clinical relevant changes in laboratory parameters or vital signs. In clinical studies, IVIG-L (Nanogam®) demonstrated to be efficacious, well tolerated and safe.

Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy

BackgroundDifferent preparations of intravenous immunoglobulin (IVIg) are considered to have comparable clinical efficacy but this has never been formally investigated. Some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report that...