scholarly journals Efficacy, safety, and tolerability of IVIG-SN in patients with primary immunodeficiency

2015 ◽  
Vol 2 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Mark R. Stein ◽  
Richard L. Wasserman ◽  
James Moy ◽  
William Lumry ◽  
Eyal Grunebaum ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Bacterial Infections ◽  
Antibiotic Use ◽  
Efficacy And Safety ◽  
Pathogen Elimination ◽  
Ivig Preparation ◽  
Adults And Children ◽  
Serious Bacterial Infections ◽  
Trough Levels ◽  
Multiple Pathogen

Background: IVIG-SN is a modern intravenous immunoglobulin with multiple pathogen elimination steps. This clinical trial in patients with primary immunodeficiency (PID) was designed to evaluate the safety, efficacy, and tolerability of this product in adults and children. Methods: Forty-four patients with PID were treated with IVIG-SN for 12 months. IgG trough levels and pharmacokinetics of IVIG-SN were evaluated as well as efficacy and safety according to standard FDA guidelines. Results: Overall, a total of 572 IVIG-SN infusions were administered according to either a 21- or a 28-day schedule. IgG trough levels during the treatment period ranged from 823.00 to 902.77 mg/dL, respectively, and half-life in serum of the administered IgG was 43.45 ± 30.25 days. There were no deaths and no adverse events leading to withdrawal from the study. Of all infusions administered, only 137 (24%) were temporally associated with an adverse event (AE). The upper bound for the 95% CI for the frequency of infusions temporally associated with an AE was 29.2%. Drug-related AEs were predominantly mild, and there were no acute serious bacterial infections during the study. Efficacy was also demonstrated by low rates of missed work, school, or daycare days (mean 2.6 days); unscheduled visits to physicians (mean 1.7); and therapeutic antibiotic use (mean 15 days). Conclusion: IVIG-SN is effective in preventing infections and is safe and well tolerated. Statement of novelty: This efficacy and toxicity trial was conducted using a new IVIG preparation.

scholarly journals Efficacy, safety, and tolerability of Kedrion 10% IVIG in primary immunodeficiency

2016 ◽  
Vol 3 (3) ◽  
pp. 99-109 ◽  
Author(s):  
Mark Stein ◽  
Agnes Nemet ◽  
Santhosh Kumar ◽  
William Lumry ◽  
Hartwig Gajek ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Confidence Limit ◽  
Bacterial Infections ◽  
Phase Iii ◽  
Open Label ◽  
Safety Endpoint ◽  
Ivig Preparation ◽  
Phase Iii Study ◽  
Serious Bacterial Infections ◽  
Primary Safety Endpoint

Background: Primary immunodeficiency involving defective antibody formation requires antibody replacement therapy with immunoglobulin products to prevent and reduce infections. Immunoglobulin for intravenous use (IVIG) is a processed blood product with limited availability, and the various marketed IVIG products may have different tolerability among patients. New IVIG products are therefore necessary to offer options to patients and to reduce the risk of a product shortage. Methods: Forty-five adult and pediatric patients with primary immunodeficiency, documented agammaglobulinemia or hypogammaglobulinemia, and antibody deficiency were enrolled in a prospective, multi-centre, open-label, single-arm historically controlled Phase III study to evaluate the safety, efficacy, and pharmacokinetics of a new 10% IVIG produced by Kedrion. Results: Forty-four patients completed the study while one withdrew consent. Over the 12-month study period, only 2 episodes of acute serious bacterial infections (both bacterial pneumonias) were recorded, for a mean annual event rate of 0.04 per subject, with an upper one-sided 99% confidence limit of 0.11. Values for all secondary efficacy endpoints were comparable with those in similar studies. The primary safety endpoint was met as the rate of infusions temporally associated (i.e., within 72 hours) with ≥1 adverse event was 16% (upper 95% confidence limit 20.4%). Pharmacokinetics were assessed in 31 patients and found to be comparable with those published for other IVIG products. Conclusion: Kedrion IVIG 10% is safe, efficacious, and well tolerated by patients with primary immunodeficiency. Statement of novelty: This report describes the safety, efficacy, and pharmacokinetics of a new IVIG preparation.

scholarly journals Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases

Immunotherapy ◽  
2021 ◽  
Author(s):  
Richard L Wasserman ◽  
Sudhir Gupta ◽  
Mark Stein ◽  
Christopher J Rabbat ◽  
Werner Engl ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Bacterial Infections ◽  
Similar Efficacy ◽  
Treatment Modalities ◽  
Primary Immunodeficiency Diseases ◽  
Infection Rates ◽  
Clinical Trial Registration ◽  
Immunodeficiency Diseases ◽  
Serious Bacterial Infections ◽  
Post Hoc

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871 , NCT00814320 , NCT01175213 (ClinicalTrials.gov)

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena E. Perez ◽  
Jacques Hébert ◽  
Anne K. Ellis ◽  
Oral Alpan ◽  
William R. Lumry ◽  
...  
Keyword(s):  
Adverse Events ◽  
Confidence Interval ◽  
Intravenous Immunoglobulin ◽  
Primary Immunodeficiency ◽  
Bacterial Infections ◽  
Pharmacokinetic Parameters ◽  
Oral Antibiotic ◽  
Serious Bacterial Infections ◽  
The Mean ◽  
Confidence Interval Limit

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.

Procalcitonin Testingreduce Unnecessary Antibiotic Use in Bacterial Infection

2019 ◽  
Vol 2 (1) ◽  
pp. 1-3
Author(s):  
Attabak Toofani Milani ◽  
Mahshid Mohammadian ◽  
Sadegh Rostaminasab ◽  
Roghayeh Paribananaem ◽  
Zohre Ahmadi ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Bacterial Infection ◽  
Diagnostic Test ◽  
Bacterial Infections ◽  
Intervention Studies ◽  
Antibiotic Use ◽  
Clinical Suspicion ◽  
Diagnostic Biomarker ◽  
Clinical Routine ◽  
Initial Rise

Conventional diagnostic test have limitations to deferential diagnosis in clinical suspicion ofbacterial infection cases, that in some cases lead to inappropriate antibiotic therapy and increases antibiotic resistance. A new diagnostic insight is procalcitonin (PCT) test to improve diagnosis of bacterial infections and to guide antibiotic therapy. Serum PCT levels are of useful test as a biomarker in patients with bacterial infections for several reasons. Initial rise of PCT levels due to bacterial infection, subsequent sequential PCT levels can be used to assess the effectiveness and duration of antibiotic therapy. Based on clinical researches results, in bacterial infections, promising good results obtained when use of PCT used as differential diagnostic test. But further intervention studies are needed before use of PCT in clinical routine tests. The goal of this review is to study the PCT reliability as infections diagnostic biomarker.

ОЦЕНКА ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ 10% ВНУТРИВЕННОГО ИММУНОГЛОБУЛИНА ПРИВИДЖЕН В РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКЕ

2019 ◽  
Author(s):  
L.G. Khludova ◽  
I.A. Manto ◽  
E.A. Latysheva ◽  
T.V. Latysheva ◽  
M.R. Khaitov
Keyword(s):  
Replacement Therapy ◽  
Primary Immunodeficiency ◽  
Adverse Reactions ◽  
Efficacy And Safety ◽  
High Efficacy ◽  
Antibody Synthesis ◽  
Human Immunoglobulins ◽  
Severe Adverse Reactions ◽  
Common Variable ◽  
Real Clinical Practice

Актуальность. Заместительная терапия иммуноглобулинами человека является ведущим патогенетическим методом лечения первичных иммунодефицитов с нарушением синтеза антител. В настоящее время в России доступно несколько препаратов иммуноглобулинов человека нормальных для внутривенного введения. Цель. Оценить эффективность и безопасность препарата Привиджен (10 раствор иммуноглобулина для внутривенного введения) в реальной клинической практике в течение 12 клинических месяцев. Материалы и методы. 20 взрослых с диагнозом общая вариабельная иммунная недостаточности и Х-сцепленная агаммаглобулинемия получали внутривенный иммуноглобулин Привиджен к интервалом 243 дня в течение 12 мес. Первичными критериями оценки была частота инфекционных осложнений и нежелательных явлений. Результаты. У большинства пациентов в ходе исследования достигнут удовлетворительный претранс-фузионный уровень IgG. Тяжелых нежелательных явлений, связанных с введением препарата, не зарегистрировано. Заключение. В ходе исследования препарат продемонстрировал высокую эффективность и безопасность у пациентов, нуждающихся в ежемесячной заместительной терапииRelevance. Replacement therapy with human immunoglobulins is the leading pathogenetic method of treatment of primary immunodeficiency with impaired antibody synthesis. Currently, several preparations of human immunoglobulins for intravenous administration are available in Russia. Purposes. Evaluation of the efficacy and safety of Privigen immunoglobulin intravenous 10 liquid in real clinical practice within 12 clinical months. Methods. Twenty adults diagnosed with common variable immunodeficiency or X-linked agammaglobulinemia received intravenous Privigen infusions (0.2-0.4 mg/kg) at 243 intervals over a 12-month period. The primary endpoint was the annual rate of infections and adverse events. Results. Sufficient level of IgG was achieved in most patients during the study. Severe adverse reactions during the treatment were not registered. Conclusions. High efficacy and safety of monthly replacement therapy in patients with primary immunodeficiency with impaired antibody synthesis has been demonstrated.

#53: High Burden of Serious Bacterial Infections in African Children Treated for Cancer

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S6-S6
Author(s):  
G Naidu ◽  
A Izu ◽  
R Wainwright ◽  
S Poyiadjis ◽  
D MacKinnon ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Case Fatality ◽  
Morbidity And Mortality ◽  
Coagulase Negative Staphylococci ◽  
Children With Cancer ◽  
Indwelling Catheter ◽  
High Burden ◽  
African Children ◽  
Serious Bacterial Infections ◽  
Living With Hiv

Abstract Background Infectious complications in children treated for cancer contribute to their morbidity and mortality. There is a paucity of studies on the incidence, microbiological etiology, risk factors, and outcome of serious bacterial infections in African children treated for cancer. Aim The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in South African children with cancer. Methods This prospective, single-center, longitudinal-cohort study enrolled children one-19 years old hospitalized for cancer treatment at the Paediatric Oncology Unit, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Children were investigated for infection as part of the standard of care. Results In total, 169 children were enrolled, 82 with hematological malignancy (HM), 87 with a solid tumor (ST), median age was 68.5 months and 10.7% were living with HIV. The incidence (per 100 child-years) of septic episodes (SE) and microbiologically confirmed SE (MSCE) was 101 (138 vs. 70, P < 0.001) and 70.9 (99.1 vs. 47.3; P < 0.001), respectively; higher in children with HM than ST. The incidence of MCSE in children with high-risk HM (137.7) was 4.32-fold greater compared with those with medium-risk HM (30.3; P < 0.001). Children with metastatic ST had a higher incidence (84.4) of MSCE than those with localized ST (33.6; aOR: 2.52; P < 0.001). The presence of an indwelling catheter was 3-fold (P < 0.001) more likely to be associated with MCSE compared with those without. There was no association for age group, nutritional status or HIV-status, and incidence of MCSE. The incidence of gram-positive (GPB) and gram-negative (GNB) SEs was 48.5 and 37.6, respectively, and higher in children with an HM. The most commonly identified GPB were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium; while the most common GNB were Escherichia coli, Acinetobacter baumannii, and Pseudomonas species. The median CRP was higher in children with MSCE compared with those with culture-negative SE (CNSE) (116.5 vs. 92; P < 0.001) in both HM (132.5 vs. 117; P < 0.001) and ST (87.5 vs. 46; P < 0.001). The procalcitonin was higher in those with MSCE compared with those with CNSE (2.30 vs. 1.40; P < 0.001) in both HM (2.95 vs. 1.60; P = 0.002) and ST (2.10 vs. 1.20; P < 0.001). The case fatality risk was 40.4%; 80% was attributed to sepsis. Of these, 35 (72.92%) had HM and 34 of the 35 (97.14%) had HR-HM. Children with HM had an overall sepsis CFR of 42.68%. Four (30.77%) of the 13 sepsis-related deaths in STs had metastatic disease and 8 (16.67%) of the total number of sepsis-related deaths were in children living with HIV. There was no association between malnutrition or HIV-positivity and death. The odds of dying from sepsis were higher in children with profound (aOR 3.96; P = 0.004) and prolonged (aOR 3.71; P = 0.011) neutropenia. Pneumonia (58.85% vs. 29.23%; aOR 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR 4.3; P = 0.005) were independently associated with a higher CFR. Conclusion The current study emphasizes the high burden of sepsis in African children treated for cancer, and especially HM, and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.

scholarly journals How reliable is procalcitonin as an inflammatory marker?1)

2012 ◽  
Vol 35 (6) ◽  
pp. ---
Author(s):  
Katharina Biller ◽  
Peter Fae ◽  
Reinhard Germann ◽  
Autar K. Walli ◽  
Peter Fraunberger
Keyword(s):  
Intensive Care ◽  
Diagnostic Tool ◽  
Plasma Levels ◽  
Bacterial Infections ◽  
Respiratory Tract Infections ◽  
Inflammatory Marker ◽  
Antibiotic Use ◽  
Intensive Care Patients ◽  
Tract Infections

Abstract The role of procalcitonin (PCT) plasma levels as a diagnostic tool for intensive care patients has been intensively investigated during the past years. In particular for recognition of bacterial infections, PCT levels have been shown to be superior to other clinical and biochemical markers. Furthermore, some very recent studies show that in patients with lower respiratory tract infections PCT guided antibiotic therapy reduces antibiotic use and thereby may also reduce duration of stay of patients in hospital and thus cut hospitalisation costs. However, various studies indicate that the value of PCT as a prognostic marker is limited because of false positive or negative values. Despite these limitations PCT plasma levels are currently measured in intensive care units. The present study summarises the possible clinical uses of this laboratory marker as a diagnostic tool for the assessment of critically ill patients.

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