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.

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 Endoscopic band ligation compared to thermal therapy for gastric antral vascular ectasia: A systematic review and meta-analysis

2020 ◽  
pp. 205064062097524
Author(s):  
Jean M Chalhoub ◽  
Jalaluddin Umar ◽  
Kevin Groudan ◽  
Nour Hamadeh ◽  
David J Desilets ◽  
...  
Keyword(s):  
Adverse Events ◽  
Confidence Interval ◽  
Thermal Therapy ◽  
Gastric Antral Vascular Ectasia ◽  
Band Ligation ◽  
Vascular Ectasia ◽  
Transfusion Requirements ◽  
Endoscopic Band Ligation ◽  
The Mean

Background Gastric antral vascular ectasia is an infrequent cause of gastrointestinal-related blood loss manifesting as iron-deficiency anemia or overt gastrointestinal bleeding, and is associated with increased healthcare burdens. Endoscopic therapy of gastric antral vascular ectasia most commonly involves endoscopic thermal therapy. Endoscopic band ligation has been studied as an alternative therapy with promising results in gastric antral vascular ectasia. Aims The primary aim was to compare the efficacy of endoscopic band ligation and endoscopic thermal therapy by argon plasma coagulation for the management of bleeding gastric antral vascular ectasia in terms of the mean post-procedural transfusion requirements and the mean hemoglobin level change. Secondary outcomes included a comparison of the number of sessions needed for cessation of bleeding, the change in transfusion requirements, and the adverse events rate. Methods PubMed, Medline, SCOPUS, Google Scholar, and the Cochrane Controlled Trials Register were reviewed. Randomized controlled clinical trials and retrospective studies comparing endoscopic band ligation and endoscopic thermal therapy in bleeding gastric antral vascular ectasia, with a follow-up period of at least 6 months, were included. Statistical analysis was done using Review Manager. Results Our search yielded 516 papers. After removing duplicates and studies not fitting the criteria of selection, five studies including 207 patients were selected for analysis. Over a follow-up period of at least 6 months, patients treated with endoscopic band ligation had significantly lower post-procedural transfusion requirements (MD −2.10; 95% confidence interval (−2.42 − −1.77)) and a significantly higher change in the mean hemoglobin with endoscopic band ligation vs endoscopic thermal therapy (MD 0.92; 95% confidence interval (0.39 − 1.45)). Endoscopic band ligation led to a fewer number of required sessions (MD −1.15; 95% confidence interval (−2.30 − −0.01)) and a more pronounced change in transfusion requirements (MD −3.26; 95% confidence interval (−4.84 − −1.68)). There was no difference in adverse events. Conclusion Results should be interpreted cautiously due to the limited literature concerning the management of gastric antral vascular ectasia. Compared to endoscopic thermal therapy, endoscopic band ligation for the management of bleeding gastric antral vascular ectasia led to significantly lower transfusion requirements, showed a trend toward more remarkable post-procedural hemoglobin elevation, and a fewer number of procedures. Endoscopic band ligation may improve outcomes and lead to decreased healthcare burden and costs.

scholarly journals Influence of Flunixin on the Disposition Kinetic of Cefepime in Goats

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Mohamed El-Hewaity
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Intramuscular Injection ◽  
Test Organism ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Serum ◽  
Maximum Serum Concentration ◽  
The Mean

The pharmacokinetic profile of cefepime (10 mg/kg b.w.) was studied following intravenous and intramuscular administration of cefepime alone and coadministered with flunixin (2.2 mg/kg b.w.) in goats. Cefepime concentrations in serum were determined by microbiological assay technique usingEscherichia coli(MTCC 443) as test organism. Following intravenous injection of cefepime alone and in combination with flunixin, there are no significant changes in the pharmacokinetic parameters. Following intramuscular injection of cefepime alone and in combination with flunixin, the maximum serum concentration was significantly increased in flunixin coadministered group compared with cefepime alone. However, no significant changes were reported in other pharmacokinetic parameters. The result ofin vitroprotein binding study indicated that 15.62% of cefepime was bound to goat’s serum protein. The mean bioavailability was 92.66% and 95.27% in cefepime alone and coadministered with flunixin, respectively. The results generated from the present study suggest that cefepime may be coadministered with flunixin without change in dose regimen. Cefepime may be given intramuscularly at 12 h intervals to combat susceptible bacterial infections.

scholarly journals Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Cong Zhao ◽  
Meng Pu ◽  
Dawei Chen ◽  
Jin Shi ◽  
Zhuyi Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Confidence Interval ◽  
Myasthenia Gravis ◽  
Meta Analysis ◽  
Immunosuppressive Agents ◽  
Cochrane Library ◽  
Score Change ◽  
Randomized Controlled ◽  
The Mean

Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10–30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG.Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants.Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49–77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88–2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10–1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66–93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy.Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.

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 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)

Fluid Extravasation during Hip Arthroscopy

2011 ◽  
Vol 21 (6) ◽  
pp. 740-743 ◽  
Author(s):  
Giles H. Stafford ◽  
Ajay Malviya ◽  
Richard N. Villar
Keyword(s):  
Adverse Events ◽  
Confidence Interval ◽  
Hip Arthroscopy ◽  
Soft Tissues ◽  
Arthroscopic Surgery ◽  
Operating Time ◽  
Irrigation Fluid ◽  
Fluid Extravasation ◽  
Infusion Pressure ◽  
The Mean

The amount of fluid that may be lost into the soft tissues during hip arthroscopic surgery is unknown. We measured the volumes of irrigation fluid infused, operating time, fluid pressures and volumes of fluid recovered in 36 therapeutic hip arthroscopies. We excluded those where fluid was lost to the floor, leaving 28 patients. The majority were undergoing surgery for the treatment of femoroacetabular impingement. In 5 patients an intra-articular contrast medium was instilled, in order to establish the likely location of any extravasated fluid. The mean operating time was 68 minutes (31 to 120), and the mean infusion pressure was 46 mm Hg (30 to 70). The mean volume of infused fluid was 9677 ml (95% confidence interval (CI) 7715 to 11638) and the mean volume of fluid recovered was 8544 ml (95% CI 6715 to 10373). The mean fluid extravasation loss into the peri-articular tissues was 1132 ml (95% CI 808 ml to 1456 ml). There was a significant correlation between the volume of extravasated fluid and both the length of operation and the volume of infused fluid used. We had no adverse events in our series. During arthroscopic hip surgery more than a litre of irrigation fluid may be extravasated into the soft tissues. In order to reduce problems related to this we attempt to keep operating times low, and maintain intra-operative fluid pressures as low as possible.

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