Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of personalized medicine. In this review article, we provide an overview of the taxonomy, pharmacology, and therapeutic applications of MAbs in glomerular diseases. We searched the literature through PubMed using the following search terms: monoclonal antibodies, glomerular diseases, pharmacokinetics, pharmacodynamics, immunoglobulin, murine, chimeric,humanized, and fully human, and limited our search to years 2018-2023. We selected peer-reviewed journal articles with an evidence-based approach, prioritizing randomized control trials in specific glomerular diseases, if available. Advances in the MAb field have resulted in a significant paradigm shift in targeted treatment of immune-mediated glomerular diseases, and multiple randomized control trials are currently being conducted. Increased recognition is critical to expand their use in experimental research and personalized medicine.

Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N = 1,091) compared to propensity score (PS) matched control (N = 1,091). The primary composite outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary composite outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p = 0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (<65 years or ≥65), and immunocompromised status (patients with HIV/AIDS or solid organ transplants or malignancy including lymphoproliferative disorder). The number needed to treat (1/0.026-0.022) with BEB MAb was 250 to avoid one hospitalization and/or death over 30 days. The BEB MAb use lacked efficacy in patients with SARS-CoV-2 Omicron subvariants (mainly BA.2, BA.2.12.1, and BA.5) in the Banner Healthcare System in the Southwestern United States.

The Impact of Nirmatrelvir-Ritonavir in Reducing Hospitalizations Among High-Risk Patients With SARS-CoV-2 During the Omicron Predominant Era.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality in high-risk populations. Several therapeutics have been developed to reduce the risk of complications related to COVID-19, hospitalizations, and death. In several studies, nirmatrelvir-ritonavir (NR) was reported to reduce the risk of hospitalizations and death. We aimed to evaluate the efficacy of NR in preventing hospitalizations and death during the Omicron predominant period. METHODS: We retrospectively evaluated patients from June 1, 2022, through September 24, 2022. There were a total of 25,939 documented COVID-19 cases. Using propensity matching, we matched 5754 patients treated with NR with untreated patients. RESULTS: Postmatching, the median age of the NR-treated group was 58 years (interquartile range, 43-70 years) and 42% were vaccinated. Postmatching composite outcome of the 30-day hospitalization and mortality in the NR-treated group were 0.9% (95% confidence interval [CI]: 0.7%-1.2%) versus 2.1% (95% CI: 1.8%-2.5%) in the matched control group, with a difference of -1.2 (-1.7, -0.8), P value <.01. The difference rates (NR vs. control) in 30-day all-cause hospitalizations and mortality were -1.2% (95% CI: -1.6% to -0.7%, P value <.01) and -0.1% (95% CI: -0.2% to 0.0%, P value = 0.29), respectively. We found similar finding across different age groups (≥65 vs. <65) and the vaccinated group. CONCLUSION: We report a significant benefit with the use of NR in reducing hospitalizations among various high-risk COVID-19 groups during the Omicron BA.5 predominant period.

Effectiveness of Casirivimab-Imdevimab Monoclonal Antibody Treatment Among High-Risk Patients With Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617.2 (Delta Variant) Infection.

Background: Real-world data on the effectiveness of neutralizing casirivimab-imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. Methods: This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Of 29 635 patients who tested positive for coronavirus disease 2019 (COVID-19) between 1 August 2021 and 30 October 2021, in the Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a PS-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or Delta variant infection. Results: Compared to the PS-matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%; difference in percentages, -13.4 [95% confidence interval {CI}, -14.7 to -12.0]; P < .001), ICU admission (0.3% vs 2.8%; difference, -2.4 [95% CI, -3.0 to -1.9]; P < .001), and mortality (0.2% vs 2.0%; difference, -1.8 [95% CI, -2.3 to -1.3]; P < .001) within 30 days. The Cas-Imd mAb treatment was associated with lower rate of hospitalization (hazard ratio [HR], 0.22 [95% CI, .19-.26]; P < .001) and mortality (HR, 0.11 [95% CI, .06-.21]; P < .001). Conclusions: Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with the SARS-CoV-2 Delta variant.

Glucose-Lowering Medications and Cardiovascular Outcomes.

PURPOSE OF THE REVIEW: The purpose of this review is to examine recent evidence supporting CV safety profile and improvement of CV outcomes of some of the newer classes of diabetic medications. RECENT FINDINGS: Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease (CVD). Thus, CVD management is critical in diabetic patients. Since 2008, the US Food and Drug Administration (FDA) has mandated that all newer diabetic medications should establish cardiovascular safety before it is approved for use. Diabetic medications that also lower CV risk would be a significant advancement as shown in recent studies. There are 3 new class of diabetic medications: Dipeptidyl peptidase-4 inhibitors (DPP-4), glucagon-like peptide receptor agonists (GLP-1 RA), and sodium-glucose cotransporter type 2 (SGLT 2) inhibitors which have established both CV safety and improvement in CV outcomes with some drugs. In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, multiple atherosclerotic cardiovascular disease risk factors, or diabetic kidney disease, a sodium-glucose cotransporter 2 inhibitor, or a glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events.

Outcomes of Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention Analysis of National Inpatient Sample.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence of 15% of patients over 80 years. Coronary artery disease co-exists in 20-30% of patients with atrial fibrillation. The need for triple anticoagulation therapy makes the management of these patients challenging following PCI. METHODS: Nationwide inpatient sample which is a set of longitudinal hospital inpatient databases was used to evaluate the outcome of patients with AF who underwent PCI. All patients undergoing PCI between 2002 and 2011 were included in the study. Specific ICD-9-CM codes were used to identify the study patients and their outcomes. RESULTS: There were 3,226,405 PCIs during the time period of the study of which 472,609 (14.6%) patients had AF. AF patients were older and predominantly male (60%). The number of PCIs had a declining trend from 2002 to 2011. Age adjusted inpatient mortality was significantly higher in PCI AF group compared to the PCI non-AF group (100.82 ±â€¯9.03 vs 54.07 ±â€¯8.96 per 100,000; P < 0.01). Post PCI predictors of mortality were AF (OR 1.56, CI 1.53-1.59), CKD (OR 1.41, CI 1.37-1.46), PAD (OR 1.20, CI 1.15-1.24), acute myocardial infarction (OR 2.42 CI 2.37-2.46 and cardiogenic shock (OR 13.92 CI 13.60-14.24) P < 0.001. CONCLUSION: AF is common in patients undergoing PCI and those AF patients have a higher age-adjusted all cause inpatient mortality. There is a decline in total number of PCIs over time in US. Atrial fibrillation, chronic kidney disease, peripheral artery disease, MI and cardiogenic shock were associated with increased mortality following PCI.

Drug-coated balloon in peripheral artery disease.

Peripheral artery disease (PAD) is highly prevalent but is often underdiagnosed and undertreated. Lower extremity PAD can often be life style limiting. Revascularization in carefully selected lower extremity PAD patients improves symptoms and functional status. Surgical revascularization used to be the only available strategy, but in the recent years, endovascular strategies have gained popularity due to faster recovery times with low morbidity and mortality rates. Endovascular procedures have increased significantly in the United States in the past few years. That being said, higher restenosis rates and low long-term patency rates have been the limiting factors for this strategy. Drug eluting stents have been introduced to help with lowering restenosis, however lower extremity PAD involves long segment where the outcomes of stents are suboptimal. Also, the disease often crosses joint line that makes it less ideal for the stents. Drug-coated balloons (DCB) have been introduced to improve patency rates following endovascular intervention for lower extremity PAD. They have gained popularity among endovascular specialists due to its ease of use and the concept of "leave nothing behind". This is a review of scientific evidence supporting DCB use in PAD.

Epidemiology of Glomerular Disease in Southern Arizona: Review of 10-Year Renal Biopsy Data.

Glomerulonephritis stands third in terms of the etiologies for end-stage kidney disease in the USA. The aim of this study was to look at the patterns of biopsy-proven glomerulonephritis based on data from a single center.Kidney biopsy specimens of all patients above the age of 18 years, over a 10-year period, who had diagnosis of nondiabetic glomerular disease, were selected for the study.The most common histopathological diagnosis was focal and segmental glomerulosclerosis (FSGS) (22.25%, 158/710) followed by membranous nephropathy (20.28%, 144/710) and immunoglobulin (Ig)A nephropathy (19.71%, 140/710). There was male preponderance in all histological variants except IgA nephropathy, lupus nephritis, and pauci-immune glomerulonephritis. The race distribution was uneven, and all histological variants, except minimal change disease and lupus nephritis, were more commonly seen in whites. In a separate analysis of the histological pattern in Hispanics, lupus nephritis was the most common pathology (28.70%, 62/216) followed by FSGS (18.05%, 39/216). In American Indian population, the most common pathology was IgA nephropathy (33.33%, 8/24) followed by FSGS (16.67%, 4/24).This study highlights the histopathological patterns of glomerular disease in southern Arizona. The data suggest regional and ethnic variations in glomerular disease that may point towards genetic or environmental influence in the pathogenesis of glomerular diseases.

Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

Outcome of Patients with Infective Endocarditis who were Treated with Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.

Infective endocarditis is a potentially life threatening condition. It is associated with high mortality and morbidity resulting mostly due to cardiorespiratory failure. Extracorporeal membrane oxygenation is a modality of treatment used to support hypoxic respiratory failure especially in patients who are already on mechanical ventilation. Continuous renal replacement therapy is added mainly for maintaining fluid and electrolyte balance. Here we report a case series of patients diagnosed with infective endocarditis who were treated with combined extracorporeal membrane oxygenation and continuous renal replacement therapy. Three patients in the age group 20-60 years were admitted with clinical features suggestive of infective endocarditis. During the course of hospital stay they developed cardiorespiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation support for refractory hypoxia. It was complicated by heart failure, renal failure and fluid overload which required initiation of continuous renal replacement therapy. All the three patients succumbed in spite of the aggressive treatment. In addition to the role played by each complication, delayed start of continuous renal replacement therapy might have also contributed to the high mortality. Early initiation of continuous renal replacement therapy for management of fluid overload needs to be considered in the management of these critically ill patients.