Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden.

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome.

BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.

Apolipoprotein A1 and Ceruloplasmin, the key crosstalk players between the liver and adipose tissue during early postpartum of buffaloes: An in-Silico transcriptome based network analysis.

Physiological transition from pregnancy to lactation during early postpartum creates a high-energy demand in females towards milk production for the survival of new offspring. Ruminant milk contains high amount of lactose, a disaccharide of the glucose and galactose. The milk yield of the animals is also dependent on the lactose amount. In ruminants, glucose is majorly supplied by the liver, which obtains energy from the adipose tissue during energy demands. Therefore, there should be an intricate crosstalk between these two tissues for efficient maintenance of energy for normal physiological needs and milk production. In the present study, we analyzed the transcriptome data previously obtained from the buffalo liver and adipose tissue on the 15th day and 30th day of lactation by using several bioinformatics tools such as PANTHER, Secretome-P, STRING and CPDB. Our analysis identified a total of 24 signaling molecules as interactive players between the liver and adipose tissue during early postpartum of buffaloes. Particularly, the liver appears to interact with the adipose tissue and itself majorly through an endocrine/autocrine molecule, APOA1. Similarly, the adipose tissue appears to interact with the liver and itself majorly through an endocrine/autocrine molecule, CP (ceruloplasmin). The APOA1 and CP may counteract with each other on lipolysis in buffalo adipose tissue because of their common signaling molecules being shared. In addition, the interaction between the adipose derived ceruloplasmin and the liver derived lactoferrin seems to be important during early postpartum of buffaloes. The importance of this interaction needs to be studied in further studies.

COVID-19-Associated Collapsing Focal Segmental Glomerulosclerosis: A Report of 2 Cases.

Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse causes. The presence of the apolipoprotein L1 (APOL1) high-risk genotype is a major risk factor for collapsing glomerulopathy in African Americans. Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations. However, kidney involvement is being frequently noted and is associated with higher mortality. Currently, kidney pathology data for COVID-19 are scant and mostly come from postmortem findings. We report 2 African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 infection. Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells. Both patients had the APOL1 high-risk genotype. We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 infection, especially in people of African descent with APOL1 risk alleles.

Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience.

BACKGROUND: Contrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase in mortality and morbidity. Data regarding CIN in renal allografts are limited, however. We retrospectively studied CIN in renal allografts at our institution: its incidence, risk factors, and effect on long-term outcomes including allograft loss and death. METHODS: One hundred thirty-five renal transplant recipients undergoing 161 contrast-enhanced computed tomography (CT) scans or coronary angiograms (Cath) between years 2000 and 2014 were identified. Contrast agents were iso- or low osmolar. CIN was defined as a rise in serum creatinine (SCr) by >0.3 mg/dl or 25% from baseline within 4 days of contrast exposure. After excluding 85 contrast exposures where patients had no SCr within 4 days of contrast administration, 76 exposures (CT: n = 45; Cath: n = 31) in 50 eligible patients were analyzed. Risk factors assessed included demographics, comorbid conditions, type/volume of contrast agent used, IV fluids, N-acetylcysteine administration, and calcineurin inhibitor use. Bivariate and multivariable analyses were used to assess the risk of CIN. RESULTS: Incidence of CIN was 13% following both, CT (6 out of 45) and Cath (4 out of 31). Significant bivariate predictors of CIN were IV fluid administration (p = 0.05), lower hemoglobin (p = 0.03), and lower albumin (p = 0.02). In a multivariable model, CIN was predicted by N-acetylcysteine (p = 0.03) and lower hemoglobin (p = 0.01). Calcineurin inhibitor use was not associated with CIN. At last follow-up, CIN did not affect allograft or patient survival. CONCLUSION: CIN is common in kidney transplant recipients, and there is room for quality improvement with regards to careful renal function monitoring post-contrast exposure. In our study, N-acetylcysteine exposure and lower hemoglobin were associated with CIN. Calcineurin inhibitor use was not associated with CIN. Our sample size is small, however, and larger prospective studies of CIN in renal allografts are needed.