Analysis Group (United States)

Venetoclax plus azacitidine or decitabine is approved in the US for treatment of newly diagnosed patients with acute myeloid leukemia (AML) aged ≥ 75years or who have comorbidities precluding use of intensive chemotherapy. As novel targeted regimens expand treatment options for AML, this study evaluated the budget impact of adopting venetoclax combinations for this population from a US third-party payer perspective to inform affordability and access at the health plan level. The model estimated the 3-year budget impact of adopting venetoclax combinations in a hypothetical US health plan with 1 million members (60% commercial, 40% Medicare). Eligible patients were estimated using public data. Market share projections assumed venetoclax + azacitidine or decitabine captured a 53% and 15% share, respectively, from existing treatments (azacitidine, low-dose cytarabine [LDAC], decitabine, ivosidenib, gemtuzumab ozogamicin, glasdegib + LDAC, and ivosidenib + azacitidine). The model considered costs associated with drug acquisition/administration, adverse events, hospitalization, disease monitoring, blood transfusions, and subsequent AML management (2024 USD). Clinical inputs for venetoclax combinations were informed by final VIALE-A and M14-358 data, respectively. Incremental budget impact was calculated as per-member-per-month (PMPM), with one-way sensitivity analyses performed. In a 1-million-member health plan, 48 patients were eligible for venetoclax combinations. Annual costs of venetoclax + azacitidine ($258,498) or decitabine ($259,921) were lower than those of the highest-cost comparators, ivosidenib + azacitidine ($477,520) and ivosidenib ($404,869). Drug acquisition costs of adopting venetoclax combinations were offset by lower subsequent AML management costs, resulting in savings of $0.0476 PMPM in years 1-3. Results remained robust in sensitivity analyses. In a 100% Medicare scenario, 117 patients were eligible for venetoclax combinations, with savings of $0.1137 PMPM over years 1-3. Inclusion of venetoclax combinations for newly diagnosed patients with AML aged ≥ 75years or with comorbidities precluding intensive chemotherapy reduced the budget impact, providing potential financial benefits for US payers.

PGA less than 0.5, prednisone less than 5mg/day, and stable immunosuppressants).LLDAS was defined as SLEDAI-2K less than 4, no major organ activity, no new disease activity, PGA less than 1, and prednisone less than 7.5mg/day.Organ damage was measured with the SLICC/ACR Damage Index (SDI).Patient-reported outcomes (PROs) included HAQ and Lupus Impact Tracker (LIT).Associations between HAQ, SDI and remission status were analyzed.Results We studied 339 patients (89.1% female, mean age 53.2 14.6 years, median disease duration 127 months), 22.9% had lupus nephritis and 37.6% were receiving corticosteroids.Antimalarial use was common (80.6%).At evaluation, 57.9% fulfilled DORIS remission and 84.9% were in LLDAS.Nonetheless, 42.2% had SDI equal to 1 and 23.3% SDI equal to 2. Interestingly, 52.9% of patients not in remission or LLDAS had no damage (SDI=0).Among those in remission, 81% had HAQ scores between 0-1, compared to 60.7% of patients not achieving remission.Spearman's correlation showed a significant association between HAQ and SDI (r=0.42;p<0.001).Correlations between remission status and HAQ (r=-0.31)and remission status and SDI (r=-0.28)were weaker but significant.Conclusions A high proportion of patients achieved LLDAS (84.9%) and DORIS remission (57.9%).Still, 42.2% in remission had organ damage (SDI equal to 1), showing poor correlation between activity and damage.Thus, both indices should be assessed separately.HAQ correlated better with SDI, suggesting functional status reflects cumulative damage more reliably than activity alone.

Objectives LN increases the risk of end-stage kidney disease and mortality.Belimumab selectively inhibits B-lymphocyte stimulator, and has been shown to prevent organ damage progression in SLE and preserve kidney function in LN.We evaluated whether belimumab is associated with a lower risk of progression to LN among patients with SLE versus standard of care (SOC) in real-world practice.Methods A retrospective, longitudinal cohort study (GSK Study 217533) using claims linked with electronic health record data (Optum Market Clarity database).Index: date of initiation of belimumab or SOC (immunosuppressant [IS, except as LN initial therapy], intravenous glucocorticoids [GCs], or oral GC

Abstract Purpose: Postoperative pancreatic fistula (POPF) is a potentially fatal complication of distal pancreatectomy (DP) but the optimal prevention method is unknown. The standard methodology for DP is to dissect the pancreas using a stapler alone. This pilot study evaluated post-DP remnant closure by stapling plus a PGA felt patch and examined the predictors of POPF. Methods: We prospectively enrolled and analyzed 26 patients scheduled for DP in which the remnants were closed with staples and a PGA felt patch. Results: Primary disease included 17 pancreatic adenocarcinomas, 3 pancreatic neuroendocrine neoplasms, 2 mucinous cystic neoplasms, 2 solid pseudopapillary neoplasms, and 2 other disorders. The mean main pancreatic duct diameter at the excision site was 2.3 mm. The mean pancreatic parenchyma thickness was 12.3 mm. The mean pancreatic dissected line was 0.5 mm to the left from the left edge of the portal vein. We observed nine biochemical leaks and the formation of nine grade B POPFs. We found significant differences in the BMI, pancreatic parenchymal thickness, and pancreatic dissection line between patients with and without POPF. Conclusion: Although stapling and applying PGA felt did not show efficacy in preventing POPF, the pancreatic dissecting line was suggested as a risk factor.

The high variability in efficacy and safety of antichagasic chemotherapy involving benznidazole (BNZ) may be due to pharmacokinetic-related factors. The study evaluated the impact of experimental acute and chronic infections by the Berenice-78 strain of Trypanosoma cruzi on the pharmacokinetics of BNZ in dogs. Twenty-seven mongrel dogs were divided into the following groups: acute infection state treated with BNZ, chronic infection state treated with BNZ, acute and chronic positive controls (not treated with BNZ), and a healthy group treated with BNZ. They were evaluated at (1) basal state, (2) during infection without treatment, for cytokines panel (IL-6, interferon γ (IFN-γ), IL-10 and tumor necrosis factor α (TNF-α)) evaluation, and (3) during BNZ steady-state levels at 10, 30, 40, and 60 days after start of treatment with oral BNZ 3.5 mg/kg b.i.d. administration, in acute and chronic T. cruzi-infection, for BNZ pharmacokinetics and cytokines panel evaluation, and (4) 30 days after BNZ treatment end for cytokines evaluation. BNZ levels in serum samples were quantified using a curve range of 0.1-100 μg/mL in plasma by high-performance liquid chromatography with diode array detection (HPLC-DAD) analysis. Pharmacokinetic parameters remained stable during treatment phases, indicating no autoinduction or inhibition. Acute infection pharmacokinetics resembled that of healthy controls. Chronic infection significantly increased C max, C ss, and AUC0-12, while decreasing Vd/F and CL/F compared to both healthy and acute groups. Notably, IL-6 levels were elevated ∼7-fold during chronic infection. These data suggest that chronic inflammatory status modulates BNZ disposition, likely via IL-6 mediated P-glycoprotein inhibition. Understanding these pharmacokinetic changes is critical for optimizing BNZ dosing strategies in Chagas disease management.

Riboswitches are non-coding RNA motifs that regulate gene expression in response to ligand binding. The glycine tandem riboswitch (GTR) contains two glycine aptamers that interact extensively, driving conformational changes in the downstream expression platform to control gene expression. Despite numerous studies, the role of glycine and RNA folding pathways in co-transcriptional regulation remains unclear. Here, we integrate single-molecule kinetic analysis, co-transcriptional RNA structure probing, and modeling to reveal that the GTR processes multiple molecular inputs sequentially, guided by polymerase pausing. Our findings elucidate its stepwise 5'-to-3' folding pathway and demonstrate how sequential glycine binding to each aptamer, K+ binding to a kink-turn, non-native folding intermediates, inter-aptamer docking driving binding site pre-organization, and modulation by transcription factor NusA collectively orchestrate co-transcriptional gene regulation. These results support a model wherein glycine binding cooperativity arises through non-equilibrium mechanisms, rather than a classical concerted model.

Detecting and treating cancer at an early stage is critical for improving patient survival, quality of life, and health system efficiency. Early diagnosis offers substantial clinical benefits, reduces the need for aggressive treatments associated with advanced disease, and lowers healthcare costs. Despite these benefits, disparities in early-stage detection persist across tumor types due to challenges in screening, public awareness, and the aggressive nature of certain cancers. While early-stage diagnosis generally offers a better prognosis than late-stage detection, disease recurrence remains a significant reality and concern. Many patients experience a relapse of cancer despite initial curative treatment, which adversely affects their survival, quality of life, and financial stability. While effective new treatments for early-stage cancers have emerged, including immunotherapy and targeted therapies, barriers to reimbursement and access persist. One challenge is the absence of mature overall survival data at the time of regulatory and reimbursement approvals for most tumor types, which can result in delayed decision-making, reduced patient access, and worse outcomes. This policy paper combines insights from clinicians, health economists, outcomes researchers, and policy experts to address gaps in early-stage cancer care and provide recommendations to enhance diagnosis rates, reduce the burden of recurrence, and optimize access to innovative treatments. Central to these recommendations is the integration of early cancer care into national cancer control plans, including robust data collection and monitoring, as well as improvements in health literacy. A key factor is the use of early clinical endpoints that measure key outcomes in addition to overall survival, providing timely insights into treatment effectiveness that can guide early regulatory and reimbursement decisions prior to reaching overall survival maturity. This paper is a call to action for relevant stakeholders to take a coordinated approach that optimizes outcomes for cancer patients by promoting early detection and treatment.

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Rifaximin treatment is associated with reduced rates of overt hepatic encephalopathy (OHE) hospitalization relative to lactulose alone. This real-world study evaluated the impact of treatment on rehospitalizations following an initial OHE hospitalization among commercial, Medicare, and Medicaid patients treated with rifaximin±lactulose or lactulose only. Claims data from January 1, 2016, to September 30, 2023, were used to identify adults with an initial OHE hospitalization under commercial, Medicare, and/or Medicaid coverage (index date was the day following discharge). Patients were stratified into either the rifaximin cohort (±lactulose) or the lactulose-only cohort based on treatments received within 30 days following discharge. The 30-day OHE rehospitalization rate and OHE rehospitalization rate per-patient-per-year were compared between cohorts using adjusted logistic regression and negative binomial regressions, respectively. Subgroup analyses were conducted based on the timing of rifaximin treatment and adherence to treatment guidelines. The study included 7880 patients with an OHE hospitalization with commercial insurance (rifaximin: 5997; lactulose only: 1883), 4131 patients with Medicare insurance (rifaximin: 2419; lactulose only: 1712), and 2924 patients with Medicaid insurance (rifaximin: 1854; lactulose only: 1070). After adjustment, rifaximin was associated with a lower risk of 30-day OHE rehospitalization and lower OHE rehospitalization rates per-patient-per-year than lactulose in commercial (OR=1.75, incidence rate ratio [IRR]=1.67, respectively), Medicare (OR=1.61, IRR=1.51), and Medicaid (OR=1.50, IRR=1.54; all p<0.05) populations. Patients immediately receiving rifaximin and those with AASLD guideline-adherent escalation to rifaximin had the fewest rehospitalizations. Timely treatment with rifaximin in adherence with clinical practice guidelines following an initial OHE hospitalization was associated with improved short-term and longer-term rehospitalization outcomes, regardless of insurance type.