Introduction Current guidelines recommend adding an oral antihyperglycemic agent (AHA) to metformin in patients with type 2 diabetes mellitus (T2DM) uncontrolled on metformin. Recent randomized clinical trials (RCTs) have demonstrated that adding dual AHAs instead of a single AHA provided more effective glycemic control. However, the comparative efficacy of approved single and dual initiation strategies is unknown. Therefore, we conducted a Bayesian network meta-analysis to compare the efficacy of dual and single add-on oral AHAs in patients uncontrolled on metformin. Methods A systematic literature review of RCTs was conducted following Cochrane and ISPOR guidelines. MEDLINE, Embase, and CENTRAL were searched from inception to November 19, 2019. Approved oral doses of sodium–glucose co-transporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in single or dual initiation therapies were indirectly compared. Outcomes focused on efficacy and included mean change from baseline in hemoglobin A1c (HbA1c), weight, systolic blood pressure (SBP), diastolic blood pressure, and achieving HbA1c target < 7% at 24–26 weeks. Fixed and random effects models with Markov chain Monte Carlo simulations were used. Results Of 1955 unique records screened, 25 RCTs (14,264 participants) were included. In patients uncontrolled on metformin, dual AHA added to metformin had statistically significant or a trend of greater reduction in HbA1c compared to single AHAs, with ertugliflozin + sitagliptin showing the greatest improvement. Statistically significant reductions in weight and SBP were observed with ertugliflozin + sitagliptin, ertugliflozin, or canagliflozin compared to single initiation DPP-4 inhibitors. Conclusion For reduction of HbA1c, weight, and SBP in patients uncontrolled on metformin, add-on dual AHAs showed greater improvement compared to single AHAs. These findings can further inform the treatment of T2DM patients uncontrolled on metformin. Supplementary Information The online version of this article (10.1007/s13300-020-00975-y) contains supplementary material, which is available to authorized users.
e20532 Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.
Background Antimicrobial resistance (AMR) is a global threat to effective prevention and treatment of an ever-increasing range of infections. Pneumococcal conjugate vaccines (PCV) used in infant national immunization programs have been shown to decrease AMR pneumococci. Cost-effectiveness models evaluating the value for money of PCV programs have not considered the economic impact of reducing antimicrobial prescribing or prolonged infections due to treatment failures. Standardized frameworks are needed for models to address outcomes and impact on health resource utilization related to AMR. Methods We developed a conceptual modeling methodology suitable for a health economic evaluation of an infant PCV program. We considered impact of PCVs on pneumococcal disease (PD) specifically related to clinical management of AMR-PD, including AMR epidemiology, antibiotic prescribing patterns, and healthcare resource utilization. Model inputs were evaluated regarding optimal and available data sources considering the complex nature of AMR at the national, regional, and global level. Results The proposed framework considers impact of PCVs on antimicrobial prescribing due to invasive pneumococcal disease (IPD), community acquired pneumonia (CAP), and acute otitis media (AOM) across 3 pathways (Figure 1). The population and pathogen-level pathway describe epidemiology and vaccine impact. The care level pathway describes clinical disease management. The health outcomes pathway characterizes resistant or successfully treated PD costs and quality of life. Conceptual Economic Model Methodology Conclusion We present a generalizable methodology to quantify impact of PCVs on cases and outcomes of PD related to AMR. Modelling vaccine-preventable burden of AMR-PD requires data extrapolations and assumptions due to the myriad of interconnected pathways (i.e. microbiology, epidemiology, environment, health systems). Further work is needed to validate assumptions and linkages across incomplete data sources. Disclosures Raymond Farkouh, PhD, Pfizer (Employee) Arianna Nevo, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Jennifer Uyei, PhD, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Cassandra Hall-Murray, PharmD, Pfizer, Inc. (Employee) Joseph Lewnard, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Advisor or Review Panel member) Matthew Wasserman, MSc., Pfizer Inc. (Employee)
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