Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis.

OBJECTIVES: Hypertension is a leading cause of death and disease burden followed by dyslipidemia. Their asymptomatic nature leads to low adherence and persistence to treatments. A systematic literature review (SLR) investigated the impact of single-pill-combinations (SPC) compared to free-equivalent combination (FEC) on adherence, persistence, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes, in patients with hypertension, dyslipidemia, or both. METHODS: MEDLINE, MEDLINE-IN-PROCESS, Embase, and Cochrane were searched from inception until 11 May 2021, for studies comparing SPC against FEC in patients with hypertension and/or dyslipidemia. Patient characteristics, study design, therapies, measures of adherence or persistence, clinical outcomes, and follow-up were extracted. RESULTS: Among 52 studies identified in the SLR, 27 (n = 346,030 patients) were included in the meta-analysis. SPCs were associated with significantly improved adherence compared with FEC, as assessed through medication-possession-ratio ≥80% (odds ratio (OR) 0.42, p < 0.01) and proportion of days covered ≥80% (OR 0.45, p < 0.01). SPC also improved persistence (OR 0.44, p < 0.01) and systolic blood pressure (SBP) reduction (mean difference -1.50, p < 0.01) compared with the FEC. CONCLUSIONS: SPC use resulted in significantly improved adherence, persistence, and SBP levels compared with FEC in patients with hypertension. The findings support SPC use in reducing the burden of hypertension and dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in the blood. Due to the silent nature of the diseases, patients can fall short of optimal medical treatment adherence and persistence, leading to poor outcomes and disease complications. Simplification of the treatment regimen can be achieved using SPC therapies. The study was conducted to look for published studies that compared the use of SPC with FEC in patients with high blood pressure, high lipid levels in the blood, or both. The researchers were able to find 52 already published studies, of which, 27 studies reported adherence, persistence, and SBP reduction which were included in the data analysis. Researchers found SPCs to be associated with much greater improved adherence and persistence and a higher reduction in SBP when compared with FEC in high blood pressure patients. These findings support SPC use in reducing the burden of high blood pressure and high lipid levels in the blood.

A Meta-Analysis of the Efficacy of Pomalidomide-Based Regimens for the Treatment of Relapsed/Refractory Multiple Myeloma After Lenalidomide Exposure.

INTRODUCTION: The objective was to assess the benefit of pomalidomide-based combination regimens in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide. A pooled estimate was obtained for efficacy outcomes including overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS) based on multiple trials conducted in this patient population. PATIENTS AND METHODS: A literature search was conducted on March 22, 2022 for relevant trials published between January 1, 2016 and the search date. The search identified 12 eligible trials with publications dated between 2016 and 2021. The meta-analyses were conducted among the intention-to-treat (ITT) population (patients treated in all lines of therapy) and 2 subpopulations: 2L (only patients treated in the second line [2L]) and ≥2L (patients treated in the 2L and beyond). RESULTS: From the meta-analyses, ORR was 69.9% for ITT, 74.4% for ≥2L, and 87.2% for 2L. CR rate was 12.1% for ITT, 17.6% for ≥2L, and 29.7% for 2L. One-year PFS rates were 55.1% for ITT, 59.1% for ≥2L, and 74.0% for 2L. Two-year PFS rates were 29.3% for ITT, 36.0% for ≥2L, and 41.9% for 2L. CONCLUSION: Pomalidomide-based combination regimens were effective in patients with RRMM previously treated with lenalidomide and tended to be associated with better outcomes when used earlier in the treatment pathway. A drug class switch may not always be necessary when making treatment decisions for patients with RRMM for whom the benefits of lenalidomide have been exhausted, although this must be supported by comparative studies.

Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis.

PURPOSE: The goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). METHODS: The efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative ranking area (SUCRA) values. Expert opinion from 2 hematologists was sought to validate results. FINDINGS: Both networks showed a significant improvement in PFS for acalabrutinib + obinutuzumab over all comparators. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B. Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax + obinutuzumab in Network B but not Network A. Although OS HRs all favored acalabrutinib, most were not significant and were characterized by wide CrIs, indicating a high level of uncertainty. Acalabrutinib + obinutuzumab ranked highest in terms of PFS improvement (SUCRA values, 98% and 100%) and OS improvement (SUCRA values, 92% and 94%), followed by acalabrutinib monotherapy (SUCRA values for PFS, 88% and 90%; OS, 83% and 87%) in Networks A and B, respectively. IMPLICATIONS: Acalabrutinib was associated with favorable PFS and OS compared with frontline CLL therapies and ranked highest in treatment efficacy over the other comparators. The NMA was limited by heterogeneity in patient baseline characteristics across trials, variable treatment regimens, and short study follow-up times. Despite these limitations, the NMA provides insights into the relative efficacy of acalabrutinib compared with frontline CLL therapies in the absence of head-to-head clinical trials.

Adverse Birth Outcomes as Indicators of Poor Fetal Growth Conditions in a French Newborn Population-A Stratified Analysis by Neighborhood Deprivation Level.

Background: Adverse birth outcomes are related to unfavorable fetal growth conditions. A latent variable, named Favorable Fetal Growth Condition (FFGC), has been defined by Bollen et al., in 2013; he showed that this FFGC latent variable mediates the effects of maternal characteristics on several birth outcomes. Objectives: The objectives of the present study were to replicate Bollen's approach in a population of newborns in Paris and to investigate the potential differential effect of the FFGC latent variable according to the neighborhood socioeconomic level. Methods: Newborn health data were available from the first birth certificate registered by the Maternal and Child Care department of the City of Paris. All newborns (2008-2011) were geocoded at the mother residential census block. Each census block was assigned a socioeconomic deprivation level. Several mothers' characteristics were collected from the birth certificates: age, parity, education and occupational status and the occupational status of the father. Three birth outcomes were considered: birth weight (BW), birth length (BL) and gestational age (GA). Results: Using a series of structural equation models, we confirm that the undirected model (that includes the FFGC latent variable) provided a better fit for the data compared with the model where parental characteristics directly affected BW, BL, and/or GA. However, the strength, the direction and statistical significance of the associations between the exogenous variables and the FFGC were different according to the neighborhood deprivation level. Conclusion: Future research should be designed to assess the how robust the FFGC latent variable is across populations and should take into account neighborhood characteristics to identify the most vulnerable group and create better design prevention policies.

Premature Adult Death and Equity Impact of a Reduction of NO2, PM10, and PM2.5 Levels in Paris-A Health Impact Assessment Study Conducted at the Census Block Level.

Background: To support environmental policies aiming to tackle air pollution, quantitative health impact assessments (HIAs) stand out as one of the best decision-making tools. However, no risk assessment studies have quantified or mapped the health and equity impact of air pollution reduction at a small spatial scale. Objectives: We developed a small-area analysis of the impact of air pollution on "premature" death among an adult population over 30 years of age to quantify and map the health and equity impact related to a reduction of air pollution. Methods: All-cause mortality data of an adult population (>30 years) from January 2004 to December 2009 were geocoded at the residential census block level in Paris. Each census block was assigned socioeconomic deprivation levels and annual average ambient concentrations of NO2, PM10, and PM2.5. HIAs were used to estimate, at a small-area level, the number of "premature" deaths associated with a hypothetical reduction of NO2, PM10, and PM2.5 exposure. In total, considering global dose response function for the three pollutants and socioeconomic deprivation specific dose response function, nine HIAs were performed for NO2 and six and four HIAs for PM10 and PM2.5, respectively. Finally, a clustering approach was used to quantify how the number of "premature" deaths could vary according to deprivation level. Results: The number of deaths attributable to NO2, PM10, and PM2.5 exposure were equal to 4301, 3209, and 2662 deaths, respectively. The most deprived census blocks always appeared as one of the groups most impacted by air pollution. Our findings showed that "premature" deaths attributable to NO2 were not randomly distributed over the study area, with a cluster of excess "premature" deaths located in the northeastern area of Paris. Discussion: This study showed the importance of stratifying an environmental burden of disease study on the socioeconomic level, in order to take into consideration the modifier effect of socioeconomic status on the air pollution-mortality relationship. In addition, we demonstrated the value of spatial analysis to guide decision-making. This shows the need for tools to support priority-setting and to guide policymakers in their choice of environmental initiatives that would maximize health gains and reduce social inequalities in health.