Syneos Health (formerly InVentiv Health Incorporated and INC Research) is a NASDAQ listed American multinational contract research organization based in Morrisville, North Carolina. The company specializes in helping companies with late-stage clinical trials. In January 2018 INC Research acquired inVentiv Health, the parent company of a subsidiary, Syneos, and the resulting company was named Syneos Health.
INTRODUCTION:Factors associated with decline of hepatic function and increase in portal-systemic shunting, which herald clinical outcome in persons with compensated cirrhosis, are poorly characterized. We used cholate challenge to evaluate the associations of liver disease etiology, concomitant diabetes, and maintenance drug therapy, with the degree of hepatic dysfunction and portal-systemic shunting.METHODS:In the SHUNT-V study, there were 255 subjects with compensated (Child-Pugh class A) cirrhosis who underwent cholate challenge, involving oral administration of [2,2,4,4-2H] cholate and measurement of its serum concentrations at 20 and 60 minutes. Test outputs included a disease severity index (DSI) to assess global liver function and SHUNT% to assess portal systemic shunting.RESULTS:Eighty-seven percent of subjects were overweight, 65% were obese, 48% had metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), 51% had type 2 diabetes mellitus, 49% were taking anti-diabetic drugs, and 45% were taking lipid-lowering drugs. Laboratory values and clinical scores of MASLD/MASH subjects were similar to subjects with other etiologies for liver disease. In univariable regression, MASLD/MASH, diabetes mellitus, metformin, and statins were associated with lower DSI and SHUNT%. In multivariable regression, lower DSI was attributable to statins (P = 0.0354) and metformin (P = 0.0561). The combined use of lipid-lowering and anti-diabetic drugs, compared with no use, was associated with 19% reduction in DSI.CONCLUSION:Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%).
Continuous proportions measured on the same experimental unit often pose two challenges: influential interior extremes that inflate variance beyond the beta ceiling and residual dependence that invalidates independent-margin models. We introduce a Bayesian copula modeling approach that combines rectangular-beta margins, which temper influential interior extremes by reallocating mass from the peak to a uniform component, with a single-parameter copula to capture concordance. Gaussian, Gumbel, and Clayton copula families are fitted, and log marginal likelihoods are obtained via bridge sampling to guide model selection. Applied to two surveys 13 years apart (2003 and 2016) of Azorella selago cushion plants on sub-Antarctic Marion Island, the copula models outperform independence baselines in explaining percent dead stem cover. Accounting for between-year dependence reveals a positive west-slope effect and weakens the cushion size effect. Simulation results show negligible bias and near-nominal 95
Background: Lenalidomide is an immunomodulatory agent thought to inhibit the growth of del(5q) haematopoietic progenitors in myelodysplastic syndromes (MDS) that was approved for use in Europe for certain forms of these conditions in 2013.Objectives: This study aimed to identify the distribution of lenalidomide treatment and safety outcomes in patients with MDS in Europe among those treated within (on-label) and outside (off-label) of the European Commission-approved indication.Design: This observational, retrospective study of prospectively collected disease registry data (13 June 2013 to 1 May 2023) summarised lenalidomide treatment patterns and safety outcomes by on- and off-label treatment in 11 European countries.Methods: Safety outcomes included progression to acute myeloid leukaemia (AML), second primary malignancies (SPMs), adverse events (AEs) and all-cause mortality. Hazard ratios (HRs) and 95% CI were reported for progression to AML comparing on- to off-label treatment.Results: Among 523 qualifying patients, more were prescribed lenalidomide off-label (n = 345) than on-label (n = 157); label status was unknown in 21 patients prescribed lenalidomide. Progression to AML occurred in 10.2% of on-label patients and 13.0% of off-label patients (HR: 0.9; 95% CI: 0.4, 1.7). Solid tumours were the most common SPM (7.0% on-label, 1.7% off-label). Neutropenia (38.9% on-label, 33.3% off-label) and thrombocytopenia (36.9% on-label, 28.1% off-label) were the most common AEs. Death occurred in 53 on-label and 75 off-label patients. The most common causes of death were unknown (19.1% on-label, 4.3% off-label) or due to AML (3.2% on-label, 6.1% off-label).Conclusion: Analysis of real-world registry data indicated that off-label lenalidomide use in patients treated for MDS was common. Across the registries studied, the overall incidence of safety events of lenalidomide in patients with MDS was consistent in both on-label and off-label use, highlighting the importance of researching off-label use of lenalidomide in MDS.Trial registration: This study was registered with the EU Post-Authorisation Studies (PAS) Register: EUPAS22604.
Two years of adjuvant abemaciclib plus endocrine therapy is approved and guideline-recommended in patients (pts) with HR+, HER2-, node-positive, early breast cancer (EBC) at high risk of recurrence. In initial real-world studies, the high rate (>85%) of treatment (tx) persistence beyond 3 months suggests that adjuvant abemaciclib is well-tolerated in routine clinical practice.1,2 Dose reductions were associated with higher persistence in prior studies and clinical trial data have shown that efficacy of abemaciclib was maintained with dose reductions. This study describes 6-month tx persistence and dosing patterns in pts with HR+, HER2-, node-positive EBC initiating abemaciclib 150 mg twice daily (BID). Retrospective data were accessed from the US de-identified Flatiron Health Research Database. Adults with HR+, HER2-, node-positive, EBC, who initiated abemaciclib 150 mg BID from Jan 2022-Jun 2024 were eligible and further characterized by ≥1 vs no dose reduction. Data cut-off was Dec 2024. Persistence rate was the proportion of pts on abemaciclib >6 months, allowing for ≤60-day medication gap within this period. Time to dose modifications and reasons for discontinuation (DC) were summarized. Subgroup analyses were conducted in pts confirmed as meeting the monarchE high-risk criteria (N2, N3, or N1 plus Grade 3 and/or tumor >5 cm). All analyses were descriptive. Of 1063 eligible pts, median age was 56 years (IQR 47, 65). Most had N1 (48%) or N2 (34%) disease. Median follow-up was 17.5 months (IQR 11, 25). Tx persistence at 6 months was 75%. DC was mostly due to adverse events (AEs; 19%) and <1% due to recurrence. Approximately 50% of pts had ≥1 dose reduction. Persistence was 85% in pts with ≥1 dose reduction and 64% in pts with no dose reductions. 70% of pts who DC’d by 6 months did not have a dose reduction. Median time from start of abemaciclib to first dose change and/or hold was 49 days (IQR 23, 111). During the first 30 days of tx and Days 31-90, DCs due to AEs were lower in pts with dose reductions vs pts with no dose reductions (Table). Persistence and use of dose reductions were similar in pts confirmed as meeting the monarchE high-risk criteria. In US clinical practice, a majority (75%) who initiated adjuvant abemaciclib continued abemaciclib beyond 6 months. Tx persistence was higher among pts with dose reductions relative to those with no dose reductions, and rates of early DCs due to AEs were low in pts with dose reductions. Given that dose reductions in monarchE were not associated with reduced efficacy, these additional real-world data support the use of early dose modifications to improve tolerability and tx persistence for adjuvant abemaciclib in pts with high risk of recurrence. H. Soliman, S. Dent, A. Liepa, V. Stefaniak, M. Huang, T. Sugihara, K. Moreira, K. Hudson, M. Goetz. Treatment Persistence and Dose Modifications in US Patients with HR+, HER2-, Node-Positive, Early Breast Cancer Treated with Adjuvant Abemaciclib [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-09.
Importance Overweight and obesity affect 60% to 78% of patients with psoriasis, affecting disease severity, treatment response, and clinical outcomes. However, no large, randomized, active-controlled clinical trial has evaluated a treatment strategy that addresses both diseases simultaneously. Objective To evaluate the efficacy and safety of ixekizumab with or without tirzepatide in participants with psoriasis and overweight or obesity. Design, Setting, and Participants This phase 3b, randomized, open-label, 52-week clinical trial was conducted at 72 sites in the US in adults with moderate to severe plaque psoriasis who have overweight with 1 or more weight-related comorbidities or obesity. The trial started on September 30, 2024, and completed the week 36 primary end point on January 8, 2026. Data were analyzed from January to February 2026. Interventions Participants were randomized (1:1) to ixekizumab plus tirzepatide or ixekizumab as adjunct to diet and exercise in both treatment arms. Main Outcomes and Measures At week 36, the primary end point was simultaneous achievement of Psoriasis Activity and Severity Index (PASI) 100 and 10% or greater weight reduction. Key secondary end points were PASI 100 and simultaneous PASI 75 and 5% or greater weight reduction, as well as 10% or greater weight reduction. Results Among the 274 randomized participants (mean [SD] age, 45.6 [12.7] years; 123 [44.9%] women and 151 [55.1%] men; mean [SD] screening body mass index [calculated as weight in kilograms divided by height in meters squared], 39.2 [9.1]; mean [SD] duration of psoriasis, 14.6 [13.0] years; mean [SD] PASI, 19.7 [8.1]), 231 (84.3%) completed the treatment through week 36. Overall, 27.1% of participants simultaneously achieved PASI 100 and a 10% or greater weight reduction with ixekizumab plus tirzepatide vs 5.8% with ixekizumab (risk difference [RD], 21.2%; 95% CI, 12.8%-29.7%; P < .001). Also, 40.6% vs 29.0% of participants achieved PASI 100 (RD, 11.6%; 95% CI, 0.3%-22.9%; P = .04), 79.9% vs 17.9% simultaneously achieved PASI 75 and a 5% or greater weight reduction (RD, 62.0%; 95% CI, 51.7%-72.2%; P < .001), and 69.2% vs 9.1% achieved a 10% or greater weight reduction (RD, 60.0%; 95% CI, 50.4%-69.7%; P < .001), respectively. Adverse events were generally consistent with established drug safety profiles, the most common being gastrointestinal tract events and injection site reactions. Gastrointestinal tract events occurred more frequently with ixekizumab plus tirzepatide vs ixekizumab. Conclusions and Relevance The trial results suggest that concomitant ixekizumab and tirzepatide produced clinically meaningful, statistically significant improvements in skin clearance and reductions in weight in participants with moderate to severe psoriasis, with no new safety concerns, while providing additional cardiometabolic benefits and a potential to elevate care. Trial Registration ClinicalTrials.gov Identifier: NCT06588283
