Triple combination therapy with amlodipine, valsartan, and hydrochlorothiazide vs dual combination therapy with amlodipine and hydrochlorothiazide for stage 2 hypertensive patients

Maurizio Destro1, Nora Crikelair2, Joseph Yen2, Robert Glazer 1Azienda Ospedaliera della Provincia di Pavia, Stradella (PV), Italy; 2Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USAObjective: This post hoc analysis evaluated the efficacy and safety of triple therapy with amlodipine/valsartan+hydrochlorothiazide (Aml/Val+HCTZ) vs dual therapy with Aml+HCTZ in stage 2 hypertensive patients.Methods: The analysis included patients from an eight-week, multicenter, double-blind study, randomized to Aml/Val 10/160 mg or Aml 10 mg groups, who received add-on HCTZ 12.5 mg at week 4 if mean sitting systolic blood pressure (msSBP) was >130 mmHg.Results: Of the patients receiving Aml/Val+HCTZ and Aml+HCTZ, 98% (N = 133/136) and 96% (N = 200/208) completed the study, respectively. Baseline characteristics were similar across groups (Caucasians, 80.2%; diabetics, 14.8%; age, 58.6 years [28.2% ≥ 65 years]; body mass index, 31 kg/m2; mean sitting blood pressure (msBP), 171.5/95.5 mmHg [18% msSBP ≥ 180 mmHg]). Aml/Val+HCTZ provided significantly greater msBP reductions from baseline to week 8 than Aml+HCTZ (30.5/13.8 vs 24.3/8.3 mmHg, P < 0.0001). The incremental msBP reduction (week 4 to 8) with HCTZ added to Aml/Val was greater than when added to Aml (6.9/3.5 vs 3.1/1.0 mmHg, P < 0.01). Treatments were well tolerated with similar overall incidence of adverse events (Aml/Val+HCTZ: 33.8%, Aml+HCTZ: 33.2%).Conclusion: Aml/Val+HCTZ provided significantly greater BP reductions than Aml+HCTZ in patients with stage 2 hypertension. Aml/Val+HCTZ triple therapy may be a suitable option for patients requiring more than two agents to reach target BP.Keywords: amlodipine, valsartan, stage 2 hypertension, HCTZ, triple therap

Impact of dupilumab across seasons in patients with type 2, uncontrolled, moderate-to-severe asthma

Medical writing/editorial assistance was provided by Natalia Crespo, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guideline s.Background: Seasonal variability could influence asthma exacerbations. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation. In the 52-week QUEST study (NCT02414854), add-on dupilumab every 2 weeks vs placebo significantly reduced exacerbations and improved prebronchodilator forced expiratory volume in 1 second in patients with uncontrolled, moderate-to-severe asthma. TRAVERSE (NCT02134028), the open-label QUEST extension study, enrolled patients with moderate-to-severe asthma to investigate long-term safety and efficacy of dupilumab, including patients who previously received placebo that initiated dupilumab therapy. Objective: To investigate long-term dupilumab efficacy in reducing exacerbations across yearly seasons in patients with type 2 inflammatory asthma with and without clinical evidence of allergic asthma. Methods: Unadjusted annualized exacerbation rate and proportions of patients experiencing severe asthma exacerbations are reported by month and season and for both hemispheres. Results: The proportion of patients with type 2 asthma experiencing 1 or more severe asthma exacerbations during QUEST was 20.8% vs 10.0% in spring, 18.2% vs 7.3% in summer, 22.2% vs 12.6% in autumn, and 26.4% vs 12.0% in winter, for placebo- vs dupilumab-treated patients, respectively; P was less than.001 for placebo vs dupilumab in all seasons. Reductions in the proportion of patients experiencing severe exacerbations across seasons in subgroups with and without evidence of allergic asthma were similar to the overall type 2 population. Reductions in severe exacerbations observed during QUEST were sustained during TRAVERSE, up to 96 weeks across both hemispheres. Conclusion: Dupilumab reduced asthma exacerbations, with no difference in the reduction between seasons, in patients with type 2 inflammation, with and without evidence of allergic asthma

Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA VENTURE (VENTURE) study (NCT02528214), dupilumab versus placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed. Objective: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose. Methods: The OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks versus placebo, categorized by a baseline OCS dose of less than 10 mg/d or 10 or more mg/d. Results: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose of less than 10 mg/d and 10 or more mg/d, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator forced expiratory volume in 1 second in patients in both dose groups. Conclusions: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS while also reducing exacerbations and improving lung function