Ranibizumab for Visual Impairment due to Diabetic Macular Edema: Real-World Evidence in the Italian Population (PRIDE Study)

Purpose. An expanded access program (PRIDE study) in Italy to provide ranibizumab 0.5 mg to diabetic macular edema (DME) patients, prior to reimbursement. Methods. Open-label, prospective, phase IIIb study. Majority of patients were not treatment-naïve before enrollment. Patients received ranibizumab as per the EU label (2011). Safety was assessed by incidences of ocular/systemic adverse events (AEs) and serious AEs (SAEs) and efficacy in terms of visual acuity (VA) change from baseline (decimal score or Snellen (20/value)). Results. Overall, 515 patients (83.5%) completed the study. In unilateral/bilateral patients, commonly observed AEs were cardiac disorders (1.3%/1.3%) and nervous system disorders (1.3%/1.1%); SAEs were reported in 4.5%/4.8% of patients. Acute renal failure, lung carcinoma, and cardiac arrest were the causes of death in one unilateral and two bilateral patients. Ranibizumab improved/maintained VA (Snellen (20/value)/decimal scores) in both unilateral (up to −16.7/1.5) and bilateral patients (up to −23.6/1.2) at Month 5, with a mean of 4.15 and 4.40 injections, respectively. Overall, no difference was observed in the VA outcomes and treatment exposure between unilateral/bilateral patients. Conclusions. The PRIDE study provided early ranibizumab access to >600 Italian patients. Ranibizumab was well-tolerated and improved/maintained VA in 40.2%–68.8% patients, with no differences in case of unilateral or bilateral pathology. The study is registered with EudraCT

Clinical efficacy and safety of secukinumab in patients with psoriasis and comorbidities: pooled analysis of 4 phase 3 clinical trials

Background The influence of comorbidities on the efficacy and safety of biologic therapies in psoriasis has not been rigorously explored. Objective To assess the incremental burden of comorbidities on clinical efficacy and safety of secukinumab vs. etanercept and placebo among patients with plaque psoriasis pooled from 4 phase 3 trials. Methods Efficacy was assessed at week 12 according to achievement of Psoriasis Area and Severity Index (PASI) and Investigator’s Global Assessment (IGA; modified 2011) responses. Efficacy comparisons between treatment arms stratified by comorbidity status were made using logistic regression analysis with nonresponder imputation. Relationships between baseline characteristics and clinical responses were evaluated by χ2 tests. Results Of 2401 patients, 1469 (61.2%) had ≥1 active baseline comorbidity. Regardless of comorbidity status, patients receiving secukinumab were more likely to achieve PASI and IGA responses than those receiving etanercept or placebo at week 12 (p < .05 for all comparisons). Body weight of ≥90 kg was consistently associated with a decreased likelihood of achieving PASI and IGA responses (p < .01 for all comparisons). Safety was comparable across treatment arms stratified by comorbidity. Conclusions Secukinumab improved clinical outcomes and was well tolerated in patients with concomitant baseline comorbid conditions

Pharmacological approach and adherence to treatment recommendations in frequently and non-frequently exacerbating COPD patients from Italy: MISTRAL - The prospective cohort, observational study

Background: Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients\u2019 health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients Methods: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy. Eligible patients were divided into two cohorts based on their exacerbation history in the year prior to the enrolment, frequent exacerbators (FEs; 652 exacerbations), and non-frequent exacerbators (NFEs; 641 exacerbation). The primary objective was to assess adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs and NFEs at baseline and follow-up visits Results: Of the 1489 enrolled patients, 1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At baseline, 57.8% of patients were treated according to GOLD 2011 recommendations; a greater proportion of FEs were treated according to GOLD recommendations, compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all study visits. At baseline, GOLD group D patients were the most adherent (81.2%) to treatment recommendations, while group A patients were the least adherent (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist (LAMA) + long-acting \u3b22-agonist/inhaled corticosteroid (LABA/ICS) was the most frequent prescribed treatment at all study visits, irrespective of patient's exacerbation history. Changes in treatment were more frequent in FEs versus NFEs Conclusions: The Mistral study reports a scarce adherence to the GOLD 2011 treatment recommendations in routine clinical practice in Italy. The adherence was particularly low in less severe, non-frequent exacerbating patients mostly for ICS overuse, and was higher in high-risk, frequent exacerbating COPD patient

Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention