Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study.

BACKGROUND: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. METHODS: This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test. RESULTS: The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). CONCLUSION: Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.

Randomised multicenter phase II study of two schedules of docetaxel and gemcitabine or cisplatin/gemcitabine followed by docetaxel as first line treatment for advanced non-small cell lung cancer.

BACKGROUND: In the attempt to optimize the efficacy of chemotherapy in advanced non-small cell lung cancer (NSCLC) several strategies need to be investigated including the use of non-platinum combinations and the sequential use of different agents. PATIENTS AND METHODS: In a phase II randomised study 165 patients with stage IIIB or IV NSCLC were assigned to receive docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8 every 21 days (arm A, N=54) or docetaxel 50 mg/m(2) days 1 and 15 plus gemcitabine 1600 mg/m(2) days 1 and 15 every 28 days (arm B, N=57) or gemcitabine 1200 mg/m(2) days 1 and 8 plus cisplatin 100mg/m(2) day 2 every 21 days for 3 cycles followed by docetaxel 75 mg/m(2) day 1 every 21 days for 3 cycles (arm C, N=54). The primary endpoint of the trial was overall response rate. Secondary end points included safety, progression-free and overall survival. RESULTS: Response rate was 22.2%, 23.2% and 33.3% after 3 cycles, whereas at the end of treatment was 24.1%, 12.5% and 27.8% in arm A-C, respectively. Median time to progression was similar in all the 3 arms: 6.7 months in arm A (95% CI: 4.8-9.7), 5.6 in arm B (5.0-7.9) and 6.6 in arm C (5.7-9.1). The median survival time was 10.7 months in arm A (95% CI: 6.8-15.6), 8.9 in arm B (7.4-12.5) and 14.6 in arm C (8.0-22.4) and 1-year survival rate was 46.3%, 37.9% and 53.9%, respectively. Grade 3-4 haematological toxicities were more frequent in arm C while non-haematological were more common in the gemcitabine and docetaxel arms. CONCLUSIONS: The results of this phase II randomised clinical trial do not indicate a clear superior efficacy of one of the tested combinations according to the planned statistical design and none of these regimens is sufficiently active or less toxic to warrant further investigation in a phase III study.

Left ventricular diastolic dysfunction in elderly hypertensives: results of the APROS-diadys study.

BACKGROUND: A number of patients with chronic heart failure (CHF) have diastolic but not systolic dysfunction. This occurs particularly in the elderly and in hypertension, but the prevalence of diastolic dysfunction in elderly hypertensives without CHF has never been investigated systematically. METHODS AND RESULTS: The Assessment of PRevalence Observational Study of Diastolic Dysfunction (APROS-diadys) project was a cross-sectional observational study on elderly (age >/= 65 years) hypertensives without systolic dysfunction [left ventricular ejection fraction (LVEF) >/= 45%] consecutively attending hospital outpatient clinics in Italy, in order to establish the prevalence of echocardiographic signs of diastolic dysfunction according to various criteria, and to correlate them with a number of demographic and clinical characteristics. Primary criteria for diastolic dysfunction was an E/A ratio (ratio between transmitral peak velocities of E and A waves) < 0.7 or > 1.5 on echocardiographic Doppler examination. Secondary criteria were: E/A < 0.5 and deceleration time (DT) > 280 ms, or isovolumic relaxation time (IVRT) > 105 ms or pulmonary vein (PV) peak systolic/peak diastolic flow (S/D) ratio > 2.5 or PV atrial retrograde flow (PV A) > 35 cm/s. Throughout Italy, 27 447 patients were screened in 107 clinics, with 24 141 excluded according to protocol. Among the remaining 3336 patients, 754 (22.6%) had signs of CHF. After exclusion of 37 protocol violators, 2545 patients (49.0% men, mean age 70.3 years, 95.4% under antihypertensive treatment) were studied ultrasonographically. Diastolic dysfunction (primary criteria) was found in 649 (25.8%) patients. Multiple logistic regression analysis found age, gender, left ventricular mass, systolic and pulse pressures and midwall shortening fraction as significant covariates. Using secondary criteria, the prevalence of diastolic dysfunction was higher (45.6%), mostly because of IVRT > 105 ms or PVA flow > 35 cm/s. CONCLUSION: CHF and diastolic dysfunction are highly prevalent in elderly hypertensives attending hospital clinics.