Long-term outcome of chronic hepatitis C virus infection in a real-world setting: The German LOTOS study.

BACKGROUND & AIMS: There are few large-scale, prospective studies comparing liver-associated events in treated and untreated patients with CHC managed in routine clinical practice. METHODS: Patients with CHC were prospectively enrolled in a non-interventional study. Data from patients with available documentation who had either achieved a sustained virological response, or were non-responders, relapsers, or had virological breakthrough following treatment with peginterferon alfa-2a±ribavirin, or who had been diagnosed but never treated at least 3 years previously, and who remained under medical observation were analyzed. Primary endpoint was liver-associated events (composite of decompensation/liver failure, ascites, hepatocellular carcinoma, or liver transplant/placement on a transplant list). RESULTS: In all, 1444 eligible patients were identified. Mean follow-up was 4.7 (standard deviation; SD 1.1) years. Patients with sustained virological response had a lower incidence of liver-associated events vs non-responders, relapsers, or virological breakthrough and never treated patients (1.7% vs 4.7% and 4.7% respectively). The proportion of patients with cirrhosis increased from baseline in the non-responders, relapsers, or virological breakthrough (6.8%-10.5%) and never treated group (3.7%-8.4%), with an associated increase in severity, but was unchanged in the sustained virological response group (2.1%). Event-free survival was significantly higher in sustained virological response patients (P=.0082). CONCLUSIONS: In this "real-world" cohort, the achievement of sustained virological response almost eliminated liver-related morbidity and mortality compared with patients who failed to achieve sustained virological response and those who were untreated. Overall, the LOTOS cohort highlights the importance of timely and effective treatment for patients with CHC.

Prevention of episodic migraines with topiramate: results from a non-interventional study in a general practice setting.

The majority of patients with migraine headaches are treated in non-specialized institutions though data on treatment outcomes are largely derived from tertiary care centers. The current non-interventional study explores efficacy and tolerability outcomes of patients with episodic migraines receiving topiramate as preventive agent in a general practice setting. A total of 366 patients (87% female, mean age 41.8 +/- 11.6 years) were eligible for migraine prevention and treated with flexible dose topiramate for 6 months (core phase), and optionally for a total of 12 months (follow-up phase). Overall, 261 patients (77.7% of safety analysis set, SAF) completed the core phase. Reasons for discontinuation included adverse events (2.1%), lost to follow-up (1.8%), other reasons (1.5%), and end of therapy (0.3%) though in the majority of patients who discontinued no reasons were listed. The median daily dose at endpoint was 50 mg/day (range, 25-187.5 mg/day). The median days with migraine headaches decreased from 6.0 to 1.2 days (p < 0.001), median pain intensity score decreased from 17.0 to 3.2 points (p < 0.001). In women with reported menstruation-associated migraine, the median number of migraine attacks decreased from 4.0 to 0.9 (p < 0.001). Absenteeism as well as triptan use decreased significantly, and significant improvements in activities of daily living and quality of life were reported. The most frequently reported AEs were paraesthesia (4.2%) and nausea (3%). Results suggest that migraine prevention with topiramate in a general practice is generally well tolerated and associated with a significant improvement in migraine headaches and related functional impairment.

Predictive factors for sustained virological response after treatment with pegylated interferon α-2a and ribavirin in patients infected with HCV genotypes 2 and 3.

BACKGROUND: Previous trials have often defined genotype 2 and 3 patients as an "easy to treat" group and guidelines recommend similar management. AIMS: The present study looks for differences between the two genotypes and analyzes predictive factors for SVR. METHODS: Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012. RESULTS: When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR predicted SVR. In genotype 3 age ≤45 years, cholesterol>130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis. CONCLUSIONS: The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis. TRIAL REGISTRATION: Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany ML21645 ClinicalTrials.gov NCT02106156.