No abstract

To assess efficacy and safety of dornase alfa in the treatment of cystic fibrosis (CF) in children and adults. METHODS: Systematic review of Medline, Em-Base, CENTRAL and clinicaltrials.gov databases was conducted. The references from relevant articles and abstracts from conferences were also examined to identify any additional studies. Each full-text article was critically appraised with use of the Jadad Scale. Clinical practice and CF treatment procedures in Poland were consulted with clinical experts. Placebo and treatment without dornase were identified as potential comparators. Changes in FEV 1 , FVC, and FEF 25%-75% , exacerbation of respiratory symptoms, body mass change, use of drugs, number of days spent at home due to CF, hospitalizations (number and length), ambulatory visits, quality of life, mortality rate, treatment acceptance by patient and safety were assessed and compared based on the review results. RESULTS: Among 294 reports found, 17 publications concerning 12 randomized clinical trials were included in the analysis. The meta-analysis of available data regarding changes in FEV 1 after 1, 3, 6 months and 1 and 2 years showed better results with dornase therapy. The use of dornase also improved pulmonary function measured in FVC. Exacerbations of respiratory symptoms were less frequent (by 20% when dornase alpha was administered once daily and by 34% when administered twice daily), which resulted in fewer hospitalizations. Patients treated with dornase required less frequent courses of intravenous antibiotics and spent fewer days at home due to CF. Safety analysis showed a higher risk of rash, voice alteration and pharyngitis with dornase. Mortality was similar among groups. CONCLUSIONS: Dornase alfa is an effective (improves respiratory function, reduces CF symptoms, dyspnea and respiratory system exacerbations) and safe therapeutic option.

Introduction. This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR).Clinical rationale for the study. Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) -an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. Material and methods.A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied.Results. Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data -HR (95% Crl -Bayesian Credibility Interval) vs.