No abstract

Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs and reduce its administration frequency. Here, we evaluated the enzymatic activity of rhDNase conjugated to a two-arm 40 kDa polyethylene glycol (PEG40) in CF sputa. Rheology data indicated that both rhDNase and PEG40-rhDNase presented similar mucolytic activity in CF sputa, independently of the purulence of the sputum samples as well as of their DNA, actin and ions contents. The macroscopic appearance of the samples correlated with the DNA content of the sputa: the more purulent the sample, the higher the DNA concentration. Finally, quantification of the enzymes in CF sputa following rheology measurement suggests that PEGylation largely increases the stability of rhDNase in CF respiratory secretions, since 24-fold more PEG40-rhDNase than rhDNase was recovered from the samples. The present results are considered positive and provide support to the continuation of the research on a long acting version of rhDNase to treat CF lung disease.

which provided monthly EQ-5D measures, treatment duration, adverse events (diarrhoea) and responder status (abdominal pain/discomfort improvement ≥ 30% from baseline). Belgian EQ-5D tariffs were used to estimate utilities and trapezoidal rule to estimate QALYs. A Delphi panel including 6 general practitioners and 5 gastroenterologists provided the resource use for IBS-C patients in different treatment phases: controlled with 2 nd line or new drug else non-responders. Patient-level costs were applied using first-order Monte-Carlo simulation (gamma distribution function; per treatment arm and responder status; health care payer perspective). A stopping rule was implemented at 4 weeks for linaclotide non-responders. A non-parametric bootstrap with 1000 replications was performed. The 2012 Belgian GDP per capita (€ 34,000) was used as willingness-to-pay threshold. Results: The responder rate at 4 weeks was 54.6% with linaclotide vs. 35.5% with SoC. There was on average 0.0129 QALYs gained per linaclotide patient vs SoC at 6 months (0.385 vs. 0.372), with an incremental cost of € 95 (€ 1,376 vs. € 1,280). The incremental cost-effectiveness ratio of was € 7,364/QALY. The diarrhoea costs were higher with linaclotide (+€ 19.4) while savings were observed in clinical management (-€ 132.2) compared to SoC. Using a willingness-to-pay threshold of € 34,000/QALY, 66% of the simulations were cost-effective. ConClusions: Due to improvements in abdominal pain/discomfort complaints in patients receiving linaclotide, savings were generated in the clinical management of IBS-C compared to SoC. Using the GDP per capita as willingness-to-pay threshold, linaclotide seems a cost-effective alternative to today SoC of IBS-C in Belgium. PGI34 Cost-EffECtIvEnEss of CaPsulE EndosCoPy (PIllCam®) In thE dIaGnosIs of small BowEl Crohn's dIsEasE

A4991.25 hospitalizations. Diagnostic tests were also more frequent (rectosigmoidoscopy: 49.3%; abdominal echography: 43.6%) except thyroid function (70.0%). The annual cost of second line was € 2,114 [1,509;2,819] versus € 2,920 [2,072;3,917] after second line failure. Hospitalizations accounted for about 75% of the costs. ConClusions: IBS with constipation leads to significant resource use and high costs certainly in case of second line treatment failure.