M. A. González Fernández

CP-153 Effectiveness of new direct acting antivirals for chronic hepatitis C

Background Recently, new direct acting antivirals (DAAs) for chronic hepatitis C have been licensed. These drugs achieve a virologic sustained response (SVR) above 90% in clinical trials. SVR is defined as undetectable HCV RNA 12 weeks after treatment completion (SVR12). Purpose To evaluate the effectiveness of treatment with new DAAs for chronic hepatitis C in real medical practice. Material and methods Observational retrospective study that included patients with chronic hepatitis C treated with new DAAs, who had finished treatment and had results for HCV RNA levels 12 weeks post-treatment. We considered that the drug was effective if the patient achieved SVR12. Data collected were: age, gender, HIV coinfection, prior treatment experience, genotype, hepatic fibrosis stage, DAA regimen and HCV RNA level. Results We included 86 patients; 66% were males. Median age was 57 years (29–84). 31 (36%) patients were HIV coinfected. Regarding previous treatment, 38 (44%) patients were naïve, 26 (30%) non-responders, 13 (15%) relapsers, 7 (8%) partial responders and 2 (2.33%) patients had no data. The most frequent genotype was 1b (62%). The hepatic fibrosis stage was F4 in 55 (64%) patients, F3 in 19 (22%), F2 in 11 (13%) and 1 (1.16%) patient had no data. The treatment regimens were: dasabuvir+paritaprevir/ritonavir+ombitasvir+ribavirine 12 weeks: 22 (25.58%) patients. sofosbuvir+ledipasvir 8–12 weeks: 22 (25.58%) patients. simeprevir+PegIFN+ribavirine 24 weeks: 5 (5.81%) patients. sofosbuvir+daclatasvir 24 weeks: 7 (8.14%) patients. sofosbuvir+daclatasvir+ribavirine 12–24 weeks: 6 (6.98%) patients. sofosbuvir+simeprevir+ribavirine: 12 weeks: 13 (15.12%) patients and 24 weeks 4 (4.65%) patients. sofosbuvir+simeprevir: 24 weeks, 4 (4.65%) and 12 weeks, 1 (1.6%) patient. sofosbuvir+ribavirine 16 weeks: 1 (1.16%) patient. paritaprevir/ritonavir+ombitasvir+ribavirine 12 weeks: 1 (1.16%) patient. 81 (94%) patients achieved RVS12. Patients did not achieve RVS12 with: sofosbuvir+daclatasvir 24 weeks (2 patients), simeprevir+PegIFN+ribavirine 24 weeks (2 patients) and dasabuvir+paritaprevir/ritonavir+ombitasvir+ribavirine 12 weeks (1 patient). Conclusion The RVS12 rate achieved with the new DAAs in this study matches the results obtained in published clinical trials. These results are very good but now we have to face the challenge of how to treat patients who have not responded to these therapies and look for possible causes, such as low adherence and resistance. References and/or Acknowledgements European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015;63:199–236 No conflict of interest.

CP-011 Pirfenidone in Idiopathic Pulmonary Fibrosis

Background The search for effective treatment in idiopathic pulmonary fibrosis (IPF) has involved numerous clinical trials without significant success. However, in 2011, pirfenidone was the first drug to be approved for the treatment of IPF in Europe. Purpose To evaluate the effectiveness and safety of pirfenidone. Materials and methods A retrospective, longitudinal, observational and descriptive study from January 2012 to April 2013. Clinical data were obtained by medical record review of 3 patients undergoing treatment with pirfenidone for twelve, thirteen and fifteen months. The main clinical variable studied was the variation of the forced vital capacity (FVC) from basal levels, considering it a positive response to the treatment if FVC didn’t decrease more than 10%. Other variables analysed were: FEV1/FVC (increased in IPF), forced expiratory volume in one second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) (both decreased in IPF). Results Two patients showed an FVC increase of 16.1% and 1.7%; in the third patient it decreased by 1.35%. FEV1 increased in all patients by 13.6%, 1.9% and 1.4%. FEV1/FVC increased in all patients by 2%, 0.26% and 2.31%. DLCO decreased in all cases at rates of: 8%, 6% and 2.4%. Adverse effects detected were: gastrointestinal disturbances and dyspepsia (3 patients), rash (2 patients), asthenia (2 patients), insomnia (1 patient), backache (1 patient), respiratory infection (1 patient), and diarrhoea (1 patient). Conclusions In patients with idiopathic pulmonary fibrosis, pirfenidone has proven to be effective on the main variable FCV and secondary variable FEV1, but not on FEV1/FVC and DLCO. Detected adverse reactions matched with those described in the literature. Despite some indications of efficacy, further studies are required to evaluate the potential benefit. No conflict of interest.Background The search for effective treatment in idiopathic pulmonary fibrosis (IPF) has involved numerous clinical trials without significant success. However, in 2011, pirfenidone was the first drug to be approved for the treatment of IPF in Europe. Purpose To evaluate the effectiveness and safety of pirfenidone. Materials and methods A retrospective, longitudinal, observational and descriptive study from January 2012 to April 2013. Clinical data were obtained by medical record review of 3 patients undergoing treatment with pirfenidone for twelve, thirteen and fifteen months. The main clinical variable studied was the variation of the forced vital capacity (FVC) from basal levels, considering it a positive response to the treatment if FVC didn’t decrease more than 10%. Other variables analysed were: FEV1/FVC (increased in IPF), forced expiratory volume in one second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) (both decreased in IPF). Results Two patients showed an FVC increase of 16.1% and 1.7%; in the third patient it decreased by 1.35%. FEV1 increased in all patients by 13.6%, 1.9% and 1.4%. FEV1/FVC increased in all patients by 2%, 0.26% and 2.31%. DLCO decreased in all cases at rates of: 8%, 6% and 2.4%. Adverse effects detected were: gastrointestinal disturbances and dyspepsia (3 patients), rash (2 patients), asthenia (2 patients), insomnia (1 patient), backache (1 patient), respiratory infection (1 patient), and diarrhoea (1 patient). Conclusions In patients with idiopathic pulmonary fibrosis, pirfenidone has proven to be effective on the main variable FCV and secondary variable FEV1, but not on FEV1/FVC and DLCO. Detected adverse reactions matched with those described in the literature. Despite some indications of efficacy, further studies are required to evaluate the potential benefit. No conflict of interest.

GRP-035 Boceprevir and Telaprevir: Safety

Background Protease inhibitors boceprevir and telaprevir were approved by the European Medicines Agency in July and September 2011 respectively for the treatment of hepatitis C genotype-1 in combination with peginterferon and ribavirin (triple therapy). Purpose To describe the safety of boceprevir and telaprevir in clinical practise. Materials and Methods All patients who received triple therapy prior to commercialization (compassionate use) with boceprevir or telaprevir to September 2012 were included. Data collected were: drugs administered for triple therapy, analytical parameters (haemoglobin, neutrophils and platelets) and subjective adverse effects. Patients were educated by the pharmacist about the medicines at the start of triple therapy and interviewed about adverse effects monthly with each refill of triple therapy. Results Of the 36 patients with chronic hepatitis C included, 16 were treated with telaprevir and 20 with boceprevir. The most frequent adverse reactions were anaemia, neutropenia and thrombocytopenia. Anaemia was managed by reducing the dose of ribavirin (7 patients), erythropoiesis-stimulating agents (11 patients) and packed cells (7 patients). Neutropenia and thrombocytopenia were controlled with peginterferon dose reduction (2 patients) and granulocyte colony-stimulating factor (4 patients). Other adverse effects were fatigue or discomfort (16 patients), insomnia (5 patients), fever (5 patients), pruritus, dysgeusia, headache, nausea, diarrhoea and irritability. Eight patients had to discontinue treatment due to adverse reactions which were not controlled with dose adjustment or supportive drugs. Conclusions All adverse events observed were reported in the EMA studies. Protease inhibitors have shown improve sustained virological response in clinical trials but these drugs are associated with a lot of adverse reactions. It is very important to have close collaboration between the physician and the pharmacist for medicines management, so that adverse reactions not described in the drug information will be reported to health agencies. Abstract GRP-035 Table 1 Protease inhibitor No. of patients Anaemia Neutropenia Thrombocytopenia n (%) Boceprevir 20 17 (85) 14 (70) 15 (75) Telaprevir 16 11 (69) 6 (38) 13 (81) No conflict of interest.