G González de la Fuente

4CPS-212 Relationship between ugt1a1*28 and serum bilirubin levels

Background UGT1A1 polymorphisms have been relatated to interindividual variability effectiveness and toxicity in many drugs. In addition, the presence of mutated alleles in this gene has also been identified historically as Gilbert’s disease which exhibits high levels of unconjugated bilirubin. Purpose Analysing the relationship between total serum bilirubin levels and rs8175347 (*28) polymorphism in the UGT1A1 gene. Material and methods Observational, retrospective and unicentre study of 2 years was carried out. Patients with colorectal cancer who have been tested for gDNA determination of UGT1A1 genotype for clinical practice were included. Clinical data were obtained using the application SAP®. A high level of total-bilirrubine was considered as at least a 90% determination, with total-bilirubin higher than 1 mg/dL. Polymorphism *28 of UGT1A1 was established by analysing the genomic DNA of a peripheral blood sample. Genetic characterisation was carried out using the LightClycler® 480 platform and specific allele HybProbe fluorescent probes. The relationship between the UGT1A1 genotype and levels of total serum bilirrubine were determined by univariable statistical analysis. Patients were requested to sign an informed consent form prior to the inclusion. Results One hundred and seventy-three patients were included in the study, with a median age of 62 years (81–27) and 62.3% were males. 46,2% of participants had WT genotype: 21.2% (n=17) of them showed high levels of total serum bilirubin. On the other hand, 53.7% of patients had mutant alleles (*1/*28. *28/28), of which 36.5% (n=34) showed high levels of bilirubin (p=0.003). Conclusion Our results show that the presence of *28 allele in UGT1A1 is associated with high levels of serum bilirubin. With these results, we feel that this finding could provide the clinician with a tool to detect patients with high risk of drug toxicity such as irinotecan or pazopanib, among others. No conflict of interest

OHP-005 Carbapenem restriction and its long term effectivness in an intensive care unit

This abstract was published in error and withdrawn at the author’s request.

PKP-005 Determination of genetic polymorphisms affecting metabolism of thiopurines

Background Thiopurines are widely used in different treatments. However, exposure to this drug can cause toxicity in the patient due to polymorphisms in the gene coding NUDT15, an enzyme involved in the metabolic activity of thiopurines. Carriers of defective alleles of NUDT15 accumulate large amounts of active metabolites which can cause serious damage to DNA. Purpose To develop a methodology to identify mutations that abrogate or reduce the activity of NUDT15. In this way a more personalised therapy to the patient can be applied with associated low cost. Material and methods Genetic variants of NUDT15 that cause a decrease or absence of total enzyme activity were identified: rs116855232 (called *6), rs147390019 (*7), rs186364861 (*8) and rs554405994 (*9). Determination of polymorphisms was performed by PCR and subsequent sequencing. For this purpose, pairs of primers that flank the region of interest were designed. Given the proximity of the polymorphisms on the chromosome, each primer pair amplified a region containing two of the four polymorphisms, so only two pairs of amplification primers were designed: F:GCA TCA CTA TGA GTT TAT TAG TAG C/R:CAC CAG ATG GTT CAG ATC TTC for *6 and *7 and F:ACG CAT TAC GCA CCG C/R:GCT CAC CCG AAC TCC AGA T for *8 and *9 polymorphisms. A primer was also designed within each amplified region for sequencing: CAC TAT GAG TTT ATT AGT AGC AAG (*6 and *7) and CGC TAT GAC GGC CAG (*8 and *9) . Primer design was performed with the GeneRunner programme and with the online analysis tool Primer-Blast, to confirm the specificity of pairs of primers. Reading the chromatograms was carried out with the programme Mega. DNA extraction was performed from a drop of blood deposited on paper Whatman 9031.1 Results Regions encompassing the four polymorphisms were amplified using only two primer pairs. The yield of the reaction was optimum, allowing its subsequent sequencing. The direct costs associated with determination of four markers was €27 (€6.75 for each polymorphism). Conclusion Genotyping NUDT15 allowed individualised treatment doses, as a carrier for any of these mutations. Future studies will determine the initial dose of the drug. We wished to show a simple and economical method, accessible to any laboratory with basic equipment in molecular biology, which allows detection of mutations in patients that adversely affect the metabolism of thiopurines. References and/or acknowledgements 1. Ramos-Díaz R, et al. Cancer Chemother Pharmacol2015;75:1095–8. No conflict of interest

PP-053 Evaluation of 5 compounded formulations for the treatment of oral mucositis in cancer patients

Background Oral mucositis (OM) is a frequent complication of chemotherapy which severely affects patient quality of life. Management is generally based on topical compounded formulations. Purpose To analyse the use of our compounded formulation of Lidollanten 1% for the treatment of OM in a tertiary hospital, to describe this and four other formulations and to perform a comparative cost analysis without including professional fees. Material and methods We performed a 1 year retrospective study (January 2015–December 2015) involving all cancer patients who had used our compounded formulation during the study period. Patient data were obtained from the SAP application. Results During the study period, we dispensed 3122 Lidollanten 1% preparations for 530 patients. The cost of preparation in the hospital was €1.55/100 mL, which meant €4 823.51/year. Different formulations for the treatment of OM are shown in the table. Compounded formulation Lidollanten 1% 2 3 4 5 Components - Llanten leaves- Lidocaine- Sodium borate- Potassium chlorate- Pink honey extract- Syrup - Chlorhexidine 5%- Methylprednisolone- Mepivacaine 2%- Sodium bicarbonate- Sodium chloride- Sterile water - Mepivacaine 2%- Aluminium hydroxide- Magnesium hydroxide- Sorbitol 70%- Guar gum 1%- Nipagin- Citric acid- Peppermint oil- Sterile water - Gentamicine- Hydrocortisone- Nystatin- Lidocaine- Sodium bicarbonate- Cremophor RH 40- Xanthan gum- Sorbitol 70%- Peppermint oil- Sterile water - Sucralfate- Lidocaine- Cremophor RH 40- Sorbitol 70%- Sterile water Complexity High Low High Medium Medium Preparation time 5 hours 30 min 30 min 2 hours 30 min Storage Fridge Ambient temperature Ambient temperature Fridge Fridge Expiry time (days) 30 days 30 days 60 days 15 days 15 days Cost (100 mL) (€) 1.55 1.36 4.27 6.51 2.53 Conclusion According to our data, the least expensive formulation (from the point of view of acquisition cost) was No 2, which also happened to be that requiring the least processing time; it can be stored at room temperature, with an expiry time of 1 month. For these reasons, we believe it is the most efficient. Future studies will determine whether there are differences in effectiveness between the different formulations. References and/or acknowledgements 1. Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer2014;120:1453–61. No conflict of interest

CP-098 Is the combination daptomycin-cloxacilin associated with better prognosis in methicillin susceptible staphylococcus aureus bacteraemia compared with cloxacilin monotherapy?

Background Methicillin susceptible Staphylococcus aureus (MSSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. Purpose To evaluate if the combination of daptomycin plus cloxacilin achieves higher clinical success rates in the treatment of MSSA bacteraemia than cloxacilin alone. Material and methods A single centre, retrospective, observational, comparative study was performed between January 2015 and August 2015. The subjects were patients with MSSA bacteraemia who received cloxacilin as monotherapy (standard therapy group) or the combination cloxacilin plus daptomycin. A revision of the clinical history of each patient was carried out to asses clinical, laboratoy and microbiological data. The main outcome variable was 30 day all-cause mortality and 30 day all-cause hospital readmission. Secondary endpoints were: (i) percentage of patients who achieved a decrease in CRP levels to <50% of their initial value in the first 72 h of therapy; (ii) length of hospital stay (LOS); and (iii) percentage of patients with persistent bacteraemia after 72 h of initiation of therapy. Results 14 patients met the study criteria. 7 (50%) patients received cloxacilin as monotherapy and 7 (50%) received the combination cloxacilin-daptomycin. No differences in 30 day all-cause mortality were observed (14% (1/7 in the standard therapy group vs 14% (1/7) in the combination group). No statistical differences between groups were observed in all-cause readmission at 30 days (14% (1/7) in the standard group vs 0/7 in the combination group (p = 0.337)). Similarly, there were no differences in the secondary endpoints: LOS (median 32 vs 37 days, p = 0.86) and a decrease in CRP levels to <50% of their initial value in the first 72 h of therapy (42% (3/7) in the combination group vs 28% (2/7) in the standard therapy group (p = 0.611)). The rate of persistent bacteraemia did not differ between the two groups. Conclusion Our data showed a benefit of adding daptomycin to cloxacilin in patients with MSSA bacteraemia. However, studies with a large number of patients are required to define the role of combination therapy in patients with MSSA bacteraemia. References and/or Acknowledgements Emerg Infect Dis 2011;17:1099-102 No conflict of interest.

CP-080 Comparative effectiveness of ustekinumab and adalimumab in psoriasis patients previously treated with etanercept

Background Adalimumab and ustekinumab have demonstrated a high level of efficacy in the treatment of moderate-severe psoriasis in randomised controlled trials. There are, however, no data available on the comparative effectiveness of ustekinumab and adalimumab in psoriasis patients switching from etanercept. Purpose To evaluate the comparative effectiveness of adalimumab and ustekinumab in patients previously treated with etanercept. Material and methods A single centre, retrospective, observational, comparative study was carried out from 1 November 2011 to 31 March 2013, with a follow-up of 2 years. Subjects were patients with moderate-severe psoriasis that after etanercept therapy were treated with adalimumab or ustekinumab. A revision of each patient’s clinical history was carried out to asses clinical data. The primary analysis compared the percentages of patients in each treatment group who achieved ≥75% improvement from baseline PASI score (PASI 75) at week 12. Secondary endpoints included the percentages of patients with PASI 75 at week 96. Statistical analysis was performed with the SPSS 22 software. Results 28 psoriasis patients were included: 11 (39.3%) patients received adalimumab and 17 (60.7%) received ustekinumab as secondline therapy. Median age in the adalimumab and ustekinumab groups were 58 (SD 6.5) years and 49 years (SD 16.3), respectively (p = 00.08). After 12 weeks of study treatment, 76.5% of ustekinumab treated patients (13/17) achieved a PASI 75 response compared with 36.4% (4/11) in the adalimumab group (p = 0.034). At week 96, more patients had a PASI 75 in the ustekinumab group compared with the adalimumab group, but the difference was not statistically significant (70.6% vs 36.4%, p = 0.07). Conclusion Previously studies have shown that adalimumab and ustekinumab are effective after anti-TNF inhibitor therapy. However, to our knowledge, the present study is the first to evaluate the comparative effectiveness of ustekinumab and adalimumab in psoriasis patients switching from etanercept. Our study suggests that ustekinumab is associated with a higher effectiveness compared with adalimumab as secondline treatment in patients previously treated with etanercept. Prospective, randomised studies with a large number of patients are required to establish the optimal treatment in psoriasis patients who have previously received etanercept. References and/or Acknowledgements J Dermatolog Treat 2015;26:217-22 J Eur Acad Dermatol Venereol 2011;25:1037-40 No conflict of interest.

OHP-037 Financial impact of simplifying antiretroviral therapy in hiv patients

Background In recent years, simplification of antiretroviral therapy is increasingly being recognised as an attractive therapeutic alternative for cost minimization. Currently, this kind of treatment is used in patients without a prior history of failure of protease inhibitors (PIs), with an undetectable viral load for the last 6 months and signs or symptoms of toxicity from nucleoside analogues. Purpose To describe the cost savings that have been achieved by changing triple therapy in antiretroviral treatment to monotherapy with a protease inhibitor (PI) boosted with ritonavir in HIV patients. Material and methods Cross-sectional study in which all patients who were on antiretroviral monotherapy on a particular date (1 March 2014) were included. The following variables obtained from the SAP application were recorded: the current and previous treatment, as well as the duration of each of the schemes. The prices of antiretroviral drugs used were those for which the Pharmacy Department had acquired them. Results A total of 953 patients were on antiretroviral treatment on 1 March 2014, 33 of whom were prescribed monotherapy boosted with ritonavir; 21 with darunavir/ritonavir and 12 with lopinavir/ritonavir. Median duration of treatment was 23 months (standard deviation (SD) = 18.69). The treatment simplification in these patients has meant savings of €263.000 (monthly average of €286 per patient (SD = €156)). The simplifications that showed higher rates of reduction of direct acquisition costs of the drugs were the switching of atazanavir/ritonavir+ tenofovir + abacavir for darunavir/ritonavir (−55% (€449/month/patient)), and atazanavir/ritonavir + tenofovir+ efavirenz for lopinavir/ritonavir (−52% (€446/month/patient)). Conclusion Simplification of antiretroviral therapy translates to an average monthly saving of 290 euros per patient, which has meant savings of €260,000 euros in comparison to the previous treatment these 33 patients had received. It is necessary to carry out more studies to corroborate that simplified antiretroviral therapy is, besides being financially attractive, a strategy as effective as traditional antiretroviral therapy. References and/or acknowledgements No conflict of interest.Background In recent years, simplification of antiretroviral therapy is increasingly being recognised as an attractive therapeutic alternative for cost minimization. Currently, this kind of treatment is used in patients without a prior history of failure of protease inhibitors (PIs), with an undetectable viral load for the last 6 months and signs or symptoms of toxicity from nucleoside analogues. Purpose To describe the cost savings that have been achieved by changing triple therapy in antiretroviral treatment to monotherapy with a protease inhibitor (PI) boosted with ritonavir in HIV patients. Material and methods Cross-sectional study in which all patients who were on antiretroviral monotherapy on a particular date (1 March 2014) were included. The following variables obtained from the SAP application were recorded: the current and previous treatment, as well as the duration of each of the schemes. The prices of antiretroviral drugs used were those for which the Pharmacy Department had acquired them. Results A total of 953 patients were on antiretroviral treatment on 1 March 2014, 33 of whom were prescribed monotherapy boosted with ritonavir; 21 with darunavir/ritonavir and 12 with lopinavir/ritonavir. Median duration of treatment was 23 months (standard deviation (SD) = 18.69). The treatment simplification in these patients has meant savings of €263.000 (monthly average of €286 per patient (SD = €156)). The simplifications that showed higher rates of reduction of direct acquisition costs of the drugs were the switching of atazanavir/ritonavir+ tenofovir + abacavir for darunavir/ritonavir (−55% (€449/month/patient)), and atazanavir/ritonavir + tenofovir+ efavirenz for lopinavir/ritonavir (−52% (€446/month/patient)). Conclusion Simplification of antiretroviral therapy translates to an average monthly saving of 290 euros per patient, which has meant savings of €260,000 euros in comparison to the previous treatment these 33 patients had received. It is necessary to carry out more studies to corroborate that simplified antiretroviral therapy is, besides being financially attractive, a strategy as effective as traditional antiretroviral therapy. References and/or acknowledgements No conflict of interest.

DI-089 Effectiveness of abiraterone in prostate cancer in clinical practice

Background Abiraterone is an expensive drug used in hospitals for metastatic prostate cancer and it is necessary to evaluate health outcomes from its use to establish whether it is cost-effective treatment. Purpose To analyse the effectiveness profile of abiraterone for metastatic prostate cancer in a tertiary hospital. Material and methods Retrospective observational study of three years, since abiraterone was first marketed to the present (November 2011–July 2014). All prostate cancer patients treated with abiraterone were included. Variables recorded: age, performance status (ECOG) and progression-free survival (PFS). Data were collected from patients medical records. The statistical analysis was ANOVA followed by t test. A confidence limit of p < 0.05 was set for the interpretation of results. Results 33 patients were included in the study. The median age was 72.7 (SD 9.1) years old. The PFS was 7.0 (5.2–8.8) vs. 2.9 (0.7–5.1) months for patients with ECOG 0–1 and ECOG2 respectively (p = 0.01). 5 patients were treated in first line, 3.8 months of PFS (9.1 months for ECOG0–1 patients and 1.0 months for ECOG2 patients). 28 patients in second line, 4.2 months of PFS (5.0 months for ECOG0–1 patients and 2.6 months for ECOG2 patients). Conclusion Our results indicate that ECOG 2 patients derive little clinical benefit from abiraterone. References and/or acknowledgements To the oncology service. No conflict of interest.