Gj Nazco Casariego

GRP-078 Guideline For Albumin Use: Effect on Cost Saving

Background Albumin has been widely used in clinical practise. While some of these indications are supported by the results of randomised studies, others are based only on clinical experience and have not been proved in prospective studies. Efforts should be made to define the indications for albumin use, so that patients gain the maximum benefit from its administration. Purpose To evaluate the cost saving obtained by the implementation of a guideline for albumin use in a 737-bed hospital. Materials and Methods Retrospective study that compared albumin use in two periods: July–September 2012 vs. July–September 2011. In June 2012 the guideline for albumin use was distributed to the medical staff. Physicians were requested to complete a form for each albumin order indicating the type and amount of albumin, the clinical service, and the indication for use. Albumin use data and costs were obtained from pharmacy service management system (SAP®) and were tabulated using the Excel® software. Results The total amount of albumin ordered during the study period was 29.360 g (€63,246) vs. 53.195 g (€108,617) for the same period during 2011, which means a reduction of 45%. In terms of cost, the saving obtained amounted to €45,371 (58%). The albumin use by specialty had also changed; a major decrease in use of albumin was observed for Anaesthesiology 4,000 g (75%), General Surgery 3,080 g (65%), Nephrology 4,900 g (64%), Internal Medicine 3,860 g (56%), Haematology 1,410 g (53%) and Digestive 1,400 g (30%). On the other hand, Haemodialysis significantly increased its use of albumin to 2,805 g (65%), although within the approved indication of plasmapheresis. Conclusions An albumin use guideline with restrictions focused on albumin prescriptions had suficient efficacy to reduce consumption and save cost. In our hospital guideline the cost of implementation decreased a 58% (€181,484 per year). No conflict of interest.

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

4CPS-147 Determination of tpmt and nudt15 polymorphisms in a patient with common variable immunodeficiency

Background The lack of activity in thiopurine-methyltrasnferase (TPMT) is related to severe toxicity in the use of thiopurines (azathioprine, 6-mercaptopurine and thioguanine). This lack of activity is often due to genetic polymorphisms located at TPMT, and recently demonstrated in NUDT15 genes. Purpose To describe the case of a patient with inflammatory elbow disease (IBD) and a congenital immunodeficiency who is being prescribed azathioprine and who has been tested for TPMT and NUDT15 genetic polymorphisms determination. Material and methods Male, 21-years-old patient who was diagnosed at the age of eight years with common variable immunodeficiency (CVI) with gastrointestinal manifestations. In 2002 the patient was diagnosed with ulcerative jejunitis and after receiving different first-line treatments (mesalazine and corticosteroid) was not able to obtain a good control of the disease. Thus, his doctor decided to start treatment with azathioprine. Given the risk of severe immunosuppression derived from the CVI and the use of azathioprine the decision was taken to make a genetic polymorphism analysis of TPMT (rs2842934, rs2842934, rs1800460, rs1800584 and rs1142345) and NUDT15 (rs116855232, rs147390019, rs554405994 and rs186364861). DNAg was carried out using the Ramos et al. (2015) method and the characterisation was implemented using PCR and DNA sequencing. Results The patient showed a wild-type genetic profile for the polymorphism analysed. Consequently, he was prescribed with azathioprine with a complete dosage of 100 mg per day (2 mg/kg/d). After 3 months of treatment the patient had maintained a neutrophil normal range (higher than 2000 neutrophils per mm3) and, in addition, achieved a good control of the illness. Therefore the patient continued with the azathioprine at the usual dosage. Conclusion The integration of pharmacy services in the multidisciplinary teams is facilitating the implementation of pharmacogenetics in daily clinical practice in our hospitals. This kind of determinations provides the prescription clinicians with tools to improve the effectiveness and safety of treatments. In this case we have given an example in which the determination of a genetic WT profile for TPMT and NUDT15 has allowed for the full use of azathioprine dosage from the beginning of the treatment, which therefore resulted in an adequate control of the disease. No conflict of interest

5PSQ-081 Determination of genetic polymorphisms in tpmt and nudt-15 in the paediatric onco-haematologic patient. preliminary results

Background Genetic-polymorphisms in thiopurine-methyltransferase (TPMT) and Nudix-hydrolase15 (NUDT15) have been related to higher risk of toxicity associated with administration of 6-mercaptopurine(6-MP). Purpose To describe the implementation of polymorphisms determination in TPMT and NUDT15 in paediatric patients by a simple and economic method. Material and methods A multi-centre, prospective, observational study with a expected duration of 32 months was carried out. Participants were patients younger than 18 years who received treatment with 6-MP. Single nucleotide polymorphisms (SNPs) analysed were: TPMT (rs1800462;rs1800462; rs1800460;rs1142345 and rs1800584) and NUDT15 (rs116855232;rs147390019;rs554405994 and rs186364861). DNAg extraction was carried out using the Ramos et al. method and genotyping was done using PCR and subsequent DNA sequencing. The study was approved by the hospital’s Ethical Committee (CEIC). Legal guardians were requested to sign an informed consent form prior to inclusion. Results During the first 8 months, nine patients were included, with an average age of 3.5 (1–18)and 62.5% of them were females. Six of the included patients (66.6%) were diagnosed with acute lymphoblastic leukaemia, two with non-Hodgkin’s lymphoma (22.2%) and one with acute myeloid leukaemia. Eighty-one genetic-determinations were carried out. None of the patients presented a high-risk genotype for the TPMT gene. One of the children showed a medium-risk genotype *1/*3B,*1/*3C, but after 3 months of treatment with 6-MP he has not shown toxicity. This patient also showed a wild-type genotype for the NUDT15 gene which could explain the absence of toxicity during the treatment. Another patient has shown a heterozygous genotype for the rs116855232 and rs554405994 (NUDT15 gene). This patient has not already received treatment with 6-MP so we cannot evaluate the mutation influence yet. Conclusion Althought we have not found patients with high-risk polymorphisms in TPMT yet, we support the implementation of this screening because the presence of this genotypes is related to severe toxicity and even death-risk in these patients. We also have completed the procedure with the determination of mutations in the NUDT15 gene, increasing the probability of identifying patients with low tolerance to 6-MP. To our knowledge, the present study is the first to evaluate the effect of polymorphisms in both TPMT and NUDT15 in the treatment with 6-MP, so definitive results could cidentify how those polymorphisms affect the toxicity related to 6-MP. References and/or Acknowledgements 1. Ramos-Díaz. 2015May;75(5):1095–8. 2. Kotur, et al. 2015;16(15):1701–12. No conflict of interest

4CPS-146 Ustekinumab and adalimumab for psoriasis patients who are no-responders to etanercept: a comparative effectiveness study

Background Adalimumab and ustekinumab have demonstrated high effectiveness in the treatment of moderate-severe psoriasis in randomised controlled trials. There is, however, limited data available on the comparative effectiveness of ustekinumab and adalimumab in psoriasis patients unsuccessfully treated with a first biologic line with etanercept. Purpose To evaluate the comparative effectiveness of adalimumab and ustekinumab in patients previously treated with etanercept using PASI 90 score. Material and methods A single-centre, retrospective, observational, comparative study was carried out from 1 November 2011 to 31 November 2015. Participants were patients with moderate-severe psoriasis that, after unsuccessful etanercept therapy, were treated with adalimumab or ustekinumab. An unblinded revision of each patient’s clinical history was carried out to assess clinical data. The primary analysis compared the percentages of patients in each treatment group who achieved ≥90% improvement from baseline PASI score (PASI 90) at week 12. Secondary endpoints included percentages of patients with PASI 90 at week 96. Statistical analysis was performed with the SPSS 22.0 software. Results Thirty-four psoriasis patients were included in the study: 15 (44.1%) patients received adalimumab and 19 (55.9%) received ustekinumab as a second-line therapy. The median age in adalimumab and ustekinumab group were 58 (SD 6.7) and 50 years (SD 17.3) (p=0.08). After 12 weeks of study treatment, 68.4% of ustekinumab-treated patients (13/19) achieved a PASI 90 response against 46.6% (7/15) in the adalimumab group (p=0.2). At week 96, more patients had a PASI 90 in the ustekinumab group compared with the adalimumab group, but the difference was not statistically significant (68.4% versus 46.6%; p=0,2). Conclusion Previously studies have shown that adalimumab and ustekinumab are effective after anti-TNF inhibitors’ therapy. However, to our knowledge, the present study is the first to evaluate the comparative effectiveness measured as PASI 90 of ustekinumab and adalimumab in psoriasis patients that failed with etanercetp. Our results suggests that there is no significant difference in the efficacy of ustekinumab between ustekinumab and adalidumab in the percentage of patients achieving PASI90. Of course, these results need to be evaluated with randomised and prospective clinical trials. References and/or Acknowledgements 1. J Dermatolog Treat2015;26(3):217–22. 2. J Eur Acad Dermatol Venereol2011;25(9):1037–40. 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.

CP-225 UGT1A1*28 polymorphism and irinotecan effectiveness

Background UGT1A*28 polymorphisms have been associated with an increase in SN-38, the active metabolite of irinotecan. Thus some authors also related the presence of this mutated allele with an increase in the effectiveness of irinotecan treatment. Purpose To evaluate the influence of the UGT1A1*28 polymorphism on the effectiveness of irinotecan. Material and methods This was a prospective, observational, 4 year single centre study (November 2012–May 2016). All adult colorectal cancer patients treated with the FOLFIRI protocol (irinotecan 180 mg/m2/fluorouracil 400 mg/m2/fluorouracil 2400 mg/m2/leucovorin 200–400 mg/m2) were included. Inclusion criteria were: ECOG 0–1, haemoglobin > 10 g/dL, leucocytes >3000/mm3 and platelets >100 000/mm3). Effectiveness was evaluated as progression free survival (PFS) and overall survival (OS). The rs8175347 UGT1A1 polymorphism was established by analysing the genomic DNA of a peripheral blood sample. Genetic characterisation was carried out using LightClycler 480 platform and specific allele HybProbe fluorescent probes. The study was approved by the hospital’s ethical committee (CEIC) and classified as EPA-SP by the Spanish Agency for Drugs and Health Products (AEMPS) with GNC-QUI-2013-01 code. Patients were requested to sign an informed consent form prior to inclusion. Results The study included 34 patients, average age 60 (27–81) years, of which 77.7% were men. 90.6% of patients were treated with anti-VEGFR or anti-VEGFA, and irinotecan was prescribed as secondline treatment. 44.4% of patients showed UGT1A1 wild-type (WT) alleles, while 41.2% and 14.7% had heterozygous and mutated homozygous alleles, respectively. After 4 years of follow-up, median PFS and OS were 7.0 and 23.0 months for patients with any mutated allele in the UGT1A1 gene, while for patients with the WT genotype, values were 8.0 (p=0.4590) and 15.0 (p=0.6128) months, respectively. Moreover, median PFS and OS were 4.0 (p=0.648) and 44.0 (p=0.1628) months for patients with the *28/*28 genotype and 7.0 (p=0.650) and 23.0 months (p=0.8354) for heterozygous patients. Conclusion Our results show that the rs8175347 polymorphism in UGT1A1 does not influence the effectiveness of irinotecan. Prospective randomised studies with a large number of patients are required to establish if this polymorphism influences the effectiveness of irinotecan therapy. 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-022 Safety profile of glatiramer acetate 40 mg

Background Glatiramer acetate (GA) is a firstline therapy approved for the treatment of relapsing remitting multiple sclerosis (RRMS). GA 20 mg/mL (GA20) administered once daily by subcutaneous injection has been used since 2009. In 2014, modified treatment regimens–alternative dosages and low frequency administration schedules were introduced—GA 40 mg/mL (GA40) three times weekly. Purpose To analyse injection related adverse events (IRAEs) reported for GA20 and GA40 in our clinical practice. Material and methods This was a retrospective observational study of patients diagnosed with RRMS, receiving treatment with GA for at least for 6 months (January—June 2016). We studied all patients who started on GA40 three times weekly, as well as those converting from GA20 once daily to GA40, including naive and further lines of treatment. We excluded patients who wanted to get pregnant. The IRAEs analysed according to the System Organ Class were general disorders and administration site conditions, including local injection site reactions (ISRs), and symptoms or events related to immediate post-injection reactions (IPIRs). Results 52 patients were included: 23 patients (14 women, 9 men; mean age 43 years) were receiving treatment with GA40, 15 (7 women, 8 men) had converted from GA 20 and 10 patients were naive for GA. Five moderate/severe IRAEs related to ISRs and IPIRs were reported (21.7%), 2 of which were in patients who had converted from GA20. 29 patients (19 women, 10 men; mean age 46 years) were receiving treatment with GA20 for at least 6 months. One moderate IRAE associated with IPIR (3.4%) was reported in this group. Conclusion To our knowledge, post hoc analyses showed that patients receiving GA40 demonstrated a 60% reduction in the annualised event rate of moderate/severe IRAEs compared with GA20. In our study, from the total number of ISRs and IPIRs reported, GA40 had a significantly increased rate compared with GA20 (p<0.04). These outcomes suggest that moderate or severe reactions related to general disorders and administration site conditions were less frequent in GA20 treated patients. Due to the size of group, these results should be interpreted with caution; future analysis in clinical practice is necessary. References and/or acknowledgements Wolinsky JS, et al. Mult Scler Relat Disord2015;4:370–6. Available at http://dx.doi.org/10.1016/j.msard.2015.06.005 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.