Lipid profile changes associated with antiretroviral therapies in a real-world cohort. / [Artículo traducido] Cambios en el perfil lipídico asociados con las terapias antirretrovirales en una cohorte de vida real.

OBJECTIVE: To compare lipid profile changes and cardiovascular events among HIV naïve and experienced patients from a real-world cohort treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. METHOD: A retrospective cohort study in HIV naïve and experienced people at a reference hospital in Spain was done. During the follow-up (March 2015-June 2019), patients were treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. Epidemiological, clinical and immunovirological variables were recorded. A statistical analysis of the lipid profile at baseline, 48 and 120 weeks after initiating the study therapy, cardiovascular events (myocardial infarction, heart failure, cerebrovascular accident, deep venous thrombosis, myocardiopathy, non-ST- segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction) and cardiovascular risks factors was performed. Data were analysed in naïve and experienced patients from each of the study treatments. The data was obtained from the medical history. The statistical analysis was performed with SPSS v.24 software. RESULTS: A total of 266 and 191 patients receiving treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine were included in the study, respectively. After 120 weeks of treatment, a worsening of the lipid profile was found in the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group, both in naïve and experienced patients, whereas not so conspicuously observed in the dolutegravir/abacavir/lamivudine group. Statistically significant differences between both groups were found in experienced patients favoring dolutegravir/abacavir/lamivudine; in total cholesterol (204.1 ± 38.2 vs. 187.3 ± 29.4, p < 0.001) and LDL-C (126.1 ± 31.9 vs. 113.5 ± 28.5, p = 0.001) at week 48, and in total cholesterol (201.1 ± 33.4 vs. 188.7 ± 33.9, p = 0.013) and HDL-C (54.2 ± 15.6 vs. 48.3 ± 14.3, p = 0.01) at week 120. No significant differences in cardiovascular events were found, neither in naïve nor in experienced patients. CONCLUSIONS: The lipid profile among elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group worsened throughout the follow-up, both in naïve and experienced patients, not so remarkable in the dolutegravir/abacavir/lamivudine group. Both regimens were well tolerated, with similar rates of cardiovascular events.

Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Lipid profile changes associated with antiretroviral therapies in a real-world cohort.

OBJECTIVE: To compare lipid profile changes and cardiovascular events among HIV naïve and experienced patients from a real-world cohort treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. METHOD: A retrospective cohort study in HIV naïve and experienced people at a reference hospital in Spain was done. During the follow-up (March 2015-June 2019), patients were treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. Epidemiological, clinical, and immunovirological variables were recorded. A statistical analysis of the lipid profile at baseline, 48, and 120 weeks after initiating the study therapy, cardiovascular events (myocardial infarction, heart failure, cerebrovascular accident, deep venous thrombosis, myocardiopathy, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction), and cardiovascular risks factors was performed. Data were analysed in naïve and experienced patients from each of the study treatments. The data were obtained from the medical history. The statistical analysis was performed with SPSS v. 24 software. RESULTS: A total of 266 and 191 patients receiving treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine were included in the study, respectively. After 120 weeks of treatment, a worsening of the lipid profile was found in the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group, both in naïve and experienced patients, whereas not so conspicuously observed in the dolutegravir/abacavir/lamivudine group. Statistically significant differences between both groups were found in experienced patients favouring dolutegravir/abacavir/lamivudine; in total cholesterol (204.1±38.2 vs. 187.3±29.4, P < .001) and LDL-C (126.1±31.9 vs. 113.5±28.5, P = .001) at week 48, and in total cholesterol (201.1±33.4 vs. 188.7±33.9, P = .013) and HDL-C (54.2±15.6 vs. 48.3±14.3, P = .01) at week 120. No significant differences in cardiovascular events were found, neither in naïve nor in experienced patients. CONCLUSIONS: The lipid profile among elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group worsened throughout the follow-up, both in naïve and experienced patients, not so remarkable in the dolutegravir/abacavir/lamivudine group. Both regimens were well tolerated, with similar rates of cardiovascular events.

Renal profile of patients treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine: 120-week results from a real-world cohort.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) and dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) are currently available for HIV patients. OBJECTIVES: This study evaluated modifications in the renal safety profile in a large real-world cohort of patients who had received EVG/c/FTC/TAF or DTG/ABC/3TC. METHODS: A retrospective observational study of HIV-infected patients who received EVG/c/FTC/TAF or DTG/ABC/3TC between March 2015 and June 2019 at a reference hospital in north-western Spain was conducted. Epidemiological, clinical, immunovirological data and information regarding antiretroviral therapy were recorded. The statistical differences between treatments were calculated. RESULTS: A total of 457 patients were evaluated, 266 using EVG/c/FTC/TAF and 191 using DTG/ABC/3TC. Up to week 120, serum creatinine improved in both study groups among experienced patients (EVG/c/FTC/TAF 1.01±0.24 vs 0.91±0.19, p<0.001; DTG/ABC/3TC 1.08±0.24 vs 1.02±0.31, p<0.001), while in naïve patients serum creatinine remained stable compared with baseline. Statistically significant differences were found in serum creatinine when comparing both treatments at week 48 in experienced (0.94±0.21 vs 1.09±0.28, p<0.001) and naïve patients (0.89±0.16 vs 1.06±0.20, p=0.001), and among experienced patients at week 120 (0.91±0.19 vs 1.02±0.31, p=0.015) for the EVG/c/FTC/TAF and DTG/ABC/3TC groups, respectively. During the follow-up, 39 patients in EVG/c/FTC/TAF and 33 in DTG/ABC/3TC (p=0.449) discontinued treatment. The main reason for stopping treatment was adverse events, which were similar in both groups. CONCLUSIONS: During the follow-up, patients experienced changes that were not clinically relevant in both treatment groups. Differences in renal events were not found.

Treatment of high-risk bleeding with susoctocog alfa in a patient with acquired haemophilia A and a nosocomial severe acute respiratory syndrome coronavirus 2 infection.

We report the case of a man in his early 70s with idiopathic acquired haemophilia A and persistent high-titre type II inhibitors on immunosuppressive treatment to eradicate the inhibitor. As complications, he had a nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused severe pneumonia and an explosive inflammatory reaction that required tocilizumab and remdesivir treatment, and a high-risk retroperitoneal haematoma. Recombinant porcine factor VIII, susoctocog alfa, was requested from the Pharmacy Service in view of the extreme risk of thromboembolism resulting from the concomitant inflammatory storm caused by SARS-CoV-2. Improvement in the SARS-CoV-2 infection made it possible to complete the immunosuppressive treatment with rituximab. The patient was discharged with mycophenolate mofetil as immunosuppressive treatment after 89 days in hospital and 22 days of treatment with susoctocog alfa. His SARS-CoV-2 infection resolved and the haematoma evolved favourably.

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis.

Introduction: There is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting. Methods: Observational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI > 3). Mann-Whitney U test and Spearman's rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value < 0.05 was considered statistically significant. Results: A total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 µg/mL (range <0.1-1.8) vs. 0.4 µg/mL (range <0.1-0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 µg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders. Conclusion: A positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.

Evaluation of a Telemedicine pharmaceutical care program for coordination patient's transfer between hospital and primary care, using Telepharmacy.

OBJECTIVE: To report our experience with Telemedicine projects: a Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program and a Hospital Pharmacy/Primary Care Pharmacy  Electronic Cross-consultation Program. Results are reported in terms of  medication adherence, perceived quality and satisfaction, and economic  impact. METHOD: A) Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program: Phases of development: 1) Creation of a  work group; 2) definition of patient inclusion criteria; 3) selection of medicines; 4) integration of hospital and primary care pharmaceutical care; 5)  setting up of facilities in primary care; 6) logistics design; 7) creation of the Telemedicine system; 8) provision of training to primary care pharmacists; 9) establishment of a pharmaceutical care protocol; 10) obtaining patient informed consent. Medication adherence was evaluated using  dispensing records. Results were assessed based on a quality questionnaire.  Pharmacist evaluation was performed using a satisfaction questionnaire. The economic impact of the programs was assessed from patient's perspective from the estimated 1-year avoided direct costs of traveling from home to the  hospital. B) Webbased cross-consultation system: mining was performed of  web data from August 2018-June 2019. Analyzed items: hospital pharmacoterapeutic area, reasons, and results of consultation in primary and  hospital care. RESULTS: A) Telepharmacy Hospital Pharmacy / Primary Care Pharmacy Coordination Program: sample: 51 patients, 58% male. Mean  age  62.8 ± 18.0 years. 83.0% were pensioners; 69% were involved in an enteral  nutrition program. Baseline and post-intervention medication adherence, 95.82  ± 8.03 vs 85.23 ± 23.02 (p = 0.007). Patients  took 3.3 ± 1.4 hours to travel to the hospital; all patients assumed traveling costs. Average avoided cost per patient per year, €76.08 ± 38.77.  Average score on the satisfaction questionnaire, 9.4 ± 1.3 over 10. The most valued items were work/family reconciliation and cost savings. No items were identified as negative in the program. Pharmacist satisfaction was 9.0 ± 1.2 over 10. B) Electronic cross-consultation program: 458  consultations, 190 from secondary to primary care, and 268 from primary to secondary care. CONCLUSIONS: The Telemedicine programs enabled coordination of drug therapy monitoring between the hospital and the primary care pharmacy. Patients and professionals reported a high level of satisfaction with  the Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program, which had a very positive economic impact. Finally, the  two Telepharmacy programs integrate humanization strategies.

OBJETIVO: Analizar estrategias de Telemedicina y colaboración entre atención  primaria y atención hospitalaria: programa de Telefarmacia de Coordinación  entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria y  la plataforma e-interconsulta. Describir la implantación del programa  Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia  Hospitalaria y Atención Primaria y evaluar los resultados sobre adherencia  terapéutica, calidad percibida y satisfacción y económicos, así como las e- interconsultas realizadas entre atención hospitalaria y atención primaria.Método: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de  Farmacia Hospitalaria y Atención Primaria: fases de implantación: 1) creación  del grupo de trabajo; 2) establecimiento de criterios de inclusión de pacientes;  3) selección de medicamentos; 4) integración de la documentación de la  atención farmacéutica; 5) acondicionamiento hospide la consulta de atención  primaria; 6) diseño logístico; 7) creación del sistema de Telemedicina; 8)  formación a farmacéuticos de atención primaria; 9) protocolización de la  atención farmacéutica; 10) información al paciente y consentimiento  informado. La adherencia se evaluó por registro de dispensaciones. Evaluación  de los resultados mediante cuestionario de calidad percibida. Evaluación por  farmacéuticos mediante encuesta de satisfacción. Análisis del impacto  económico según costes directos estimados de los desplazamientos evitados  desde el domicilio hasta el hospital durante un año. B) Plataforma e- interconsulta: explotación de los datos de la plataforma web de agosto de  2018 a junio de 2019. Se analizó: área farmacoterapéutica en atención  hospitalaria, motivos y resultados de las mismas en atención primaria y  atención hospitalaria. RESULTADOS: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria: 51 pacientes incluidos, 58% varones. 62,8 ± 18,0 años de media de edad. 83,0% pensionistas; 69% adscritos al programa de nutrición enteral  domiciliaria. Adherencia previa y tras la implantación del programa: 95,82 ±  8,03 versus 85,23 ± 23,02 (p = 0,007). Los pacientes emplearon una media de 3,3 ± 1,4 horas en el desplazamiento al servicio de farmacia del hospital; el 100% asumió el gasto de los desplazamientos. Coste medio evitado por paciente/año: 76,08 ± 38,77 €. Media de valoración de la encuesta de satisfacción: 9,4 ± 1,3 sobre 10. Resultado de la encuesta de  satisfacción a farmacéuticos: 9,0 ± 1,2. B) Plataforma e-interconsulta: 458  consultas realizadas: 190 desde atención hospitalaria a atención primaria, y  268 desde atención primaria a atención hospitalaria. CONCLUSIONES: Estos programas de Telemedicina permiten un seguimiento farmacoterapéutico coordinado del paciente externo entre  farmacia hospitalaria y atención primaria. El programa Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y  Atención Primaria cuenta con una alta valoración de calidad percibida por  pacientes y farmacéuticos y un elevado impacto económico para el paciente.  Ambos proyectos integran estrategias de humanización que facilitan  proporcionar una atención farmacéutica más cercana al paciente, evitándole  desplazamientos innecesarios al hospital.

Pharmacokinetic and clinical monitoring through posologic changes in adalimumab intensification regimen from 40 mg every week to 80 mg every other week

Background: adalimumab dose escalation is often recommended for inflammatory bowel disease (IBD) patients incases of loss of response (LOR). The usual adalimumabintensification regimen was 40 mg every week. Recently,the pharmaceutical companies commercialized the 80 mginjection pen. In the biosimilars era, this pen was sold atthe same price as the 40 mg pen. Due to this and for patientcomfort, we proposed that our stable intensified adalimumab patients on a 40 mg every-week (ew) regimen change toa dose of 80 mg every-other-week (eow).Aim and methods: an observational study was performedto monitor outcome through this posologic change. Clinical,analytic parameters and adalimumab trough levels wereprospectively obtained at baseline, four and 12 monthsafter posologic change. The evolution of this cohort andcalculates savings were described.Results: thirteen patients were included in the study and themedian time of adalimumab intensification prior to posologic change to 80 mg eow was 32 months (IQR 29-63). Atfour months, all patients maintained adalimumab 80 mgeow. After month 4, two patients returned to the previousregimen after mild worsening, without significant changes in C-reactive protein (CRP), calprotectin or adalimumab-trough-levels. At one year, adalimumab was stoppedin one patient in remission with undetectable levels andpositive adalimumab-antibodies. No significant differencesin adalimumab-trough-levels were noted before and afterthe posologic change. Costs fell from 16,276 €/patient/yearof treatment to 8,812.15 €/patient/year of treatment.Conclusion: in IBD patients with stable response to adalimumab intensification regimen of 40 mg ew, changingto 80 mg eow seems to maintain response and similaradalimumab-trough-levels. Furthermore, it is cost-saving,although some patients may perceive mild symptoms. (AU)

Evaluación de un programa de atención farmacéutica en Telemedicina para la coordinación de la transición del paciente, entre atención hospitalaria – primaria, mediante Telefarmacia / Evaluation of a Telemedicine pharmaceutical care program for coordination patient’s transfer between hospital and primary care, using Telepharmacy

Objetivo: Analizar estrategias de Telemedicina y colaboración entreatención primaria y atención hospitalaria: programa de Telefarmacia deCoordinación entre los Equipos Asistenciales de Farmacia Hospitalariay Atención Primaria y la plataforma e-interconsulta. Describir la implantación del programa Telefarmacia de Coordinación entre los EquiposAsistenciales de Farmacia Hospitalaria y Atención Primaria y evaluar losresultados sobre adherencia terapéutica, calidad percibida y satisfaccióny económicos, así como las e-interconsultas realizadas entre atenciónhospitalaria y atención primaria.Método: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria: fases de implantación: 1) creación del grupo de trabajo; 2) establecimiento de criteriosde inclusión de pacientes; 3) selección de medicamentos; 4) integración dela documentación de la atención farmacéutica; 5) acondicionamiento. de la consulta de atención primaria; 6) diseño logístico; 7) creación delsistema de Telemedicina; 8) formación a farmacéuticos de atención primaria; 9) protocolización de la atención farmacéutica; 10) información alpaciente y consentimiento informado. La adherencia se evaluó por registro de dispensaciones. Evaluación de los resultados mediante cuestionariode calidad percibida. Evaluación por farmacéuticos mediante encuestade satisfacción. Análisis del impacto económico según costes directosestimados de los desplazamientos evitados desde el domicilio hasta elhospital durante un año. B) Plataforma e-interconsulta: explotación delos datos de la plataforma web de agosto de 2018 a junio de 2019. (AU)

Objective: To report our experience with Telemedicine projects: aTelepharmacy Hospital Pharmacy/Primary Care Pharmacy CoordinationProgram and a Hospital Pharmacy/Primary Care Pharmacy ElectronicCross-consultation Program. Results are reported in terms of medicationadherence, perceived quality and satisfaction, and economic impact.Method: A) Telepharmacy Hospital Pharmacy/Primary Care PharmacyCoordination Program: Phases of development: 1) Creation of a workgroup; 2) definition of patient inclusion criteria; 3) selection of medicines;4) integration of hospital and primary care pharmaceutical care; 5) setting up of facilities in primary care; 6) logistics design; 7) creation of theTelemedicine system; 8) provision of training to primary care pharmacists;9) establishment of a pharmaceutical care protocol; 10) obtaining patientinformed consent. Medication adherence was evaluated using dispensingrecords. Results were assessed based on a quality questionnaire. Pharmacist evaluation was performed using a satisfaction questionnaire. Theeconomic impact of the programs was assessed from patient’s perspectivefrom the estimated 1-year avoided direct costs of traveling from home tothe hospital. B) Webbased cross-consultation system: mining was performed of web data from August 2018-June 2019. Analyzed items: hospitalpharmacoterapeutic area, reasons, and results of consultation in primaryand hospital care.Results: A) Telepharmacy Hospital Pharmacy / Primary Care Pharmacy Coordination Program: sample: 51 patients, 58% male. Meanage 62.8 ± 18.0 years. 83.0% were pensioners; 69% were involved inan enteral nutrition program. Baseline and post-intervention medicationadherence, 95.82 ± 8.03 vs 85.23 ± 23.02 (p = 0.007). Patients took3.3 ± 1.4 hours to travel to the hospital; all patients assumed travelingcosts. Average avoided cost per patient per year, €76.08 ± 38.77. Average score on the satisfaction questionnaire, 9.4 ± 1.3 over 10. (AU)

Pharmacokinetic and clinical monitoring through posologic changes in adalimumab intensification regimen from 40 mg every week to 80 mg every other week.

BACKGROUND: Adalimumab dose escalation is often recommended for inflammatory bowel disease patients in cases of loss of response. The usual adalimumab intensification regimen was 40 mg every week. Recently the pharmaceutical companies commercialized the 80mg injection pen. In the biosimilars era, this pen was sold at the same price as the 40mg pen. Due to this and for patient comfort, we proposed that our stable intensified adalimumab patients on a 40mg every-week regimen, change to a dose of 80mg every-other-week. AIM AND METHODS: an observational study was performed to monitor outcome through this posologic change. Clinical, analytic parameters and adalimumab trough levels were prospectively obtained at baseline, 4 and 12 months after posologic change. The evolution of this cohort and calculates savings were described. RESULTS: 13 patients were included in the study and the median time of adalimumab intensification prior to posologic change to 80mg eow was 32 months (IQR 29-63). At 4 months, all patients maintained adalimumab 80mg every-other-week. After month 4, two patients returned to the previous regimen after mild worsening, without significant changes in CRP, calprotectin or adalimumab-trough-levels. At 1 year, adalimumab was stopped in one patient in remission with undetectable levels and positive adalimumab-antibodies. No significant differences in adalimumab-trough-levels were noted before and after the posologic change. Costs fell from 16276 €/patient/year of treatment to 8812.15 €/patient/year of treatment. CONCLUSION: In IBD patients with stable response to adalimumab intensification regimen of 40 mg every-week, changing to 80mg every-other-week seems to maintain response and similar adalimumab-trough-levels. Furthermore, it is cost-saving, although some patients may perceive mild symptoms.

Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10 Years Ago.

INTRODUCTION: The aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting. METHODS: This was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study. RESULTS: A total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1-8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6-175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival. CONCLUSIONS: This study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago.

Discontinuation due to neuropsychiatric adverse events with efavirenz- and dolutegravir-based antiretroviral therapy: a comparative real-life study.

OBJECTIVES: Despite the high efficacy of antiretroviral treatment, no drug is free from adverse events (AEs). Efavirenz (EFV) and dolutegravir (DTG) are antiretroviral drugs for which neuropsychiatric adverse events (NPAEs) have been described. This study evaluated the safety and tolerability of DTG-based and EFV-based antiretroviral regimens in HIV-infected patients. METHODS: A retrospective observational study was carried out in HIV-infected patients who started DTG- or EFV-based antiretroviral treatment from January 2008 to December 2018 at a reference hospital in north-western Spain. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. RESULTS: A total of 282 DTG- and 148 EFV-based therapies were initiated. During follow-up, statistically significant differences have been found between the rate of patients who discontinued DTG and EFV due to AEs (12.1% vs 35.8%, p<0.001) and the main AEs in both groups, NPAEs (8.2% vs 25.0%, p<0.001). Female gender (OR 2.610 (95% CI 1.327 to 5.133), p=0.005) was associated with discontinuations due to AEs. Patients with documented psychiatric disorders were at higher risk of discontinuation due to NPAEs (OR 4.782 (95% CI 1.190 to 19.220), p=0.027). The multivariate analysis showed a 61.2% risk reduction in benzodiazepine prescriptions in patients treated with DTG. In both groups, patients needed consultation and follow-up in the psychiatry unit (16.9% in the EFV group and 8.9% in the DTG group, p=0.021). CONCLUSIONS: We found a high rate of discontinuations due to AEs and NPAEs, prescription of benzodiazepines and a requirement for consultation in a psychiatric unit in both treatment groups, especially with EFV.

Desarrollo del simulador conversacional o chatbot Antidotos_bot para el manejo de intoxicaciones / Development of the @Antidotos_bot chatbot tool for poisoning management

Objetivo: Describir el desarrollo del simulador conversacional Antidotos_bot, para facilitar la búsqueda de información en la Guía de Administración de Antídotos y realizar cálculos útiles en el uso de antídotos.Método: En enero de 2019 planteamos el desarrollo de un simuladorconversacional de libre acceso en Telegram®, empleando la plataformaXenioo®. En el desarrollo del software se definió la forma de interaccióncon el usuario y se incorporaron funcionalidades de cálculo. Se realizóuna validación interna y en junio de 2019 se presentó Antidotos_bot.Resultados: Antidotos_bot incorporó información en castellano sobre49 antídotos en 57 intoxicaciones, permitiendo realizar tres tipos decálculos y consultar dos algoritmos de tratamiento. La consulta fue posible mediante 332 preguntas. La validación interna precisó cinco entrenamientos diferentes durante 2 meses. En julio 2020, Antidotos_bot tenía415 usuarios y los antídotos más consultados fueron glucagón, penicilinaG, protamina, n-acetilcisteína y flumazenilo. Mensualmente fueron realizados 29 cálculos, el número medio de nuevos usuarios fue de 3 y elnúmero medio de consultas por usuario fue de 3.Conclusiones: Antidotos_bot es una herramienta de apoyo en la tomade decisiones en intoxicaciones, que proporciona información actualizada de forma ágil, y podría contribuir a mejorar la calidad y seguridadasistencial en situaciones de emergencia. (AU)

Objective: To describe the development of the Antidotos_bot chatbottool, which is used to facilitate the search for information in the AntidoteAdministration Guide and to perform useful calculations in the use of antidotes.Method: In January 2019, we proposed developing a freely accessiblechatbot on Telegram® using Xenioo®. Software development defined theway it interacts with users and incorporated calculation functionalities.Internal validation was conducted and it was presented as Antidotos_botin June 2019.Results: Antidotos_bot included information in Spanish on 49 antidotes and 57 poisonings. Three types of calculations were provided andtwo treatment algorithms could be consulted. Consultation was possiblethrough 332 questions. Internal validation needed five sets of training over2 months. By July 2020, it had 415 users. The most frequently consultedantidotes were glucagon, penicillin G, protamine, n-acetylcysteine andflumazenyl. Regarding monthly activity, there was an average of 29 calculations and an average of three new users and three queries per user.Conclusions: Antidotos_bot is a poisoning management decisionmaking tool that provides up-to-date information in a user-friendly manner.It could contribute to improving the quality and safety of care in emergency situations. (AU)

Development of the @Antidotos_bot chatbot tool for poisoning management.

OBJECTIVE: To describe the development of the Antidotos_bot chatbot tool, which is used to facilitate the search for information in the Antidote Administration Guide and to perform useful calculations in the use of antidotes. METHOD: In January 2019, we proposed developing a freely accessible chatbot on Telegram® using Xenioo®. Software development  defined the way it interacts with users and incorporated calculation  functionalities. Internal validation was conducted and it was presented as  Antidotos_bot in June 2019. RESULTS: Antidotos_bot included information in Spanish on 49 antidotes and 57 poisonings. Three types of calculations were provided  and two treatment algorithms could be consulted. Consultation was  possible through 332 questions. Internal validation needed five sets of  training over 2 months. By July 2020, it had 415 users. The most  frequently consulted antidotes were glucagon, penicillin G, protamine, n- acetylcysteine and flumazenyl. Regarding monthly activity, there was an  average of 29 calculations and an average of three new users and three  queries per user. CONCLUSIONS: Antidotos_bot is a poisoning management decisionmaking tool that provides up-to-date information in a user-friendly manner. It could contribute to improving the quality and safety of care in  emergency situations.

Objetivo: Describir el desarrollo del simulador conversacional Antidotos_bot, para facilitar la búsqueda de información en la Guía de  administración de Antídotos y realizar cálculos útiles en el uso de  antídotos.Método: En enero de 2019 planteamos el desarrollo de un simulador conversacional de libre acceso en Telegram®, empleando la  plataforma Xenioo®. En el desarrollo del software se definió la forma de  interacción con el usuario y se incorporaron funcionalidades de cálculo. Se  realizó una validación interna y en junio de 2019 se presentó  Antidotos_bot.Resultados: Antidotos_bot incorporó información en castellano sobre 49  antídotos en 57 intoxicaciones, permitiendo realizar tres tipos de cálculos y consultar dos algoritmos de tratamiento. La consulta fue posible mediante  332 preguntas. La validación interna precisó cinco entrenamientos diferentes durante 2 meses. En julio 2020, Antidotos_bot  tenía 415 usuarios y los antídotos más consultados fueron glucagón,  penicilina G, protamina, n-acetilcisteína y flumazenilo. Mensualmente  fueron realizados 29 cálculos, el número medio de nuevos usuarios fue de  3 y el número medio de consultas por usuario fue de 3.Conclusiones: Antidotos_bot es una herramienta de apoyo en la toma de  decisiones en intoxicaciones, que proporciona información actualizada de  forma ágil, y podría contribuir a mejorar la calidad y seguridad asistencial  en situaciones de emergencia.

Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases.

WHAT IS KNOWN AND OBJECTIVE: Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions. METHODS: A systematic review of cases was carried out following the guidelines established by "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). The research was carried out using the PubMed-Medline and Embase databases, between July 1984 and March 2021. RESULTS AND DISCUSSION: A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5-88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end-stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2-28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2-180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days. WHAT IS NEW AND CONCLUSION: The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis.

e-Interconsultations between a hospital pharmacy service and primary care pharmacy units in Spain.

PURPOSE: To analyse the profile of consultations made using an electronic platform system (e-Interconsultation) of communication between the hospital pharmacy service and primary care pharmacy units. METHOD: Descriptive and retrospective analysis of the number and type of e-Interconsultations for 3 years in a health area. DATA SOURCE: data mining of the e-Interconsultation platform (Microsoft Sharepoint software). RESULTS: A total of 1152 interconsultations have been made and 90.6% (88.9%-92.4% 95% CI) solved. 477 (41.1%) of them were referrals from hospital care to primary care in addition to 675 (58.6%) from primary to hospital care. The validation of prescriptions and the need for drug monitoring in primary care are among the main reasons for consultation. CONCLUSION: This two-way electronic platform of communication is a good mechanism that collaborates in patients' transit between different healthcare levels because it allows us to facilitate, normalise and document consults, referrals and pharmaceutical interventions between hospital care and primary care. Therefore, it helps us provide better quality pharmaceutical care to our patients.

Results of the implementation of a pharmacogenomics platform based on NGS technologies. Combining clinical and research approaches.

OBJECTIVE: As more genes are incorporated into pharmacogenomic care  processes and more importance is given to rare variants, the use of targeted  capture sequencing panels has been proposed as a very efficient alternative  due to their affordability, high throughput, and deep coverage, all of them  characteristics of high-quality next-generation sequencing data. The purpose of  this study is to describe the prevalence of clinically actionable  pharmacogenetic variants previously described in the scientific literature, as  well as that of new variants identified by next-generation sequencing  technologies, and to evaluate the drugs potentially affected by such variants. METHOD: A panel of 18 clinically actionable pharmacogenomics-related genes  was evaluated in 41 subjects diagnosed with breast cancer undergoing  neoadjuvant treatment. The prevalence of previously descri- bed clinically  actionable variants as well as of phenotypes classified according to current  interpretation standards was studied. The pharmacological treatments  potentially affected by the identified variants were also evaluated. An  estimation was made of the prevalence of not previously described, possibly  deleterious, variants selected using bioinformatics criteria. RESULTS: All subjects carried clinically actionable variants, with a mean of 4.02  genes affected by each variant per individual. VKORC1, CYP4F2, CYP2C19,  CYP2D6 and CYP2B6 were the most polymorphic genes and were present with  actionable phenotypes in more than 50% of patients; 15-50% had actionable  phonotypes in UGT1A1, SLCO1B1, CYP2C9 and TPMT and 2-15% in HLA-B,  CYP3A5, HLA-A and DPYD. No actionable variants were identified in RYR1,  CACNA1S, G6PD, F5 and NUDT15. These variants had the potential to affect  response to 84% of the drugs described in the leading pharmacogenetic  guidelines. Possibly deleterious variants not previously described accounted for  11.4% of all clinically actionable variants and were present in 12.2% of  patients. CONCLUSIONS: The results obtained show a high prevalence of clinically actionable variants, both common, i.e., previously described in the  literature, and rare, i.e., not previously studied with conventional technological  approaches. The latter are candidates for a more exhaustive  molecular and/or clinical characterization.

OBJETIVO: A medida que se incorporan más genes a los procesos  farmacogenómicos asistenciales y se otorga más importancia a las variantes raras, el uso de paneles de secuenciación dirigida por captura se ha  propuesto como una alternativa muy eficiente atendiendo a sus costes, su  rendimiento y la cobertura profunda, característica de los datos de  secuenciación de nueva generación de alta calidad. El objeto de este trabajo es  describir la prevalencia de variantes farmacogenéticas clínicamente  procesables descritas previamente en la literatura científica, así como de  nuevas variantes identificadas mediante tecnologías de secuenciación de nueva  generación y evaluar los fármacos potencialmente afectados por estas  variantes.Método: Se evaluó un panel de 18 genes relacionados con la  farmacogenómica clínicamente procesables en 41 individuos con diagnóstico de  cáncer de mama que van a recibir tratamiento adyuvante y neoadyuvante.  Se estudió  la literatura científica, así como de los fenotipos farmacogenéticos  clasificados según los estándares de interpretación actuales. Asimismo, se  evaluaron los tratamientos farmacológicos potencialmente afectados por las  variantes identificadas. Se estimó la prevalencia de variantes posiblemente  deletéreas no descritas previamente seleccionadas con criterios  bioinformáticos. RESULTADOS: Todos los individuos fueron portadores de variantes clínicamente procesables, con una media de 4,02 genes afectados por alguna variante por individuo. Los genes VKORC1, CYP4F2, CYP2C19, CYP2D6 y CYP2B6 fueron los más polimórficos, con más de un 50% de  pacientes con fenotipos procesables; un 15-50% en UGT1A1, SLCO1B1,  CYP2C9 y TPMT y un 2-15% HLA-B, CYP3A5, HLA-A y DPYD. No se  identificaron variantes procesables en RYR1, CACNA1S, G6PD, F5 y NUDT15.  Estas variantes afectarían a la respuesta de un 84% de los fármacos descritos  en las principales guías de farmacogenética. Las variantes posiblemente  deletéreas no descritas previamente supusieron un 11,4% del total de  variantes clínicamente procesables y están presentes en un 12,2% de los  pacientes. CONCLUSIONES: Los resultados obtenidos constatan una alta prevalencia de  variantes clínicamente procesables tanto comunes, previamente descritas en la  literatura, como raras, no estudiadas con abordajes tecnológicos convencionales y candidatas a una caracterización molecular y/o  clínica más exhaustiva.

Influence of drug-drug interactions on effectiveness and safety of direct-acting antivirals against hepatitis C virus.

OBJECTIVES: Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug-drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug-drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients. METHODS: Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug-drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug-drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug-drug interactions related to the effectiveness of direct-acting antivirals. RESULTS: Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug-drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug-drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug-drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841). CONCLUSIONS: Drug-drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug-drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals.

Resultados de implementación de una plataforma farmacogenómica basada en tecnologías NGS. Combinación de abordajes asistencial y de investigación / Results of the implementation of a pharmacogenomics platform based on NGS technologies. Combining clinical and research approaches

Objetivo: A medida que se incorporan más genes a los procesos farmacogenómicos asistenciales y se otorga más importancia a las variantesraras, el uso de paneles de secuenciación dirigida por captura se ha propuesto como una alternativa muy eficiente atendiendo a sus costes, su rendimiento y la cobertura profunda, característica de los datos de secuenciaciónde nueva generación de alta calidad. El objeto de este trabajo es describirla prevalencia de variantes farmacogenéticas clínicamente procesables descritas previamente en la literatura científica, así como de nuevas variantesidentificadas mediante tecnologías de secuenciación de nueva generacióny evaluar los fármacos potencialmente afectados por estas variantes.Método: Se evaluó un panel de 18 genes relacionados con la farmacogenómica clínicamente procesables en 41 individuos con diagnóstico de cáncerde mama que van a recibir tratamiento adyuvante y neoadyuvante. Se estudió la prevalencia de variantes clínicamente procesables previamente descritas enla literatura científica, así como de los fenotipos farmacogenéticos clasificadossegún los estándares de interpretación actuales. Asimismo, se evaluaron lostratamientos farmacológicos potencialmente afectados por las variantes identificadas. Se estimó la prevalencia de variantes posiblemente deletéreas nodescritas previamente seleccionadas con criterios bioinformáticos. (AU)

Objective: As more genes are incorporated into pharmacogenomiccare processes and more importance is given to rare variants, the use oftargeted capture sequencing panels has been proposed as a very efficient alternative due to their affordability, high throughput, and deep coverage, all of them characteristics of high-quality next-generation sequencingdata. The purpose of this study is to describe the prevalence of clinicallyactionable pharmacogenetic variants previously described in the scientificliterature, as well as that of new variants identified by next-generationsequencing technologies, and to evaluate the drugs potentially affectedby such variants.Method: A panel of 18 clinically actionable pharmacogenomics-related genes was evaluated in 41 subjects diagnosed with breast cancerundergoing neoadjuvant treatment. The prevalence of previously described clinically actionable variants as well as of phenotypes classifiedaccording to current interpretation standards was studied. The pharmacological treatments potentially affected by the identified variants were alsoevaluated. An estimation was made of the prevalence of not previouslydescribed, possibly deleterious, variants selected using bioinformaticscriteria. (AU)

Fingolimod in multiple sclerosis: profile of use in habitual practice.

OBJECTIVES: Fingolimod is the first oral drug indicated in monotherapy as a modifier of the course of very active relapsing-remitting multiple sclerosis (RRMS). The safety profile of fingolimod is well established in clinical trials and post-marketing studies. Our objective was to study the profile of fingolimod use in our health area. METHODS: A retrospective, observational, descriptive study was performed on the use of fingolimod in adult patients diagnosed with RRMS between January 2015 and February 2017 or until suspension of treatment in a reference hospital in north-western Spain. RESULTS: A total of 55 patients were included with a mean±SD time of treatment with fingolimod of 26±14.6 months (range 2-53). Thirteen patients permanently discontinued the treatment (10 due to outbreaks/disease progression and 3 due to adverse effects). No statistically significant differences were found between the percentage of patients who discontinued fingolimod and who had received only one previous treatment and those who had received two or more treatments. No cases of symptomatic bradycardia were reported. CONCLUSIONS: Fingolimod is a safe treatment for patients with multiple sclerosis.