Effectiveness and safety of pembrolizumab monotherapy in patients with locally advanced or metastatic non-small-cell lung cancer.

INTRODUCTION: Immunotherapy has become a standard treatment for lung cancer; the objective of this study was to evaluate the effectiveness, safety of pembrolizumab monotherapy in patients with advanced or metastatic non-small-cell lung cancer used in real-world clinical practice. MATERIAL AND METHODS: Retrospective observational study of every patient treated with pembrolizumab in our centre from January 2017 to June 2019. Outcomes collected: sex, age, Eastern Cooperative Oncology Group, programmed death receptor 1 level, previous metastatic line therapies, adverse events and smoking status. RESULTS: A total of 62 patients were reviewed. The median age was 62.34 ± 10.62 years, 48 (77.41%) were men and 91.93% of patients had Eastern Cooperative Oncology Group 0. The median dose administered was 170.5 mg (108 - 240 mg) and the median follow-up was 3 months (range: 1 - 38). A median of four cycles of pembrolizumab (range: 1 - 56) were administered as monotherapy. The reason for treatment discontinuation was mainly due to disease progression in 38.70% of patients or death in 30.64%. As first-line pembrolizumab monotherapy, median progression-free survival was 7.7 months (95% CI: 3.66 - 11.73) (N = 33). With respect to patients who were treated in second-third-line treatment, median progression-free survival was 3.5 months (95% CI: 2.40 - 4.59) (N=29). As to overall survival, pembrolizumab-treated patients as first-line treatment reached 19 months median OG (95% CI: 13.36 - 24.63) (N = 33) and those treated in second-third-line treatment got 11 months (95% CI: 3.4 - 18.5). A total of 64.51% of patients presented some adverse events to pembrolizumab however, only, 9.38% of them were grade 3. CONCLUSION: Pembrolizumab represents an effective and feasible alternative in terms of progression-free survival. It is a well-tolerated treatment option.

Effectiveness of 12 week ledipasvir/sofosbuvir and predictors of treatment failure in patients with hepatitis C / Efectividad de ledipasvir/sofosbuvir durante 12 semanas de tratamiento y factores predictivos de fracaso del tratamiento en pacientes con hepatitis C

INTRODUCTION: The efficacy of ledipasvir/sofosbuvir (LDV/SOF) have been demonstrated in randomized controlled trials, however,there is an unmet need for real-world effectiveness data. It is important to gather data regarding potential predictors of treatment failure with (LDV/SOF). Predictors of sustained virologic response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. The objectives of this study were to evaluate the effectiveness of LDV/SOF, SVR12 as main endpoint and SVR24 as second endpoint, and identify predictors of treatment failure. MATERIAL AND METHODS: Retrospective and observational study carried out from April 2015 to January 2016. Inclusion criteria: patients with HCV infection treated with LDV/SOF for 12 weeks during study period. The patients that were treated during 24 weeks were excluded as well as those treated with peg-interferon. Binary logistic regression was used to predict what variable was associated with treatment failure. RESULTS: A total of 122 patients were analyzed achieving SVR12 91.80% (112/122) of them. The patients with HCV genotype (GT) 1a or GT1b or GT4 achieved SVR12. Only one pre-treated non-cirrhotic HCV GT1 patients relapsed to treatment. The lowest SVR12 were obtained for GT3, 43.75%, (7/16). Everybody that got SVR12 achieved SVR24. None of the variables analyzed significantly influenced the SVR12, except GT (p = 0.001). Almost all the relapses occurred in GT3. CONCLUSION: LDV/SOF combination has been very effective to treat GT1 and GT4 infected patients, however, has constituted a suboptimal therapeutic option for those patients infected with GT3, regardless of the rest of the variables analyzed

INTRODUCCIÓN: La eficacia de ledipasvir/sofosbuvir (LDV/SOF) se ha demostrado en ensayos clínicos, sin embargo, son necesarios más estudios sobre su eficacia en la práctica clínica. Además es importante estudiar los posibles factores predictivos de fracaso de tratamiento con LDV/SOF. Los factores predictivos de respuesta viral sostenida (RVS) a antivirales de acción directa pueden informar sobre decisiones de tratamiento. Los objetivos de este estudio fueron evaluar la efectividad de LDV/SOF, RVS12 como variable principal y RVS24 como secundaria, e identificar los factores predictivos de fracaso del tratamiento. MATERIAL Y MÉTODOS: Estudio retrospectivo y observacional realizado desde abril de 2015 a enero de 2016. Criterios de inclusión: pacientes con infección por VHC tratados con LDV/SOF durante 12 semanas. Se excluyeron los pacientes tratados durante 24 semanas y los tratados con peg-interferón. Aplicamos el método estadístico denominado regresión logística binaria para predecir qué variable estaba relacionada con el fracaso del tratamiento. RESULTADOS: Se analizaron 122 pacientes logrando el 91,80% (112/122) RVS12. Los pacientes infectados con genotipo (GT) 1a o GT1b o GT4 lograron RVS12. Solo un paciente, no cirrótico y previamente tratado, infectado con GT1 no alcanzó RVS12. Las tasas más bajas de RVS12 se obtuvieron para GT3, 43.75%, (7/16). Todos los pacientes que obtuvieron RVS12 lograron RVS24. Ninguna de las variables analizadas influyó significativamente en la RVS12, excepto GT (p = 0.001). Casi todas las recaídas ocurrieron en GT3. CONCLUSIONES: La combinación LDV/SOF ha sido muy efectiva para tratar a los pacientes infectados con GT1 y GT4, sin embargo, ha constituido una opción terapéutica subóptima para los infectados con GT3, independientemente del resto de las variables analizadas

Diagnóstico al alta y causas de mortalidad de pacientes VIH+ ingresados en un hospital de tercer nivel / Hospital admission and mortality causes of HIV patients in a third level hospital

INTRODUCCIÓN: El objetivo del presente trabajo es describir el perfil de los pacientes VIH que ingresan en un hospital de tercer nivel así como analizar las causas de ingreso hospitalario y de mortalidad durante el mismo. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo llevado a cabo en un Hospital de tercer nivel. Criterios de inclusión: Pacientes ≥18 años con prescripción de tratamiento antirretroviral (TAR) y diagnóstico de VIH conocido o descubierto durante el ingreso.como motivo de ingreso hospitalario se utilizó el diagnóstico al alta de cada paciente. Se recogieron variables clínicas, analíticas así como las causas de exitus. RESULTADOS: En el periodo de estudio ingresaron un total de 162 pacientes VIH. Cumplieron los criterios de inclusión 128, de los cuales 8 fueron diagnosticados como VIH de novo. Un 79,7% fueron varones; edad 50,29+/-9,81 años. El principal diagnóstico al alta (38,3%) fueron ciertas enfermedades infecciosas y parasitarias (Clasificación CIE-10) y dentro de esta clasificación, las infecciones directamente relacionadas con el VIH fueron las mayoritarias (24,1%). Las tasas de mortalidad de los pacientes VIH ≥18 años que ingresaron en el Hospital (años 2016 y 2017) fue del 13,52%. Las causas de muerte más frecuentes fueron ciertas enfermedades infecciosas y parasitarias seguidas de neoplasias. CONCLUSIONES: Nuestros resultados enfatizan la necesidad de seguir reforzando el diagnóstico precoz de VIH así como la profilaxis primaria de Pneumocysitis jirovecii en los pacientes VIH. Insistir en la adherencia al TAR desde las consultas de seguimiento de especialista en enfermedades infecciosas y en las consultas de atención farmacéutica, concienciar a los clínicos en la prescripción del TAR durante el ingreso hospitalario así como solicitar analíticas de CV y linfocitos CD4 a todos los pacientes VIH ingresados en el Hospital

INTRODUCTION: The aim of this study is to describe the HIV population admitted to a tertiary level hospital and analyze hospital admission and mortality causes during hospitalization. MATERIAL AND METHODS: Observational, retrospective study carried out in a third level Hospital. Inclusion criteria: Patients ≥18 years with a prescription of ART and diagnosis of HIV known or discovered during admission. It was accepted hospital ward discharge diagnose as hospitalization causes. Clinical, analytical outcomes as well as causes of mortality were collected. RESULTS: Among 162 hospitalized HIV infected, 128 met the inclusion criteria, 8 of those were diagnosed as naive HIV patients.79.7% were male; Age 50.29 +/- 9.81 years. The main reasons for hospital admissions (38.3%) were certain infectious and parasitic diseases (ICD-10 Classification) and more specifically human immunodeficiency virus [HIV] disease represented 24,1% of whole hospitalizations. Mortality rates of ≥18 years HIV patients that were admitted to hospital during 2016-2017 were the 13.52%. The main causes of death were certain infectious and parasitic diseases followed by malignancies. CONCLUSIONS: Our results emphasize the need of intensifying the HIV early diagnosis as well as Pneumocystis jirovecii primary prophylaxis. Insist on ART adherence from infectology follow-up appointment and pharmacy care consultations, educate clinics on ART treatment prescription during hospital admission as well as requesting viral and CD4 lymphocytes loads to every HIV admitted patients

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital / Tratamientos libres de interferon en pacientes con hepatitis C y genotipo 3 en un hospital terciario

Introduction. Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and allcause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis. Material and methods. Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24). Results. During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/ SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection. Conclusions. In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received (AU)

Introducción. El virus de la hepatitis C (VHC) genotipo 3 representa una entidad única dentro del tratamiento de la hepatitis C y múltiples estudios sugieren que la infección del VHC genotipo 3 está asociada a una progresión más rápida de la enfermedad comparado con otros genotipos, resultando en un mayor riesgo de cirrosis, carcinoma hepatocelular y mortalidad. En el presente estudio se evaluó la efectividad del tratamiento ledipasvir/sofosbuvir ± ribavirina (LDV/SOF ± RBV) y sofosbuvir + daclatasvir (SOF + DCV) durante 12 semanas en pacientes con VHC genotipo 3 naive o pre-tratados, con o sin cirrosis. Material y métodos. Se realizó un estudio observacional, retrospectivo en un hospital de tercer nivel. El periodo de estudio comprendió 9 meses (abril 2015-enero 2016). Criterios de inclusión: pacientes con hepatitis C y genotipo 3 que fueron tratados con LDV/SOF ± RBV o con SOF + DCV durante 12 semanas. Los pacientes que fueron tratados durante 24 semanas fueron excluidos así como aquellos que se trataron con peginteferon. La variable principal fue la respuesta viral sostenida (RVS) a semana 12 (RVS12) y la variable secundaria fue RVS24. Resultados. En el periodo de estudio se trataron en nuestro hospital 603 pacientes: 71 con genotipo 3. Se incluyeron en el análisis 46 pacientes, que fueron tratados con LDV/SOF ± RBV o SOF + DCV durante 12 semanas. El 43,75% (7/16) de todos los pacientes tratados con LDV/SOF alcanzaron RVS12, el 90% (9/10) de los pacientes tratados con LDV/SOF + RBV consiguieron RVS12 y el 95% (19/20) de los pacientes tratados con SOF + DCV. Se obtuvieron diferencias significativas (p=0,001) entre LDV/SOF y SOF + DCV y entre LDV/SOF + RBV y LDV/SOF (p=0,018). Conclusiones. En nuestra cohorte de pacientes, las combinaciones de SOF + DCV y LDV/SOF + RBV, administrados durante 12 semanas, fueron las más efectivas tanto en pacientes con cirrosis (RVS12 90% y 80%, respectivamente), como en pacientes sin cirrosis (RVS12 100% en ambos casos). Todos los pacientes que alcanzaron RVS12, también alcanzaron RVS24 independientemente del tratamiento recibido (AU)

Monoterapia con darunavir/cobicistat. Experiencia en un hospital de tercer nivel / Darunavir/cobicistat monotherapy. Experience in a tertiary hospital

Introducción. La monoterapia con inhibidores de la proteasa potenciados con ritonavir (IP/r): darunavir (DRV/r) o lopinavir (LPV/r), sólo está contemplada en las principales guías de tratamiento en pacientes pretratados para evitar toxicidad asociada a inhibidores de transcriptasa inversa análogos de nucleósidos/nucleótidos (ITIAN), reducir costes y simplificar el tratamiento antirretroviral (TAR). Para iniciar una monoterapia basada en IP/r según las guías GESIDA del año 2016, es necesario que el paciente cumpla los siguientes criterios: ausencia de hepatitis crónica B, carga viral plasmática (CVP) (<50 copias/ mL) durante al menos 6 meses y ausencia de mutaciones en el gen de la proteasa o fracasos virológicos (FV) previos a IP/r. Actualmente no hay estudios que evalúen la eficacia y seguridad de una monoterapia con darunavir/cobicistat (DRV/COBI). Material y Métodos. Se trata de un estudio prospectivo en el que se incluyeron pacientes VIH pretratados con DRV/r en monoterapia que cambiaron a una monoterapia con DRV/ COBI. El objetivo de nuestro estudio es describir la efectividad y seguridad de la monoterapia con DRV/COBI. Resultados. Se estudiaron 78 pacientes. Los pacientes tuvieron una mediana de 31,29 (6-74,82) meses de monoterapia con DRV/r previo al cambio a DRV/COBI en monoterapia. Nueve de los 78 pacientes desarrollaron 'blips' (CVP: 50-200 copias/ml) y cuatro pacientes tuvieron CVP≥ 200 copias/mL. Un 83,3% (65/78) se mantuvieron con CVP indetectable. En cuanto a la seguridad, no hubo diferencias importantes en el perfil lipídico, función hepática (transaminasas) y función renal entre DRV/r y DRV/COBI en monoterapia. Conclusiones. DRV/COBI en monoterapia, parece ser efectivo y seguro (perfil lipídico, hepático y renal). Sin embargo, deberían diseñarse estudios específicos que comparasen DRV/r vs. DRV/COBI en monoterapia para comprobar estos resultados (AU)

Introduction. Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r. Currently, there are no studies that evaluate the efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy. Methods. This prospective study analyzed pretreated HIV patients with DRV/r monotherapy that were switched to DRV/ COBI monotherapy. The aim of the study is to describe the effectiveness and safety of the DRV/COBI monotherapy. Results. Seventy-eight patients were evaluated. Patients had a median of 31.29 months of DRV/r monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed 'blips' (plasma viral load: 50-200 copies/ml) and four patients had plasma viral load ≥200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable plasma viral load. As for safety, there were no significant differences in lipid profile, liver function (transaminases) and renal function between DRV/r and DRV/COBI monotherapy. Conclusions. DRV/COBI monotherapy seems to be effective and safe (lipid profile, liver and kidney function). However, it would be necessary to design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these results (AU)

Biterapia como alternativa de tratamiento en los pacientes VIH pretratados: experiencia en un hospital de tercer nivel / Dual therapy as an alternative treatment in HIV pretreatred patients: experience in a tertiary hospital

INTRODUCCIÓN: La biterapia se plantea como una alternativa efectiva para prevenir la aparición de efectos secundarios y comorbilidades asociadas al tratamiento prolongado con antirretrovirales (ARV) y una forma de simplificación del tratamiento antirretroviral (TAR) para mejorar la adherencia en determinados pacientes, además de una posible opción de tratamiento en pacientes en los que hayan fracasado TAR previos. MÉTODOS: El objetivo del estudio es describir la efectividad, grado de adherencia y costes de los regímenes de biterapia utilizados en los pacientes VIH pretratados en un hospital de tercer nivel. RESULTADOS: Se estudiaron 38 pacientes (8 se excluyeron). Los principales motivos de cambio a biterapia fueron evitar los efectos adversos del TAR anterior (40%), la simplificación (36,67 %) y el rescate virológico (20%). Los esquemas de bi¬terapia más utilizados fueron: IP/r + INI (26,67%), IP/r + ITIAN (23,33%), IP/r + ITINN (23,33%), IP/r + CCR5 (16,66%) e INI + ITINN (10%). Los ARV más utilizados fueron: DRV/r + RAL en el 23,33 % de los pacientes; DRV/r + 3TC en el 20% y DRV/r + ETR en el 16,67 %. La adherencia antes del cambio a biterapia fue del 86,79% y tras el cambio a biterapia fue del 96,27%. El ahorro económico que supuso el cambio a biterapia de estos pacientes fue de 3.635,16 €. CONCLUSIÓN: La biterapia con IP/r se plantea como una alternativa eficiente comparada con la terapia convencional en pacientes pretratados

INTRODUCTION: Dual therapy regimen might be an effective alternative to prevent the occurrence of side effects and comorbidities associated with prolonged treatment with antiretroviral (ARV) and a way of simplification of antiretroviral therapy (ART) to improve adherence in certain patients. It also represents a potential treatment option for patients who have failed previous TAR. METHODS: The aim of the study is to describe the effectiveness, adherence and costs of dual therapy regimen used in pretreated HIV patients in tertiary hospital. RESULTS: Thirty-eight patients were studied (eight were excluded). Reasons for simplification to dual therapy were previous treatment toxicity (40%), simplification (36.67%) and virological rescue (20%). The dual therapy regimens most used were: IP/r + INSTIs (26.67%), IP/r + NRTIs (23.33%), IP/r + NNRTIs (23.33%), IP/r+ CCR5 (16.66%) e INSTIs + NNRTIs (10%). ARV more used were darunavir/ritonavir (DRV/r) + raltegravir (23.33 %); DRV/r + lamivudine (20%) y DRV/r + etravirine (16.67 %). Adherence was 86.79% before switching to dual therapy and 96.27% after switching. The cost savings of switching to dual therapy of these patients was € 3,635.16. DISCUSSION: Dual therapy with IP/r might be an effective alternative to selected treatment experienced patients compared with conventional therapy

[Dual therapy as an alternative treatment in HIV pretreated patients: experience in a tertiary hospital]. / Biterapia como alternativa de tratamiento en los pacientes VIH pretratados: experiencia en un hospital de tercer nivel.

OBJECTIVE: Dual therapy regimen might be an effective alternative to prevent the occurrence of side effects and comorbidities associated with prolonged treatment with antiretroviral (ARV) and a way of simplification of antiretroviral therapy (ART) to improve adherence in certain patients. It also represents a potential treatment option for patients who have failed previous TAR. METHODS: The aim of the study is to describe the effectiveness, adherence and costs of dual therapy regimen used in pretreated HIV patients in tertiary hospital. RESULTS: Thirty-eight patients were studied (eight were excluded). Reasons for simplification to dual therapy were previous treatment toxicity (40%), simplification (36.67%) and virological rescue (20%). The dual therapy regimens most used were: IP/r + INSTIs (26.67%), IP/r + NRTIs (23.33%), IP/r + NNR-TIs (23.33%), IP/r+ CCR5 (16.66%) e INSTIs + NNRTIs (10%). ARV more used were darunavir/ritonavir (DRV/r) + raltegravir (23.33 %); DRV/r + lamivudine (20%) y DRV/r + etravirine (16.67 %). Adherence was 86.79% before switching to dual therapy and 96.27% after switching. The cost savings of switching to dual therapy of these patients was € 3,635.16. CONCLUSIONS: Dual therapy with IP/r might be an effective alternative to selected treatment experienced patients compared with conventional therapy.