Persistencia de secukinumab en pacientes con psoriasis, artritis psoriásica y espondilitis anquilosante / Persistence of secukinumab in patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis

OBJETIVO: Determinar la persistencia del tratamiento con secukinumab en sus diferentes indicaciones. MÉTODO: Estudio descriptivo, observacional, retrospectivo donde se incluyeron los pacientes adultos tratados con secukinumab en sus diferentes indicaciones desde su comercialización en noviembre de 2015 hasta octubre de 2019. Las variables recogidas fueron sexo, edad, diagnóstico, fecha de inicio, línea de tratamiento, número de pacientes que habían suspendido el tratamiento y motivo de suspensión, persistencia global a los 12 meses, distribución de pacientes y persistencia según indicación, línea de tratamiento y motivo de suspensión. RESULTADOS: Han sido tratados con secukinumab 143 pacientes, de los que 104 llevaban en tratamiento 12 o más meses. La media de edad fue 49,8 ± 12,6 años; 52,9% fueron hombres. Suspendieron el tratamiento 56 pacientes (53,8%) con una media de duración del mismo de 12,7 ± 10,2 meses. El resto (n = 48) continuaban con una media de duración de 25,7 ± 9,9 meses en el momento del corte del estudio. La persistencia global a los 12 meses fue de 10,0 ± 3,3 meses con una tasa de discontinuación a los 12 meses del 31,7%. La persistencia por patología a los 12 meses fue 10,7 ± 2,9 para los pacientes con psoriasis, 9,7 ± 3,4 meses para los pacientes con artritis psoriásica y 8,8 ± 3,8 para los pacientes con espondilitis anquilosante. De los 48 pacientes que continuaban en tratamiento, 22 (45,8%) están recibiendo el fármaco en primera línea. De los 56 pacientes que discontinuaron, 15 (26,8%) lo hicieron por fallo primario (persistencia 3,8 ± 1,1 meses) y 27 (48,2%) por fallo secundario (persistencia 18,6 ± 9,6 meses). La persistenciaen los pacientes que continuaban en tratamiento fue superior en psoriasis (28,8 ± 10,3 meses) y en los que suspendieron por fallo secundario fue superior en espondilitis anquilosante (28,0 ± 4,2 meses). En los pacientes de primera línea, la persistencia fue inferior al resto, siendo 21,2 ± 7,2 meses, 3,5 ± 0,5 meses y 8,3 ± 2,5 meses, si continuaban en tratamiento, presentaron fallo primario o fallo secundario, respectivamente. CONCLUSIONES: Nuestros datos muestran una persistencia ligeramente superior en pacientes con psoriasis y una menor tasa de discontinuación en aquellos pacientes sin exposición previa a un tratamiento biológico. Se necesitan estudios a largo plazo que lo confirmen y conocer los factores que pueden influir en la persistencia del secukinumab

OBJECTIVE: To determine persistence of treatment with secukinumab across its different indications. METHOD: This is a retrospective descriptive observational study including adult patients treated with secukinumab in its different indications from the drug's introduction in November 2015 to October 2019. The variables included were sex; age; diagnosis; initiation date; line of treatment; number of patients who discontinued treatment and reason for discontinuation; overall persistence at 12 months; distribution of patients; and persistence according to indication, line of treatment and reason for suspension. RESULTS: One-hundred forty-three patients were started on secukinumab, but only patients who had been in treatment at least 12 months before the end of the study were included. Mean patient age was 49.8 years (±12.6); 52.9% were men. Fifty-six patients (53.8%) had discontinued treatment by the end of the study, with a mean duration of treatment of 12.7 months (±10.2). The other patients (n = 48) continued with their therapy. Mean duration of treatment in these patients was 25.7 months (±9.9). Overall persistence at 12 months was 10.0 months (±3.3) with a discontinuation rate at 12 months of 31.7%. Persistence at 12 months was 10.7 months (±2.9) for patients with psoriasis, 9.7 months (±3.4) for patients with psoriatic arthritis, and 8.8 months (±3.8) for those with ankylosing spondylitis. Of the 48 patients who continued with their treatment after completion of the study, 22 (45.8%) received the drug as first-line treatment. Of the 56 discontinuations, 15 (26.8%) were due to primary failure (persistence: 3.8 months [±1.1]) and 27 (48.2%) were due to secondary failure (persistence: 18.6 months [±9.6]). Persistence in patients who continued treatment was higher in psoriasis (28.8 months [±10.3]). In those who discontinued due to secondary failure it was higher in the group with ankylosing spondylitis (28.0 months [±4.2]). Persistence among patients on first-line secukinumab was higher than for other patients: 21.2 months (±7.2) if they stayed on treatment, 3.5 months (±0.5) if they presented with primary treatment failure, and 8.3 months (±2.5) in those with secondary treatment failure. CONCLUSIONS: Our data show slightly higher persistence levels in patients with psoriasis and lower discontinuation rates in those without previous exposure to biological therapy. Long-term studies are needed to confirm these findings and to gain a better understanding of the factors that can influence persistence of secukinumab

Persistence of secukinumab in patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis.

OBJECTIVE: To determine persistence of treatment with secukinumab across its different indications. METHOD: This is a retrospective descriptive observational study including adult patients treated with secukinumab in its different  indications from the drug's introduction in November 2015 to October  2019. The variables included were sex; age; diagnosis; initiation date; line of treatment; number of patients who discontinued treatment and reason  for discontinuation; overall persistence at 12 months; distribution of  patients; and persistence according to indication, line of treatment and  reason for suspension. RESULTS: One-hundred forty-three patients were started on secukinumab, but only patients who had been in treatment at least 12  months before the end of the study were included. Mean patient age was  49.8 years (±12.6); 52.9% were men. Fifty-six patients (53.8%) had  discontinued treatment by the end of the study, with a mean duration of  treatment of 12.7 months (±10.2). The other patients (n = 48) continued  with their therapy. Mean duration of treatment in these patients was 25.7  months (±9.9). Overall persistence at 12 months was 10.0 months (±3.3)  with a discontinuation rate at 12 months of 31.7%. Persistence at 12  months was 10.7 months (±2.9) for patients with psoriasis, 9.7 months  (±3.4) for patients with psoriatic arthritis, and 8.8 months (±3.8) for  those with ankylosing spondylitis. Of the 48 patients who continued with  their treatment after completion of the study, 22 (45.8%) received the  drug as first-line treatment. Of the 56 discontinuations, 15 (26.8%) were  due to primary failure (persistence:  3.8 months [±1.1]) and 27 (48.2%)  were due to secondary failure (persistence: 18.6 months [±9.6]).  Persistence in patients who continued treatment was higher in psoriasis  (28.8 months [±10.3]). In those who discontinued due to secondary  failure it was higher in the group with ankylosing spondylitis (28.0 months  [±4.2]). Persistence among patients on first-line secukinumab was higher  than for other patients: 21.2 months (±7.2) if they stayed on treatment,  3.5 months (±0.5) if they presented with primary treatment failure, and  8.3 months (±2.5) in those with secondary treatment failure. CONCLUSIONS: Our data show slightly higher persistence levels in patients with psoriasis and lower discontinuation rates in those without  previous exposure to biological therapy. Long-term studies are needed to  confirm these findings and to gain a better understanding of the factors  that can influence persistence of secukinumab.

Objetivo: Determinar la persistencia del tratamiento con secukinumab en  sus diferentes indicaciones.Método: Estudio descriptivo, observacional, retrospectivo donde se incluyeron los pacientes adultos tratados con secukinumab en sus  diferentes indicaciones desde su comercialización en noviembre de 2015  hasta octubre de 2019. Las variables recogidas fueron sexo, edad,  diagnóstico, fecha de inicio, línea de tratamiento, número de pacientes que habían suspendido el tratamiento y motivo de suspensión, persistencia  global a los 12 meses, distribución de pacientes y persistencia según  indicación, línea de tratamiento y motivo de suspensión.Resultados: Han sido tratados con secukinumab 143 pacientes, de los  que 104 llevaban en tratamiento 12 o más meses. La media de edad fue  49,8 ± 12,6 años; 52,9% fueron hombres. Suspendieron el tratamiento 56 pacientes (53,8%) con una media de duración del mismo de 12,7 ± 10,2  meses. El resto (n = 48) continuaban con una media de duración de 25,7  ± 9,9 meses en el momento del corte del estudio. La persistencia global a  los 12 meses fue de 10,0 ± 3,3 meses con una tasa de discontinuación a  los 12 meses del 31,7%. La persistencia por patología a los 12 meses fue  10,7 ± 2,9 para los pacientes con psoriasis, 9,7 ± 3,4 meses para los  pacientes con artritis psoriásica y 8,8 ± 3,8 para los pacientes con  espondilitis anquilosante. De los 48 pacientes que continuaban en  tratamiento, 22 (45,8%) están recibiendo el fármaco en primera línea. De  los 56 pacientes que discontinuaron, 15 (26,8%) lo hicieron por fallo  primario (persistencia 3,8 ± 1,1 meses) y 27 (48,2%) por fallo secundario  (persistencia 18,6 ± 9,6 meses). La persistencia en los pacientes que  continuaban en tratamiento fue superior en psoriasis (28,8 ± 10,3 meses)  y en los que suspendieron por fallo secundario fue superior en espondilitis  anquilosante (28,0 ± 4,2 meses). En los pacientes de primera línea, la  persistencia fue inferior al resto, siendo 21,2 ± 7,2 meses, 3,5 ± 0,5  meses y 8,3 ± 2,5 meses, si continuaban en tratamiento, presentaron fallo primario o fallo secundario, respectivamente.Conclusiones: Nuestros datos muestran una persistencia ligeramente superior en pacientes con psoriasis y una menor tasa de  discontinuación en aquellos pacientes sin exposición previa a un  tratamiento biológico. Se necesitan estudios a largo plazo que lo confirmen y conocer los factores que pueden influir en la persistencia del  secukinumab.

Diseño y adecuación de una solución gluco-proteica con calcio a las necesidades de recién nacidos pre-término / Design and adequacy of a glycoprotein solution with calcium for the needs of preterm newborn infants

RESUMEN Nuestro objetivo fue diseñar una solución gluco-proteica estandarizada con aporte de calcio y evaluar su adecuación en recién nacidos pre-término en las primeras horas de vida. Método: Se realizó un estudio piloto entre febrero de 2016 y febrero de 2017 en el que se diseñaron dos soluciones gluco-proteicas (vía central y vía periférica) para ser utilizadas en recién nacidos en las primeras horas de vida, que se adaptasen a los requerimientos de todos los recién nacidos en función del ritmo de infusión. Se diseñaron según las recomendaciones existentes y se elaboró el protocolo normalizado de trabajo para describir el proceso de elaboración y los controles de calidad requeridos (visual, gravimétrico y microbiológico). Se monitorizo la respuesta de esta solución gluco-proteica en recién nacidos pre-término. Resultados principales: Se elaboraron 54 lotes de soluciones glucoproteicas por vía central y 52 por vía periférica que se administraron a 47 recién nacidos pre-término sin presentarse complicaciones ni efectos adversos. Conclusiones: la concentración de calcio de la solución gluco-proteica se adapta a las necesidades de la mayoría de los recién nacidos pre-término. La elaboración de soluciones estandarizadas disminuye la carga de trabajo del servicio de farmacia y los costes económicos asociados.

ABSTRACT Our aim was to design a standardized glycoprotein solution with calcium and evaluate adequacy for preterm newborn infants in the first hours of life. Method: Pilot study conducted between February 2016 and February 2017. Two glycoprotein solutions were designed (central and peripheral administration) to be used in newborns in the first hours of life to provide the requirements of all newborns depending on the infusion rhythm. The solutions were designed according to current recommendations, the standard operating procedure was drawn up describing the elaboration process, and the quality controls required (visual, gravimetric and microbiological). The response of this solution in preterm newborns was monitored. Main results: During the study, 54 batches of central glycoprotein solutions and 52 of peripheral glycoprotein solutions were prepared and administered to 47 preterm newborns without complications or side effects in relation to their administration. Conclusions: The concentration of calcium used in the glycoprotein solution formulation was adapted to the requirements of most preterm newborns. The development of standardized solutions reduces the workload of the pharmacy service and the associated economic costs.

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®. RESULTS: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01-16.34), age (OR 1.43; 95% CI 1.03-2.00), and body mass index (OR 4.05; 95% CI 1.21-13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables.

Reasons for Discontinuation and Adverse Effects of TNFα Inhibitors in a Cohort of Patients With Rheumatoid Arthritis and Ankylosing Spondylitis.

BACKGROUND: The introduction of anti-tumor necrosis factor α (anti-TNFα) drugs has improved the clinical outcomes in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, these drugs may cause adverse effects that motivate a change in or discontinuation of the treatment. OBJECTIVE: To evaluate the causes of discontinuation or changes in the dosage regimen in a cohort of patients with RA and AS treated with infliximab, adalimumab, etanercept, and golimumab under clinical practice conditions. METHODS: This was a retrospective observational study that included patients with RA or AS treated with anti-TNFα drugs between 2008 and 2013. Changes in the dosage regimen, reasons for treatment discontinuation, and adverse effects were recorded and analyzed. Time to discontinuation was estimated using Kaplan-Meier survival analysis. RESULTS: A total of 123 patients with RA and 93 patients with AS were treated with anti-TNFα therapy. During the study, 55.3% of RA patients and 41.7% of AS patients had stopped the treatment. The most frequent changes were modifications in the dosing, and the most frequent adverse effects were reactions after the infusion or injection (53.8% and 66.7% in RA and AS, respectively). Drug survival of etanercept in RA (67.9%) is greater than for adalimumab and infliximab, whereas drug survival of infliximab in AS (70.0%) is greater than for etanercept and adalimumab at 5 years, although there were no significant differences ( P = 0.098 in RA and 0.194 in AS). CONCLUSIONS: The main cause of discontinuation of anti-TNFα is therapeutic failure in both diseases. Etanercept and infliximab have the best survival rates in RA and AS, respectively.

Experiencia del uso fuera de indicación de Eltrombopag en el tratamiento de la trombocitopenia asociada a tumores sólidos / Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors

Objetivo: Describir los resultados del uso fuera de indicación de eltrombopag en pacientes con trombocitopenia limitante de tratamiento quimioterápico y tumores sólidos. Método: Estudio observacional retrospectivo en el que se incluyeron todos los pacientes con tumores sólidos tratados con eltrombopag por trombocitopenia durante el tratamiento con quimioterapia entre enero de 2012 y diciembre de 2014. Resultados: Seis pacientes, con tumores sólidos y trombocitopenia limitante de tratamiento, recibieron eltrombopag durante el periodo de estudio con una disminución en el retraso de ciclos de quimioterapia (4,83 ± 4,79 ciclos retrasados antes del inicio de eltrombopag vs 2,50 ± 4,32 ciclos durante el tratamiento con eltrombopag, p=0,492) y un aumento en el porcentaje de dosis real administrada (89,29 ± 13,36% vs 91,43 ± 10,69%, p=0,682). Así mismo, se produjo un aumento en el nadir de plaquetas (55,29 ± 16,45x109 /L vs 76,14 ± 36,38x109 /L, p=0,248) sin requerir en ningún paciente soporte transfusional con plaquetas durante el tratamiento con eltrombopag. Conclusiones: eltrombopag ha resultado ser una alternativa de tratamiento para pacientes con trombocitopenia limitante de tratamiento con quimioterapia, siendo necesarios ensayos clínicos con mayor número de pacientes que confirmen estos resultados (AU)

Purpose: To describe the results of the off-label use of eltrombopag in patients with solid tumors and thrombocytopenia that limits chemotherapy. Methods: Retrospective observational study including all patients with solid tumors who were treated with eltrombopag for thrombocytopenia during the chemotherapy treatment between January 2012 and December 2014. Results: Six patients, with solid tumors and thrombocytopenia that limits chemotherapy treatment, received eltrombopag during the study and it was observed a decrease in the delay of chemotherapy cycles (4.83 ± 4.79 delayed cycles before starting eltrombopag vs 2.50 ± 4.32 delayed cycles during the treatment with eltrombopag, p=0.492) and an increase in the percentage of administrated dosage (89.29 ± 13.36% vs 91.43 ± 10.69%, p=0.682). Also, there was an increase in platelet nadir (55.29 ± 16.45x109 /L vs 76.14 ± 36.38x109 /L, p=0.248) without platelet transfusion support in any patient during treatment with eltrombopag. Conclusions: eltrombopag has resulted to be an alternative in the treatment of patients with thrombocytopenia that limits chemotherapy, clinical trials with more number or patients are needed to confirm these results (AU)

[Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors]. / Experiencia del uso fuera de indicación de Eltrombopag en el tratamiento de la trombocitopenia asociada a tumores sólidos.

PURPOSE: To describe the results of the off-label use of eltrombopag in patients with solid tumors and thrombocytopenia that limits chemotherapy. METHODS: Retrospective observational study including all patients with solid tumors who were treated with eltrombopag for thrombocytopenia during the chemotherapy treatment between January 2012 and December 2014. RESULTS: Six patients, with solid tumors and thrombocytopenia that limits chemotherapy treatment, received eltrombopag during the study and it was observed a decrease in the delay of chemotherapy cycles (4.83 ± 4.79 delayed cycles before starting eltrombopag vs 2.50 ± 4.32 delayed cycles during the treatment with eltrombopag, p=0.492) and an increase in the percentage of administrated dosage (89.29 ± 13.36% vs 91.43 ± 10.69%, p=0.682). Also, there was an increase in platelet nadir (55.29 ± 16.45x109/L vs 76.14 ± 36.38x109/L, p=0.248) without platelet transfusion support in any patient during treatment with eltrombopag. CONCLUSIONS: eltrombopag has resulted to be an alternative in the treatment of patients with thrombocytopenia that limits chemotherapy, clinical trials with more number or patients are needed to confirm these results.

Objetivo: Describir los resultados del uso fuera de indicación de eltrombopag en pacientes con trombocitopenia limitante de tratamiento quimioterápico y tumores sólidos. Método: Estudio observacional retrospectivo en el que se incluyeron todos los pacientes con tumores sólidos tratados con eltrombopag por trombocitopenia durante el tratamiento con quimioterapia entre enero de 2012 y diciembre de 2014. Resultados: Seis pacientes, con tumores sólidos y trombocitopenia limitante de tratamiento, recibieron eltrombopag durante el periodo de estudio con una disminución en el retraso de ciclos de quimioterapia (4,83 ± 4,79 ciclos retrasados antes del inicio de eltrombopag vs 2,50 ± 4,32 ciclos durante el tratamiento con eltrombopag, p=0,492) y un aumento en el porcentaje de dosis real administrada (89,29 ± 13,36% vs 91,43 ± 10,69%, p=0,682). Así mismo, se produjo un aumento en el nadir de plaquetas (55,29 ± 16,45x109/L vs 76,14 ± 36,38x109/L, p=0,248) sin requerir en ningún paciente soporte transfusional con plaquetas durante el tratamiento con eltrombopag. Conclusiones: eltrombopag ha resultado ser una alternativa de tratamiento para pacientes con trombocitopenia limitante de tratamiento con quimioterapia, siendo necesarios ensayos clínicos con mayor número de pacientes que confirmen estos resultados.