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.

A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF.

BACKGROUND: The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. MATERIAL AND METHODS: A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. RESULTS: No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). CONCLUSION: FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.

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.

Uso de pertuzumab y desensibilización a docetaxel en paciente oncológico; a propósito de un caso / Use of pertuzumab and docetaxel desensitization in oncological patient; apropos of a case

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Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis.

OBJECTIVES: As the role of polymorphisms in death receptors (DRs) such as Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains unknown, we evaluated the association between TRAILR1 and TNFR1A gene polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with TNFα blockers. METHODS: One hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNFα therapy (RA: 75 infliximab, 8 etanercept, 7 adalimumab. PsA: 27 infliximab, 19 etanercept, 9 adalimumab) were genotyped for TRAILR1 and TNFR1A polymorphisms by allelic discrimination. The response to anti-TNFα was assessed by EULAR criteria. RESULTS: In RA, the TRAILR1 CC genotype was associated with a better response after 3 and 6 months of anti-TNFα treatment (CC: 91.7% vs. CG/GG: 62.2%; P=0.019, and CC: 82.6% vs. CG/GG: 56.1%; P=0.019, respectively). Similar results were observed in only infliximab-treated RA patients. With respect to the TNFR1A polymorphism, there was an association between the AA genotype and a poorer response at 3 months in RA patients (AA: 39.3% vs. AG/GG: 19.0%; P=0.04). In PsA, TRAILR1 CC genotype was only associated with EULAR response to infliximab at 6 months (CC: 71.4% vs CG/GG: 50%P=0.048). In contrast to RA, the TNFR1 polymorphism in PsA was associated with a better response at 3 months (AA 88% vs AG/GG 58.9%; P=0.04). CONCLUSIONS: This study provides the first evidence that a polymorphism in TRAILR1 influences the response to anti-TNFα therapy in RA and also suggests that TNFR1A polymorphism may have opposing effects on the response to anti-TNFα in RA and PsA.