Semaphorin3B promotes an anti-inflammatory and pro-resolving phenotype in macrophages from rheumatoid arthritis patients in a MerTK-dependent manner.

Previous works from our group show that Semaphorin3B (Sema3B) is reduced in RA and plays a protective role in a mouse arthritis model. In turn, MerTK plays a protective function in murine arthritis models, is expressed by synovial tissue macrophages and is linked to remission in patients with RA. In this study, we examined the role of Sema3B in the phenotypic characteristics of RA macrophages and the implication of MerTK. Peripheral blood monocytes from RA patients were differentiated into IFN-γ (RA MØIFN-γ) or M-CSF (RA MØM-CSF) macrophages and stimulated with LPS, Sema3B or their combination. Alternatively, RA fibroblast like synoviocytes (FLS) were stimulated with RA MØIFN-γ and RA MØM-CSF supernatants. Gene expression was determined by qPCR and protein expression and activation by flow cytometry, ELISA and western blot. Sema3B down-regulated the expression of pro-inflammatory mediators, in both RA MØIFN-γ and RA MØM-CSF. We observed a similar reduction in RA FLS stimulated with the supernatant of Sema3B-treated RA MØIFN-γ and RA MØM-CSF. Sema3B also modulated cell surface markers in macrophages towards an anti-inflammatory phenotype. Besides, MerTK expression and activation was up-regulated by Sema3B, just as GAS6 expression, Resolvin D1 secretion and the phagocytic activity of macrophages. Importantly, the inhibition of MerTK and neuropilins 1 and 2 abrogated the anti-inflammatory effect of Sema3B. Our data demonstrate that Sema3B modulates the macrophage characteristics in RA, inducing a skewing towards an anti-inflammatory/pro-resolving phenotype in a MerTK-dependant manner. Therefore, here we identify a new mechanism supporting the protective role of Sema3B in RA pathogenesis.

Secukinumab como tratamiento biológico en la artritis psoriásica en práctica clínica real / Secukinumab as Biological Treatment for Psoriatic Arthritis in Real Clinical Practice

Introducción: Los ensayos clínicos de secukinumab han demostrado su eficacia y seguridad en la artritis psoriásica como biológico de primera opción o tras respuesta inadecuada a otros tratamientos biológicos. Objetivo: Analizar la eficacia y seguridad de secukinumab en la artritis psoriásica periférica durante 12 meses en práctica clínica real. Material y métodos: Se incluyó a pacientes con artritis psoriásica periférica activa que iniciaron tratamiento con secukinumab según ficha técnica. Se evaluó la eficacia y seguridad desde la situación basal hasta los 12 meses, comparando la respuesta de pacientes naive y no naive al biológico. Resultados: Se incluyó a 76 pacientes (22 naive y 54 no naive al biológico) con una edad de 51,9 años (10,3) y una duración de la enfermedad de 9,5 años (7,1). El 31,6% con dactilitis, el 51,3% con entesitis y el índice DAPSA basal fue 19 (9,8). La tasa de retención fue elevada: 90,9% en naive y 81,5% en no naive, y el porcentaje de pacientes con un DAPSA menor o igual a 14 fue mayor en pacientes naive, incluso después de ajustar por edad, sexo y fármacos modificadores del curso de la enfermedad (p=0,016). Los datos de seguridad fueron similares a los descritos en los ensayos clínicos. Conclusiones: Secukinumab es eficaz y seguro en el tratamiento a 12 meses en la artritis psoriásica periférica activa en la práctica clínica real, tras respuesta inadecuada a los iTNF o como primer biológico.(AU)

Introduction: Clinical trials of secukinumab have demonstrated their efficacy and safety in psoriatic arthritis as biological first choice or after inadequate response to other biological treatments. Objective: To analyze the efficacy and safety of secukinumab in peripheral psoriatic arthritis over 12 months in real clinical practice. Material and methods: Patients with active peripheral psoriatic arthritis who started treatment with secukinumab according to the technical specifications were included. Efficacy and safety were evaluated from baseline to 12 months comparing naive and non-naive to biological therapy patients. Results: A total of 76 patients were included (22 naive and 54 non-naive to biological) with an age of 51.9 years (10.3) and duration of the disease of 9.5 years (7.1). Of them, 31.6% with dactylitis, 51.3% with enthesitis and the baseline DAPSA was 19.0 (9.8). The retention rate was high, 90.9% in naive and 81.5% in non-naïve patients, and the percentage of patients with a DAPSA less than or equal to 14 was higher in the naive patients even after adjusting for age, sex and FAMEsc (P=.016). The safety data were similar to those described in the clinical trials. Conclusions: Secukinumab is effective and safe in 12-month treatment in peripheral active psoriatic arthritis in real clinical practice, after inadequate response to TNF or as first biological treatment.(AU)

Secukinumab as Biological Treatment for Psoriatic Arthritis in Real Clinical Practice. / Secukinumab como tratamiento biológico en la artritis psoriásica en práctica clínica real.

INTRODUCTION: Clinical trials of secukinumab have demonstrated their efficacy and safety in psoriatic arthritis as biological first choice or after inadequate response to other biological treatments. OBJECTIVE: To analyze the efficacy and safety of secukinumab in peripheral psoriatic arthritis over 12 months in real clinical practice. MATERIAL AND METHODS: Patients with active peripheral psoriatic arthritis who started treatment with secukinumab according to the technical specifications were included. Efficacy and safety were evaluated from baseline to 12 months comparing naive and non-naive to biological therapy patients. RESULTS: A total of 76 patients were included (22 naive and 54 non-naive to biological) with an age of 51.9 years (10.3) and duration of the disease of 9.5 years (7.1). Of them, 31.6% with dactylitis, 51.3% with enthesitis and the baseline DAPSA was 19.0 (9.8). The retention rate was high, 90.9% in naive and 81.5% in non-naïve patients, and the percentage of patients with a DAPSA less than or equal to 14 was higher in the naive patients even after adjusting for age, sex and FAMEsc (P=.016). The safety data were similar to those described in the clinical trials. CONCLUSIONS: Secukinumab is effective and safe in 12-month treatment in peripheral active psoriatic arthritis in real clinical practice, after inadequate response to TNF or as first biological treatment.