ABSTRACT
OBJECTIVE: Intravenous (IV) tocilizumab has been used to stop the inflammatory phase of SARS-CoV-2 infection. To preserve the largest number of IV units for this use, the Spanish Agency for Medicines and Health Products (AEMPS) carried out a controlled supply of it and recommended the change to a subcutaneous presentation (SC) of tocilizumab or sarilumab in all those patients in IV tocilizumab treatment for rheumatologic indications. The objective of this study was to evaluate the change from IV tocilizumab to SC presentation due to its controlled supply during the COVID-19 pandemic. METHODS: Retrospective observational study of adult patients (>18 years old) under treatment with IV tocilizumab follow-up by the Rheumatology Service of the Hospital 12 de Octubre. The follow-up period was 3 months (March 2020-June 2020) and 39 patients were included in the study. Variables related to the patients and their treatment were collected. A descriptive analysis of the data was carried out. RESULTS: In 69.23% (n=27) of the patients, treatment was changed to SC tocilizumab (n=23) or sarilumab (n=4). 44% of patients (n=12) switched back to their original IV tocilizumab treatment. The reasons for stopping treatment with SC tocilizumab were: drug intolerance (n=4), disease worsening (n=4), and patient preference (n=1). Regarding sarilumab, the reasons were drug intolerance (n=2) and patient preference (n=1). CONCLUSIONS: Almost half of the patients had to return to the original treatment. The main reason was intolerance to the new treatment, followed by ineffectiveness and patient preferences.
OBJETIVO: El tocilizumab intravenoso (IV) ha sido empleado para frenar la fase inflamatoria de la infección por SARS-CoV-2. Para reservar el mayor número de unidades IV para este uso, la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) realizó una distribución controlada del mismo y recomendó el cambio a una presentación subcutánea (SC), fuera tocilizumab o sarilumab, en todos aquellos pacientes en tratamiento con tocilizumab IV para indicaciones reumatológicas. El objetivo de este trabajo fue evaluar el cambio de tocilizumab IV a una presentación SC debido a su suministro controlado durante la pandemia de COVID-19. METODOS: Se realizó un estudio observacional retrospectivo de pacientes adultos (mayores de 18 años) en tratamiento con tocilizumab IV en seguimiento por el Servicio de Reumatología del Hospital 12 de octubre (Madrid). El periodo de seguimiento fue de tres meses (marzo 2020-junio 2020) y se incluyeron 39 pacientes en el estudio. Se recogieron variables relacionadas con el paciente y su tratamiento. Se realizó un análisis descriptivo de los datos. RESULTADOS: En el 69,23% (n=27) de los pacientes se cambió el tratamiento a tocilizumab SC (n=23) o sarilumab (n=4). El 44% (n=12) de los pacientes volvieron a cambiar a su tratamiento original con tocilizumab IV. Los motivos de interrupción de tratamiento con tocilizumab SC fueron: intolerancia al fármaco (n=4), empeoramiento de la enfermedad (n=4) y preferencia del paciente (n=1). Respecto al sarilumab, los motivos fueron intolerancia al fármaco (n=2) y preferencia del paciente (n=1). CONCLUSIONES: Casi la mitad de los pacientes tuvieron que volver al tratamiento original. El principal motivo fue intolerancia al nuevo tratamiento, seguido de ineficacia y preferencias del paciente.
Subject(s)
COVID-19 Drug Treatment , Rheumatic Diseases , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Humans , Pandemics , SARS-CoV-2 , Spain/epidemiology , Treatment OutcomeABSTRACT
Objetivo: El síndrome de Cogan (SC) es una enfermedad inflamatoria clasificada como vasculitis de vaso variable. Se trata de una enfermedad rara con escasas series publicadas, por lo que revisamos nuestra experiencia en 2 centros en los últimos 10 años. Material y métodos: Descripción de 7 casos diagnosticados de SC, atendiendo a los criterios de clasificación (típico o atípico), sus manifestaciones clínicas, tratamientos utilizados y sus complicaciones. Se realizó un análisis comparativo con las series y casos descritos en la literatura. Resultados: Se incluyeron 7 casos, 3 varones y 4 mujeres, con una edad media al diagnóstico de 43 años, y un tiempo de evolución medio de 47 meses. Cinco pacientes cumplían las características típicas según los criterios clásicos de 1980, siendo el resto casos atípicos, uno por ausencia de queratitis intersticial y otro por un periodo entre la aparición de clínica ocular y auditivo-vestibular mayor de 2 años. Todos recibieron inmunosupresores, siendo el más utilizado el metotrexato, seguido de la azatioprina. En 5 casos se utilizaron fármacos biológicos: infliximab en 4 ocasiones y en 2 tocilizumab. Un paciente falleció por endocarditis bacteriana y shock séptico. Conclusión: Las características de la serie presentada son similares a las publicadas hasta ahora, con diferencias clínicas fundamentalmente en la afectación de grandes vasos. Ante la escasa casuística, parece necesario la creación de registros multicéntricos para mejorar la evidencia en cuanto al manejo de pacientes con SC.(AU)
Objective: Cogan's syndrome (CS) is an inflammatory disease classified as variable vessel vasculitis. It is a rare disease with few published series, and therefore we reviewed our experience in the last ten years in two centres. Materials and methods: Description of 7 diagnosed cases of CS, according to the classification criteria (typical or atypical), their clinical manifestations, treatments used and their complications. A comparative analysis was performed with the series and cases described in the literature. Results: Seven cases were included, three men and four women, with a mean age at diagnosis of 43 years, and an average disease duration of 47 months. Five patients met the typical characteristics according to the 1980 classical criteria, the rest being atypical cases, one due to the absence of interstitial keratitis and another due to a period between the onset of ocular and auditory-vestibular clinical symptoms greater than two years. All received immunosuppressants, methotrexate being the most commonly used, followed by azathioprine. In 5 cases, biological drugs were used, infliximab in 4 times and 2 tocilizumab. One patient died from bacterial endocarditis and septic shock. Conclusion: The characteristics of the series presented are like those published to date, with clinical differences mainly in the involvement of large vessels. Given the low frequency, it seems necessary to create multicentre records to improve the evidence regarding the management of patients with CS.(AU)
Subject(s)
Humans , Male , Female , Cogan Syndrome , Hospitals , Vasculitis , Glucocorticoids , Immunosuppressive Agents , Epidemiology, Descriptive , RheumatologyABSTRACT
The complement system (CS) includes more than 50 proteins and its main function is to recognize and protect against foreign or damaged molecular components. Other homeostatic functions of CS are the elimination of apoptotic debris, neurological development, and the control of adaptive immune responses. Pathological activation plays prominent roles in the pathogenesis of most autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, dermatomyositis, and ANCA-associated vasculitis. In this review, we will review the main rheumatologic autoimmune processes in which complement plays a pathogenic role and its potential relevance as a therapeutic target.
Subject(s)
Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Complement System Proteins/immunology , Molecular Targeted Therapy , Animals , Clinical Trials as Topic , HumansABSTRACT
OBJECTIVE: Cogan's syndrome (CS) is an inflammatory disease classified as variable vessel vasculitis. It is a rare disease with few published series, and therefore we reviewed our experience in the last ten years in two centres. MATERIALS AND METHODS: Description of 7 diagnosed cases of CS, according to the classification criteria (typical or atypical), their clinical manifestations, treatments used and their complications. A comparative analysis was performed with the series and cases described in the literature. RESULTS: Seven cases were included, three men and four women, with a mean age at diagnosis of 43 years, and an average disease duration of 47 months. Five patients met the typical characteristics according to the 1980 classical criteria, the rest being atypical cases, one due to the absence of interstitial keratitis and another due to a period between the onset of ocular and auditory-vestibular clinical symptoms greater than two years. All received immunosuppressants, methotrexate being the most commonly used, followed by azathioprine. In 5 cases, biological drugs were used, infliximab in 4 times and 2 tocilizumab. One patient died from bacterial endocarditis and septic shock. CONCLUSION: The characteristics of the series presented are like those published to date, with clinical differences mainly in the involvement of large vessels. Given the low frequency, it seems necessary to create multicentre records to improve the evidence regarding the management of patients with CS.
ABSTRACT
No disponible
Subject(s)
Humans , Networks on Water Quality Monitoring/methods , Community Networks , Rheumatic Diseases/epidemiology , Rheumatic Diseases/prevention & control , Inflammation/epidemiology , Inflammation/prevention & control , Health Planning/organization & administration , Health Planning/standards , Health Resources/organization & administration , Health Resources/standardsSubject(s)
Biomedical Research/organization & administration , Rheumatic Diseases , Rheumatology/organization & administration , Biomedical Research/economics , Humans , Research Support as Topic/organization & administration , Rheumatic Diseases/diagnosis , Rheumatic Diseases/economics , Rheumatic Diseases/therapy , Rheumatology/economics , SpainABSTRACT
No disponible
Subject(s)
Humans , T-Lymphocytes/pathology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/physiopathology , Autoimmunity , Autoimmunity/immunology , Dose-Response Relationship, Immunologic , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Tumor Necrosis Factors/therapeutic useABSTRACT
El éxito de las terapias dirigidas a las células B en la artritis reumatoide (AR) sugiere que pueden ser eficaces en otras enfermedades autoinmunes mediadas por autoanticuerpos. Actualmente existen diferentes agentes en desarrollo dirigidos a diferentes dianas específicas de células B. Algunas tienen efectos funcionales y otras son citolíticas como anti-CD20 o anti-CD19 aunque la mejor estrategia está por definir. El mecanismo de acción de rituximab (anti-CD20) sugerido por los estudios en la AR es una reducción secundaria de las células plasmáticas de vida corta, productoras de autoanticuerpos localmente (sinovial), o sistémicamente. Con estas premisas es esperable que estas terapias sean eficaces en el LES, donde la hiperfunción B y los autoanticuerpos desempeñan un papel importante en su patogenia. Los ensayos clínicos han confirmado los efectos sobre las células B, algunos signos tardíos de actividad sobre la síntesis de autoanticuerpos, y sobre todo la viabilidad de estas terapias en el LES. Sin embargo, no han generado aún datos suficientes que confirmen su utilidad cuando se añaden a la terapia convencional. Aunque múltiples estudios abiertos sugieren que rituximab puede ser útil en manifestaciones refractarias, son necesarios más estudios controlados para establecer mejor sus indicaciones y estrategias de utilización el LES (AU)
Recent success of B-cell targeted therapies in rheumatoid arthritis suggests their potential efficacy for other auntoantibody-mediated autoimmune diseases. Currently, multiple agents directed toward different B-cell specific targets are under development. Although the best strategy is yet to be defined, multiple functional inhibitors or cytolitic agents such as anti-CD20 or anti-CD19 are available. According to studies in RA, the most likely mechanism of action of rituximab (anti-CD20) consists of a secondary reduction in local (synovial) or systemic autoantibody producing short-lived plasma cells. According to this data, it is expected that these therapies will be efficacious in SLE, were B-cell enhanced function and autoantibodies play relevant pathogenetic roles. Clinical trials confirm B-cell effects, delayed activity on autoantibody synthesis, and most importantly, the feasibility of these therapies to treat SLE. However, there are no sufficient data confirming their therapeutic value when added to convencional therapy. Although multiple open trials suggest that rituximab might be useful for refractory manifestations of SLE, more controlled trials are needed in order to establish the indications and strategies of its use in SLE (AU)
Subject(s)
Humans , Lupus Erythematosus, Systemic/drug therapy , B-Lymphocytes , Immunosuppressive Agents/therapeutic use , Autoantibodies , Antigens, CD20ABSTRACT
Recent success of B-cell targeted therapies in rheumatoid arthritis suggests their potential efficacy for other auntoantibody-mediated autoimmune diseases. Currently, multiple agents directed toward different B-cell specific targets are under development. Although the best strategy is yet to be defined, multiple functional inhibitors or cytolitic agents such as anti-CD20 or anti-CD19 are available. According to studies in RA, the most likely mechanism of action of rituximab (anti-CD20) consists of a secondary reduction in local (synovial) or systemic autoantibody producing short-lived plasma cells. According to this data, it is expected that these therapies will be efficacious in SLE, were B-cell enhanced function and autoantibodies play relevant pathogenetic roles. Clinical trials confirm B-cell effects, delayed activity on autoantibody synthesis, and most importantly, the feasibility of these therapies to treat SLE. However, there are no sufficient data confirming their therapeutic value when added to convencional therapy. Although multiple open trials suggest that rituximab might be useful for refractory manifestations of SLE, more controlled trials are needed in order to establish the indications and strategies of its use in SLE.
ABSTRACT
La interleucina (IL) 6 fue identificada en 1986 como un factor producido por los linfocitos T, con efectos estimuladores del crecimiento y síntesis de inmunoglobulinas en los linfocitos B. Pertenece a una amplia familia de citocinas que comparten el receptor de membrana gp130, mediador de una señal específica de activación del sistema Jak/STAT3 con amplios efectos en la expresión de genes proinflamatorios e inmunorreguladores. De forma más prominente que otras citocinas, la IL-6 media potentes acciones sistémicas en órganos distantes de su origen local inflamatorio. Las más específicas afectan a la hematopoyesis y la síntesis hepática de reactantes de fase aguda. Su potencial actividad proinflamatoria y de destrucción articular, junto con su implicación en la inmunorregulación T y B, la convirtió en una diana terapéutica atractiva, confirmada por el éxito de su antagonista tocilizumab en la artritis reumatoide (AR). Aunque son necesarios estudios más amplios sobre la participación de la IL-6 en la fisiopatología de la AR, numerosos datos indirectos permiten situarla en una posición muy relevante (AU)
Interleukin (IL) 6 was identified in 1986 as a factor produced by T lymphocytes, that mediates growth and immunoglobulin synthesis on B lymphocytes. IL-6 is a member of a large cytokine family sharing a gp130 membrane receptor. This receptor mediates specific Jak/STAT3 activation, which induces widespread expression of pro-inflammatory and immunoregulatory genes. IL-6 mediates potent systemic responses, in organs distant from its local inflammatory sources, in a prominent fashion compared to other cytokines. Most specific effects involve hematopoiesis and hepatic acute phase reactants synthesis. IL-6 became a rheumatoid arthritis (RA) target due to its pro-inflammatory and joint destructive potential, as well as its participation in T and B immunoregulation. The therapeutic success of tocilizumab has confirmed IL-6 as an RA target. Although additional studies on the participation of IL-6 in RA physiopathology are needed, a number of indirect data point to a relevant position in this setting (AU)
Subject(s)
Humans , Interleukin-6 , Arthritis, Rheumatoid/physiopathology , Antibodies, Monoclonal/therapeutic use , Immunosuppressive Agents/therapeutic use , CytokinesABSTRACT
Interleukin (IL) 6 was identified in 1986 as a factor produced by T lymphocytes, that mediates growth and immunoglobulin synthesis on B lymphocytes. IL-6 is a member of a large cytokine family sharing a gp130 membrane receptor. This receptor mediates specific Jak/STAT3 activation, which induces widespread expression of pro-inflammatory and immunoregulatory genes. IL-6 mediates potent systemic responses, in organs distant from its local inflammatory sources, in a prominent fashion compared to other cytokines. Most specific effects involve hematopoiesis and hepatic acute phase reactants synthesis. IL-6 became a rheumatoid arthritis (RA) target due to its pro-inflammatory and joint destructive potential, as well as its participation in T and B immunoregulation. The therapeutic success of tocilizumab has confirmed IL-6 as an RA target. Although additional studies on the participation of IL-6 in RA physiopathology are needed, a number of indirect data point to a relevant position in this setting.
ABSTRACT
No disponible
