Concerns over safety profiles of tumor necrosis factor (TNF)-alfa inhibitors have been raised. The purpose of this study was to clarify the adverse events associated with TNF-alfa inhibitors using a ...spontaneous reporting system database.
A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between 2004 and 2017 were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated.
Among the 34,031 reports of adverse events associated with TNF-alfa inhibitors, 65.8% were women, who were frequently in their 60s (28.2%). Signals were detected for pneumonia (ROR, 5.36; 95% CI, 5.14-5.6), interstitial lung disease (ROR, 2.04; 95% CI, 1.95-2.15), pneumocystis jirovecii pneumonia (ROR, 11.8; 95% CI, 11.1-12.5), and herpes zoster (ROR, 6.4; 95% CI, 5.92-6.91) for TNF-alfa inhibitors as a class. There was variability in their signal strength across individual TNF-alfa inhibitors.
The strength of the associations of TNF-alfa inhibitors with adverse events is variable, and further studies are required to evaluate the identified signals.
The aim of this study was to determine whether there is any association with anti-tumor necrosis factor (TNF) agent administration and development of new-onset inflammatory bowel disease (IBD) in ...ankylosing spondylitis (AS) patients.
Records of the patients who met 1984 modified New York criteria for AS between 1998 and 2016 at Rheumatology Department were evaluated retrospectively and data about the patients, IBD properties and medication were obtained.
Among 420 patients, 310 were male, the average age was 42.9 ± 1.3 years, average disease duration was 16.7 ± 10.4 years. Anti-TNF agents were in use by 154 patients, 52 patients were receiving etanercept (ETN), infliximab (INF), adalimumab (ADA), and golimumab (GO) treatments were ongoing in 50, 41, and 11 patients, respectively. New-onset IBD developed in 10 patients; 3 from the group treated with non-anti-TNF drugs (1.1%) and 7 from the group treated with anti-TNF agents (4.5%) (p = 0.042). No significant difference was detected between three anti-TNF agent forms in relation with the risk of IBD onset. In AS patients, existence of familial AS (OR 4.69 (95%CI 1.28-17.19, p = 0.020) and anti-TNF agent treatment (OR 4.17 (95%CI 1.06-16.38, p = 0.041) were independent risk factors for new-onset IBD development.
Despite the increased risk of new-onset IBD development during the course of AS, paradoxical response to anti-TNF drugs must also be considered as a source that triggers onset of IBD.
The aim of the study was to assess the long-term efficacy and safety of Infliximab therapy in the treatment of patients with Behçet’s disease refractory to standard immunosuppressive agents. ...Twenty-one patients that did not respond to corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate, azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued at least 4 weeks prior baseline visit. The patients received three infusions of 5 mg/kg Infliximab (at weeks 0, 2 and 6) and then infusions of 5 mg/kg Infliximab every 8 weeks. At each visit data on clinical symptoms, response to therapy and adverse events were collected. The primary outcome of interest was to assess the clinical efficacy (total or partial recovery) of infliximab. Secondary end points were to evaluate quality of life and to monitor the safety of the drug. Eighteen patients achieved a total remission. Two patients achieved a partial remission and relapsed after 3 months from discontinuation of therapy. Infliximab was well tolerated throughout the study. A case of non-Hodgkin lymphoma was observed within 6 months. Minor side effects were headache, dizziness, tachycardia that regressed spontaneously and did not entail interruption. Anti-nuclear antibodies were not detected during the period of observation.
El factor de necrosis tumoral (TNF) es un importante mediador de las reacciones inflamatorias y parece jugar un rol central en la patogénesis de varias enfermedades inflamatorias crónicas incluyendo ...la periodontitis. Se ha demostrado que existen diferentes tasas de síntesis de TNF alfa in vitro e in vivo entre los individuos, por lo que puede asociarse con la presencia de cierto polimorfismo genético. El presente estudio tiene la finalidad de estudiar el grado de polimorfismo del gen TNF-alfa (-308G/A) en una muestra de pacientes peruanos adultos y analizar la relación con los procesos periodontales severos. Para el estudio se colectaron 81 muestras de sangre con anticoagulante EDTA de personas comprendidas entre 25 y 52 años (promedio 47.5 ± 7.4). De los cuales 11 son de personas con procesos periodontales severos (promedio 35.2 ± 2.3). Se encontró una frecuencia mayor del genotipo GG (alelo G para el gen TNF-alfa-308) del 82.86% en personas sanas y 63.63% en personas con procesos periodontales. Mientras que el genotipo AA (alelo A para el gen TNF-alfa-308) que se relaciona a un mayor incremento de síntesis de TNF-alfa, fue de 18.8%, siendo un valor no muy significativo según la prueba chi-cuadrado. Los resultados están de acuerdo a algunos trabajos que encuentran asociación directa entre el polimorfismo del gen TNF-alfa con los procesos periodontales, pero no con otros que si lo asocian. Dado que la periodontitis es considerada una enfermedad multifactorial se discute el polimorfismo de TNF-alfa -308 (G/A) en pacientes peruanos.
In this study, the effect of mesalazine was studied on TNF alpha IL-1 beta, IL-6, and C-reactive protein (CRP) levels and inflammatory changes in rat lungs with experimental peritonitis.
In total, 24 ...male Sprague-Dawley rats weighing 250-280 g were used in the study.The rats were divided into three groups based on no irrigation or irrigation with isotonic solution or mesalazine. Secondary peritonitis was generated by cecum penetrations. Group I, no irrigation was given after the development of peritonitis; Group II, irrigation was performed using isotonic solution 24 h after the development of peritonitis.
irrigation was performed using mesalazine 24 h after the development of peritonitis. Blood samples were taken in the 48
hour for measuring TNF alpha, IL-1 beta, IL-6, and CRP levels. Lung tissue samples were taken for examining the effect of mesalazine in the development of systemic sepsis.
TNF alpha, IL-1 beta, and CRP levels were significantly low in Group III than in the other groups (p<0.005). In the histologic examination, leucocyte infiltration in the lung was found low in Group III.
TNF alpha, IL-1 beta, and CRP levels and leucocyte infiltration in the lung were found to be low in rats that were administered peritoneal irrigation using mesalazine after the development of secondary peritonitis. Peritoneal irrigation using mesalazine may be useful in patients requiring surgery due to secondary peritonitis.
We aimed to find out if mucosal TNF-α (m-TNF-α) levels have predictive impact on anti-TNF treatment response in Crohn's disease (CD).
TNF-alpha values were determined with immunohistochemical ...staining of intestinal biopsies taken from 35 subjects on anti-TNF treatment for CD and 25 controls. Correlation between m-TNF-α levels and anti-TNF treatment were evaluated.
m-TNF-α levels were determined higher in CD group (28.0±8.9 vs 5.8±2.1; P<0.001). m-TNF-α levels were lower in CD patients who were hospitalized (23.0±8.7 vs. 30.3±8.1; P=0.024). Although not to a statistically significant level, favorable parameters such as clinical remission (28.5±8.0 vs. 26.4±11.8, p=0.419) and mucosal healing (29.9±8.2 vs. 23.9±9.2, p=0.097) were increased in patients with high m-TNF-α levels whereas unfavorable parameters such as relapse (26.0±9.4 vs. 29.7±8.2, P=0.107), surgery requirement (22.8±11.1 vs. 29.1±8.1, P=0.147), steroid requirement (25.9±9.0 vs. 28.6±8.9, P=0.595), and anti-TNF intensification (22.3±3.8 vs. 28.5±9.0, P=0.183) were increased in patients with low m-TNF-α levels.
High mucosal TNF-α levels before treatment have favorable effects on anti-TNF treatment response in CD. Presence of high m-TNF-α levels at the diagnosis may be encouraging in early initiation of anti-TNF treatment.
To compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent.
Prospective ...observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months.
103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (P=.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events.
RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario.
Evaluar la eficacia y la seguridad a corto plazo del tratamiento de pacientes con artritis reumatoide (AR) con rituximab (RTX) comparado con un anti-TNF (2TNF) tras retirada de un primer anti-TNF.
Estudio multicéntrico prospectivo, observacional, de práctica clínica de pacientes con AR grave refractaria a anti-TNF que recibieron RTX comparados con los que recibieron un 2TNF. Comparación de las variables de eficacia y respuesta EULAR buena/moderada a los 6 meses.
Ciento tres pacientes incluidos; 82 alcanzan seguimiento a 6 meses, 73,7% mujeres. Datos basales grupo RTX y 2TNF, respectivamente: 8,6 y 6,6 NAD, 8,8 y 7,5 NAI, 5,45 ± 1,28 y 5,18 ± 1,21 en DAS28 (p=0,048), 41 y 38,7mmHg de VSG, y 1,2 y 1,0 en HAQ. Mejoría en todos los parámetros en ambos grupos sin diferencias significativas (excepto mayor reducción de VSG con RTX). Ausencia de efectos adversos graves.
El uso de RTX en segunda línea de terapia biológica tras fallo a un primer anti-TNF en práctica clínica muestra mejoría en las variables de eficacia y funcionalidad a los 6 meses, sin presentar efectos adversos graves. Estos resultados no difieren de los observados tras el uso de un segundo anti-TNF en el mismo escenario clínico.
The role of innate immune response in protection against leptospirosis is poorly understood. We examined the expression of the chemokine CXCL2/MIP-2 and the cytokine TNF-α in experimental resistant ...and susceptible mice models, C3H/HeJ, C3H/HePas and BALB/c strains, using a virulent strain of Leptospira interrogans serovar Copenhageni. Animals were infected intraperitoneally with 107 cells and the development of the disease was followed. Mortality of C3H/HeJ mice was observed whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. The infection was confirmed by the presence of leptospiral DNA in the organs of the animals, demonstrated by PCR. Sections of the organs were analyzed, after H&E stain. The relative expression of mRNA of chemokine CXCL2/MIP-2 and cytokine TNF-α was measured in lung, kidney and liver of the mice by qPCR. The concentrations of these proteins were measured in extracts of tissues and in serum of the animals, by ELISA. Increasing levels of transcripts and protein CXCL2/MIP-2 were detected since the first day of infection. The highest expression was observed at third day of infection in kidney, liver and lung of BALB/c mice. In C3H/HeJ the expression of CXCL2/MIP-2 was delayed, showing highest protein concentration in lung and kidney at the 5th day. Increasing in TNF-α transcripts were detected after infection, in kidney and liver of animals from the three mice strains. The expression of TNF-α protein in C3H/HeJ was also delayed, being detected in kidney and lung. Our data demonstrated that Leptospira infection stimulates early expression of CXCL2/MIP-2 and TNF-α in the resistant strain of mice. Histological analysis suggests that the expression of those molecules may be related to the influx of distinct immune cells and plays a role in the naturally acquired protective immunity.
► Innate immune response in leptospirosis in susceptible or resistant mice strains. ► Expression of TNF-a and CXCL2/MIP-2 occurs in early stages of Leptospira infection. ► The expression of the cytokines is dependent on the organ and time after infection. ► Control of bacterial load correlates with integrity of the innate immune system. ► Susceptible mice C3H/HeJ (TLR4-) present more tissue damage than parental strain.
La incidencia de infección crónica por el virus de hepatitis C (VHC) en un paciente con enfermedad reumática es un desafío diagnóstico y terapéutico, ya que los medicamentos utilizados en el ...tratamiento de la artritis reumatoide (AR) y del lupus eritematoso sistémico (LES) son hepatotóxicos. Describimos el caso de una paciente de sexo femenino, con superposición de AR y LES con serología positiva para hepatitis C, quien recibió tratamiento con interferón alfa sin respuesta y en presencia de actividad de la enfermedad reumática fue refractaria al tratamiento, siendo utilizado Anti-TNF etanercept con resolución de la sintomatología.
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