Tumour necrosis factor inhibitors

The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of many chronic inflammatory and rheumatic diseases, in particular, Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Controlled trials have shown that the TNF inhibitors (etanercept, infliximab and adalimumab) significantly reduce symptoms and signs, improve function and quality of life, and reduce radiologically evident damage in patients with rheumatoid diseases. For reasons that are not entirely clear, etanercept does not work in Crohn's disease. Injection site and intravenous reactions and increased risk of infection (in particular, reactivation of tuberculosis) are associated with the use of these agents. Increased risk of lymphoproliferative disease, the development of lupus-like syndromes and demyelination, including optic neuritis and reactivation of multiple sclerosis, are under evaluation in long-term follow-up studies. The TNF inhibitors are expensive (about $18000 per year), and in some patients need to be given continuously to maintain benefit, even in the presence of other immunosuppressive therapy.

A rheumatoid arthritis gyógyszeres terápiája; a nemzetközi és a hazai szakirodalom szisztematikus áttekintése

Az új DMARD-ok: leflunomide, etanercept és infliximab terápia a tudományos bizonyítékok szisztematikus áttekintése; az RA prevalenciája és az egészségügyi igénybevételi mutatók Magyarországon

Systematic review and analysis of evidences on clinical efficacy and cost-effectiveness of biological drugs for the treatment of Ankylosing Spondylitis

Technology: Infliximab and comparator biological such as adalimumab, etanercept, golimumab. Conditions: Ankylosing spondylitis (AS) Issue: Infliximab is registered to be used in patients with AS. The aim of the Report is to evaluate the clinical efficacy and safety of infliximab and comparator biologicals for the treatment of adult AS. Methods: Systematic literature review and analysis as well as meta-analysis (direct and indirect comparison) of published randomised controlled clinical trials (RCT) were performed, all relevant health economics literature were identified ad analysed. Results: Clinical efficacy of biological therapies is based on good clinical evidences regarding to all clinical efficacy endpoints (ASAS20, ASAS40, ASAS 5/6, and BASDAI 50% response). Altogether, 22 trials are included in our meta-analysis, 12 infliximab, 3 adalimumab studies, 6 etanercept and 1 golimumab. Efficacy of biological treatments for the treatment of AS has been established by clinical scientific evidences, significant improvement at all outcomes considered was confirmed. According to the results of indirect comparison, there were no significant difference between biological treatments and placebo in terms of safety and tolerability endpoints. We found no significant difference between the clinical efficacy and safety of infliximab, adalimumab, etanercept and golimumab therapies. Cost-utility analysis of adalimumab and/or infliximab, etanercept and golimumab treatment for AS were performed in the UK, Canada, The Netherlands, Germany, Spain and France. There are no cost-utility studies from Eastern Central Europe. Implications for decision making: Efficacy of infliximab and comparator biologicals for the treatment of Ankylosing Spondylitis (AS) was proved by clinical evidence, significant improvement at all outcomes considered was confirmed. We found no significant differences in efficacy and safety of different biological treatments. Health economics results suggest that biological therapies are cost-effective alternatives for the treatment of AS in group of developed high income countries. There is a lack of health economics results in Central-Eastern European countries however these data are more and more required by governments and funders as part of the company economic dossiers.

Niveles de biológicos: eficacia e inmunogenicidad del tratamiento para enfermedad inflamatoria intestinal

Programa de doctorado: Avances en Medicina Interna. La fecha de publicación es la fecha de lectura

An anti-TNF--α antibody mimetic to treat ocular inflammation

Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice model after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

Capsule endoscopy in inflammatory bowel disease type unclassified and indeterminate colitis serologically negative

BACKGROUND: The value of capsule endoscopy in the setting of inflammatory bowel disease type unclassified (IBDU) and indeterminate colitis (IC) remains obscure. The aim was to evaluate the clinical impact of capsule endoscopy on IBDU/IC patients with negative serology. METHODS: Eighteen patients with long-standing IBDU (n = 14) and IC (n = 4) were enrolled to undergo a capsule endoscopy and then followed prospectively. Lesions considered diagnostic of Crohn's disease (CD) were 4 or more erosions/ulcers and/or a stricture. The median follow-up time after capsule endoscopy was 32 ± 11 months (23-54 months). RESULTS: Total enteroscopy was possible in all patients. In 2 patients the examination was normal (Group 1). In 9 patients subtle findings were observed (Group 2): focal villi denudation (n = 1) and fewer than 4 erosions/ulcers (n = 8). In 7 patients, 4 or more erosions/ulcers were detected (Group 3), leading to a diagnosis of CD. However, their treatment was not reassessed on the basis of the capsule findings. Until now, a definitive diagnosis has been achieved in 2 additional patients: 1 from Group 1 (ulcerative colitis) and another patient from Group 2 (CD), who began infliximab infusions. Nine patients remained indeterminate at follow-up. CONCLUSIONS: Although capsule endoscopy enabled the diagnosis of CD in 7 patients, in none of them was the clinical management changed. Moreover, a change in therapy due to a diagnosis of CD was made for only 1 patient, who presented nonspecific findings. Our results suggest that capsule findings are not helpful in the work-up of these patients

Doença de Behçet: a nossa realidade

Introdução: A doença de Behçet é uma vasculite inflamatória sistémica, de etiologia desconhecida, caraterizada por episódios de recidiva de úlceras orais e genitais, lesões oculares e cutâneas, podendo atingir virtualmente todos os sistemas. As manifestações oculares são comuns e com consequências visuais importantes. O objectivo deste trabalho foi analisar os parâmetros demográficos, manifestações clinicas, terapêutica e principais complicações em doentes com doença de Behçet ocular. Métodos: Estudo descritivo e retrospetivo, que incluiu 11 doentes com o diagnóstico de doença de Behçet, segundo os critérios do ISG, observados na consulta de Inflamação Ocular do Hospital Prof. Doutor Fernando da Fonseca nos últimos 3 anos. Resultados: Identificaram-se 11 doentes, 5 homens e 6 mulheres, todos caucasianos. A idade média ao diagnóstico foi de 33,45±6,49 anos. A manifestação ocular foi o primeiro sinal da doença em 2 doentes. Em 72,7% dos casos as manifestações oculares foram bilaterais. Identificaram-se 4 casos de panuveíte, 3 de uveíte posterior, 2 de uveíte anterior, 1 de queratite e 1 caso de episclerite. O glaucoma e a catarata foram a complicação ocular mais frequente. O tratamento sistémico incluiu a corticoterapia oral em associação com terapêutica adjuvante imunossupressora, sendo os mais utilizados a azatioprina e a ciclosporina. Em 3 doentes houve necessidade de terapêutica biológica com infliximab para controlo da doença. Conclusão: A manifestação ocular mais frequente foi a panuveite. Esta doença pode condicionar complicações oculares com diminuição irreversível da acuidade visual. A orientação destes doentes exige uma abordagem global e inter-disciplinar.

Bilateral Panuveitis at Etanercept Initiation for Juvenile Idiopathic Arthritis

Introduction: Uveitis is a well-known extra-rheumatological manifestation of juvenile idiopathic arthritis (JIA). Tumor necrosis factor has been used to treat uveitis associated with inflammatory diseases. A new onset uveitis under anti-TNF therapy is uncommon. Case presentation: A 12-years-old male, affected since the age of six years, by a severe form of polyarticular JIA. When etanercept was started, he presented panuveitis bilaterally, so we switched to infliximab with good response. Conclusions: The TNF soluble receptor could be considered as a possible promoter in inducing endogenous new onset uveitis in JIA.

Seguridad del paciente tratado con E.I.M.I en una UCCYU: aplicación de NANDA-NOC-NIC

El infliximab o remicade® es un anticuerpo monoclonal quimérico, utilizado para disminuir la cascada inflamatoria en enfermedades inflamatorias. Los objetivos de esta investigación es normalizar la práctica clínica de los pacientes tratados con Infliximab, disminuir la variabilidad de cuidados y mejorar la seguridad de estos pacientes. Se ha elaborado un registro de diagnósticos de enfermería, NOC y NIC que con mayor incidencia se presentan en pacientes con E.I.M.I tratados con Inflixibab, con los cuales se pueden realizar cuidados de enfermería de calidad, logrando garantizar el registro y transmisión adecuada de información relativa a los cuidados.

Kawasaki Disease and Peripheral Gangrene in Infancy

Introduction: Early diagnosis and treatment of Kawasaki disease as the most common cause of acquired heart disease in childhood, may significantly improve the prognosis. Diagnosing infantile Kawasaki (younger than a year) is difficult because of obscure symptoms; at the same time they are at the higher risk of coronary abnormalities. Case Presentation: We report three infants with prolonged (more than 5 days) fever and peripheral gangrene without any other clinical manifestations of Kawasaki disease. Kawasaki was diagnosed due to dilation of coronary artery and other aortic branches, thrombocytosis, and rising of ESR and CRP. All patients were treated with high dose aspirin, IVIG and pulse therapy with methylprednisolone. Additionally, cytotoxic drugs or infliximab were used for two of them because of severe aneurysms in the aortic branches. All 3 patients received aspirin with anti-platelet aggregation dose and 2 patients heparin as an anti-coagulant agent for longtime. After adequate treatment, peripheral gangrene, arterial dilations and aneurysms improved, but during 12 months follow-up coronary aneurysms did not improve completely. Conclusions: Peripheral gangrene must be regarded as an important sign of infantile Kawasaki disease early treatment of which can prevent severe permanent coronary involvements and sequels.

Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis

OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

Revisión del uso de los medicamentos biosimilares vs. biológicos: implicaciones para la salud en Colombia.

Este documento tiene como objetivo describir las implicaciones para la salud con el uso de medicamentos biosimilares en comparación con los medicamentos biológicos en Colombia. Así mismo, describir el contexto normativo acerca del uso de medicamentos biosimilares, las recomendaciones y lineamientos sobre seguridad y efectividad del uso de medicamentos Biosimilares y Biológicos, partiendo de sus diferencias biomoleculares. Para esto, se desarrolló una revisión documental electrónica y manual de la literatura en bases de datos, revistas y libros limitada a términos MeSH. La selección de los artículos incluyo documentos completos publicados en revistas indexadas de los últimos 10 años, en español e inglés; la información recolectada se organizó para la construcción del presente documento. Concluyendo, se encontró que las patentes de muchos medicamentos biológicos han vencido o están próximas a caducar y varios biosimilares están desarrollándose y comercializándose incluso en países sin regulaciones estrictas. Los biosimilares nunca podrán ser iguales al original por su complejidad molecular, por ello debemos integrarlos a los sistemas de farmacovigilancia mejorando trazabilidad e identificando su origen mientras se establecen denominaciones comunes distinguibles. La evidencia actual sugiere que la regulación de medicamentos biosimilares debe ser evaluada y armonizada en todo el mundo.

Factores asociados a respuesta de abatacept subcutaneo en artritis reumatoide

INTRODUCCION Dado que la artritis reumatoide es la artropatía inflamatoria más frecuente en el mundo, siendo altamente discapacitante y causando gran impacto de alto costo, se busca ofrecer al paciente opciones terapéuticas y calidad de vida a través del establecimiento de un tratamiento oportuno y eficaz, teniendo presentes aquellos predictores de respuesta previo a instaurar determinada terapia. Existen pocos estudios que permitan establecer aquellos factores de adecuada respuesta para inicio de terapia biológica con abatacept, por lo cual en este estudio se busca determinar cuáles son esos posibles factores. METODOLOGIA Estudio analítico de tipo corte transversal de 94 pacientes con diagnóstico de AR, evaluados para determinar las posibles variables que influyen en la respuesta a terapia biológica con abatacept. Se incluyeron 67 de los 94 pacientes al modelo de regresión logística, que son aquellos pacientes en que fue posible medir la respuesta al tratamiento (respuesta EULAR) a través de la determinación del DAS 28 y así discriminar en dos grupos de comparación (respuesta y no respuesta). DISCUSION DE RESULTADOS La presencia de alta actividad de la enfermedad al inicio de la terapia biológica, aumenta la probabilidad de respuesta al tratamiento respecto al grupo con baja/moderada actividad de la enfermedad; OR 4,19 - IC 95%(1,18 – 14.9), (p 0,027). La ausencia de erosiones óseas aumenta la probabilidad de presentar adecuada respuesta a la terapia biológica respecto aquellos con erosiones, con un OR 3,1 (1,01-9,55), (p 0,048). Niveles de VSG y presencia de manifestaciones extra-articulares son otros datos de interés encontrados en el análisis bivariado. Respecto a las variables o características como predictores de respuesta al tratamiento con abatacept, se encuentran estudios que corroboran los hallazgos de este estudio, respecto al alto puntaje del DAS 28 al inicio de la terapia (9, 12). CONCLUSIONES Existen distintas variables que determinan la respuesta a los diferentes biológicos para manejo de AR. Es imprescindible evaluar dichos factores de manera individual con el fin de lograr de manera efectiva el control de la enfermedad y así mejorar la calidad de vida del individuo (medicina personalizada). Existen variables tales como la alta actividad de la enfermedad y la ausencia de erosiones como predictores de respuesta en la terapia con abatacept.