Terapia combinada en enfermedad inflamatoria intestinal: ¿una asociación necesaria? / Combination therapy in inflammatory bowel disease: a necessary association?

The management of inflammatory bowel disease (IBD) is constantly changing due to the arrival of new therapeutic agents. Combined therapy (biological associated with immunosuppressive therapy) has proven to be effective, reducing immunogenicity (antibody formation), optimizing the pharmacokinetics of biological therapy with anti-TNF. This therapeutic strategy has associated risks (neoplasia and intercurrent infections) that are not only explained by the use of drugs but also by the increase of cases in older ages. It is essential for the medical team to be familiar with the optimization and personalization of the therapy to achieve clear therapeutic objectives with the lowest possible risks.

El manejo de la enfermedad inflamatoria intestinal (EII) está en constante cambio, debido a la llegada de nuevos agentes terapéuticos. La terapia combinada (terapia biológica asociada a inmunosupresores) ha demostrado ser efectiva al disminuir la inmunogenicidad (formación de anticuerpos) permitiendo la optimización farmacocinética. Esta estrategia terapéutica tiene riesgos asociados (neoplasias e infecciones intercurrentes) que no sólo se explican por el uso de fármacos sino también por el aumento de casos en edades más avanzadas. Es fundamental que el equipo tratante este familiarizado con la optimización y personalización de la terapia para así lograr objetivos terapéuticos claros con los menores riesgos posibles.

Expression of lymphatic markers and lymphatic growth factors in psoriasis before and after anti-TNF treatment

BACKGROUND: Angiogenesis is an early stage of psoriatic lesion development, but less is known about lymphagiogenesis and its role in the development of psoriasis. OBJECTIVE: To examine the expression of specific lymphatic markers and lymphatic growth factors in untreated psoriatic skin, in the unaffected skin of patients and skin of healthy volunteers, as well as their alteration after treatment with an anti-TNF agent. METHODS: Immunohistochemistry for the lymphatic markers D2-40 and LYVE-1, in addition to the VEGF-C and VEGF-D growth factors, was performed in the skin biopsies of psoriatic lesions and adjacent non-psoriatic skin of 19 patients before and after treatment with etanercept, as well as in the skin biopsies of 10 healthy volunteers. RESULTS: The expressions of D2-40, VEGF-C and VEGF-D on lymphatic vessels underwent statistically significant increases in untreated psoriatic skin compared with non-lesional skin, in contrast to LYVE-1, which did not involve significant increase in expression in psoriatic skin. VEGF-C expression on lymphatic vessels diminished after treatment with etanercept. Moreover VEGF-C and VEGF-D staining on fibroblasts presented with higher expression in lesional skin than in non-lesional adjacent skin. CONCLUSION: Remodeling of lymphatic vessels possibly occurs during psoriatic lesion development, parallel to blood vessel formation. The exact role of this alteration is not yet clear and more studies are necessary to confirm these results. .

Drug Survival Rates of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

We investigated the compliance of Korean patients using tumor necrosis factor (TNF) inhibitors to treat rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and identified potential predictors associated with treatment discontinuation. The study population comprised 114 RA and 310 AS patients treated with TNF inhibitors at a single tertiary center for at least 1 yr from December 2002 to November 2011. Of the 114 RA patients, 64 (56.1%) discontinued their first TNF inhibitors with a mean duration of 18.1 months. By contrast, 65 of 310 patients (21.0%) with AS discontinued their first TNF inhibitors, with a mean duration of 84 months. Although the survival rate did not differ among the three TNF inhibitors in the AS patients, the etanercept group had a lower discontinuation rate than the infliximab group in the RA patients. In addition, RA patients who received corticosteroids in combination with TNF inhibitors were more likely to discontinue their TNF inhibitors. The independent predictors of drug discontinuation in AS patients were male gender and complete ankylosis on radiographs of the sacroiliac joint. Our results provide further evidence that real-life treatment outcomes of RA and AS patients may be different from those observed in randomized clinical trials.

Drug Survival Rates of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

We investigated the compliance of Korean patients using tumor necrosis factor (TNF) inhibitors to treat rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and identified potential predictors associated with treatment discontinuation. The study population comprised 114 RA and 310 AS patients treated with TNF inhibitors at a single tertiary center for at least 1 yr from December 2002 to November 2011. Of the 114 RA patients, 64 (56.1%) discontinued their first TNF inhibitors with a mean duration of 18.1 months. By contrast, 65 of 310 patients (21.0%) with AS discontinued their first TNF inhibitors, with a mean duration of 84 months. Although the survival rate did not differ among the three TNF inhibitors in the AS patients, the etanercept group had a lower discontinuation rate than the infliximab group in the RA patients. In addition, RA patients who received corticosteroids in combination with TNF inhibitors were more likely to discontinue their TNF inhibitors. The independent predictors of drug discontinuation in AS patients were male gender and complete ankylosis on radiographs of the sacroiliac joint. Our results provide further evidence that real-life treatment outcomes of RA and AS patients may be different from those observed in randomized clinical trials.

Aplicación práctica del uso de la terapia anti-TNF en la enfermedad de Crohn: ¿Cuándo comenzar, cuál elegir, cómo predecir la respuesta, cuándo cambiar y cuándo suspender? / Practical application of anti-TNF therapy for luminal Crohn`s disease: when to start, which drug to choose, how to predict response,when to change and when to stop?

Anti-tumor necrosis factor (anti-TNF) therapy has been an important step in the management of inflammatory bowel disease. These drugs proved to reduce the need for both hospitalization and surgery in Crohn`s disease patients. In consideration of high economic cost and safety issues there is the need to have clear recommendations for their use. Better patient selection might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease, whilst also minimizing the complications associated with therapy. All biological drugs are potentially immunogenic and this can be reduced by combination with immunomodulators. However, the balance of risk and benefit of this strategy must be judged for individual patients. Further, the measurement of levels and anti-drug antibodies for these drugs may help to optimize therapy and to avoid loss of response. Finally, in some patients an appropriate strategy for stopping biological treatment is possible.

La terapia biológica anti-factor de necrosis tumoral (anti-TNF) ha sido un importante avance en el manejo de las enfermedades inflamatorias intestinales. Estos fármacos han demostrado reducir la necesidad de hospitalización y cirugía en pacientes con Enfermedad de Crohn. En consideración a su alto costo económico y su seguridad, es necesario tener claro las recomendaciones sobre su uso. Una mejor selección de los pacientes puede maximizar el beneficio clínico de aquéllos que requieren una terapia más efectiva, para evitar la evolución hacia una enfermedad más discapacitante, mientras minimizamos las complicaciones asociadas a esta terapia. Todos los fármacos biológicos son potencialmente inmunogénicos y esto puede ser reducido con la combinación con inmunomoduladores. Sin embargo, el balance entre los riesgos y beneficios de esta estrategia debe ser evaluado para cada paciente en particular. Por otra parte, la medición de los niveles y los anticuerpos para estos fármacos puede ayudar a optimizar la terapia, evitando la pérdida de respuesta. Finalmente, una apropiada estrategia de suspensión de la terapia biológica es posible en algunos pacientes.

Tratamiento de la artritis reumatoidea con AntiTNF. Experiencia en Uruguay / Treating rheumatoid arthritis with Anti-TNF. Experience in Uruguay

La artritis reumatoidea (AR) es una enfermedad sistémica autoinmune, que se asocia a afectación en la calidad de vida y a un incremento de la morbimortalidad. Los tratamientos remisivos de la AR incluyen fármacos antiartríticos modificadores de le enfermedad (FAME) y terapias con biológicos. En marzo 2010 se incorpora a las prestaciones del Fondo Nacional de Recursos (FNR) el tratamiento con Antifactor de necrosis tumoral (Anti-TNF) se realiza evaluación de la cohorte de pacientes que iniciaron tratamiento antes del 01/05/2011. Objetivos: caracterizar la población y evaluar resultado de la eficacia del tratamiento, según evolución de puntuación de DAS 28. Resultados: se incluyeron 69 pacientes. Las medias de DAs 28 pre y postratamiento evidenciaron una mejoría (p < 0,05). Criterio de mejoría en 76,4% (bajo grado de actividad 37,3% y remisión 14,9%). Efectos adversos en 20 pacientes (en 3 casos motivó suspensión de la terapia). Cambio de droga, principal causa: falla de tratamiento (8/9). Conclusiones: más de 70% obtiene criterio de mejoría por lo cual los resultados en esta primera evaluación de respuesta pueden calificarse como buenos, aunque deberán monitorizarse en el tiempo.

Avaliação do teste T-SPOT-Tb no diagnóstico da infecção tuberculosa latente em pacientes com artrite reumatoide / Evaluation of T-SPOT-TB test in diagnosis of latent tuberculosis infection in rheumatoid arthritis patients

Com a introdução dos Inibidores do Fator de Necrose Tumoral (anti-TNF's) na prática reumatológica, a identificação de casos de infecção tuberculosa latente (ITBL) passou a ser obrigatória antes do início da terapêutica. O teste cutâneo da tuberculina (PPD) não é um teste de screening ideal neste grupo de pacientes, pois apresentam uma resposta inadequada de hipersensibilidade tardia, fundamental para que se produza uma resposta ao antígeno inoculado. Ensaios baseados na detecção da produção de IFN gama in-vitro por células mononucleares periféricas estimuladas por antígenos específicos (ESAT-6 e CFP-10) são mais específicos do que o PPD na detecção de ITBL. O objetivo do nosso estudo foi avaliar o desempenho do T-SPOT.TB no diagnóstico de ITBL em pacientes portadores de artrite reumatóide (AR). Foi realizado um estudo transversal, para avaliação de teste diagnóstico, onde foram incluídos 96 pacientes, divididos em dois grupos - 48 portadores de AR (grupo AR) e 48 pessoas saudáveis, que constituíram o grupo de comparação (grupo COMP). Todos os voluntários foram submetidos a uma entrevista, coleta de sangue para realização do T-SPOT.TB seguida da inoculação da PPD. O T-SPOT.TB foi realizado de acordo com as orientações do fabricante e a leitura do PPD foi realizada após 72 horas da inoculação. Foram calculados a sensibilidade e a especificidade do T-SPOT.TB comparado com o padrão ouro. Uma vez que o PPD é considerado como padrão ouro imperfeito, foram criados quatro modelos para o estudo: PPD isolado; PPD e alterações radiográficas compatíveis com ITBL; PPD e história contato intra-domiciliar e PPD, alterações radiográficas e contato intradomiciliar. A especificidade do T-SPOT.TB variou entre 87 e 90 por cento e o valor preditivo negativo (VPN), entre 94,4 e 100 por cento. A sensibilidade foi 100 por cento nos modelos que não incluíram o RX, caindo para 77,8 e 89,5 por cento nos dois outros. No grupo AR a freqüência de infecção latente diagnosticada pelo PPD foi inferior (14,6 por cento) à encontrada no grupo de comparação (33,3 por cento), com uma diferença estatisticamente significante (p=0,034), o que não ocorreu no grupo COMP. Esta diferença pode ser explicada pelo comprometimento da hipersensibilidade tardia em pacientes com AR. Concluindo, podemos dizer que o T-SPOT.TB apresenta uma especificidade e VPN elevados, sendo capaz de identificar os casos de PPD falso negativos, aumentando a segurança para o uso do anti-TNF.