Seguridad de los fármacos antirreumáticos modificadores de la enfermedad biológicos en la artritis reumatoide Translated title: Safety of biological disease-modifying antirheumatic drugs in rheumatoid arthritis

Abstract

Resumen Objetivo: Analizar la seguridad del tratamiento con fármacos biológicos modificadores de la enfermedad prescritos con mayor frecuencia en pacientes con artritis reumatoide en la práctica clínica habitual. Método: Estudio observacional retrospectivo, a partir de la historia clínica digitalizada de pacientes con artritis reumatoide de un hospital de tercer nivel, sobre la seguridad de los fármacos biológicos modificadores de la enfermedad, entre los años 2001 y 2013. Además de analizar las reacciones adversas que motivaron la retirada del tratamiento, se hizo un análisis de desproporcionalidad comparando los órganos y sistemas implicados en las reacciones adversas asociadas a los diferentes fármacos biológicos modificadores de la enfermedad calculando la odds ratio con un intervalo de confianza del 95% [odds ratio (IC95%)], del periodo de latencia entre el inicio del tratamiento y el diagnóstico de los efectos adversos, y de su conocimiento previo. Resultados: Se analizaron las historias clínicas de 210 pacientes (73% mujeres; mediana de edad: 47 años), que incluían 399 líneas de tratamiento con algún fármaco biológico modificado de la enfermedad y 1.545 reacciones adversas potencialmente relacionadas con ellos. Se identificó un incremento significativo de reacciones adversas en los siguientes órganos y sistemas afectados: trastornos generales y del lugar de administración [2,3 (1,3-4,0)] para infliximab; infecciones [1,6 (1,3‑2,1)] y trastornos del sistema inmunológico [4,2 (1,2-14,6)] para etanercept; trastornos hepatobiliares [2,1 (1,2-3,6)] para adalimumab; trastornos oculares [1,9 (1,2-3,1)] y cardiacos [2,9 (1,0-8,4)] para rituximab; trastornos de la sangre y del sistema linfático [2,9 (1,8-4,7)] para tocilizumab y abatacept [3,0 (1,6-5,8)]. La latencia media osciló entre 5 y 33 meses. La mayor y menor proporción de reacciones adversas conocidas correspondieron a adalimumab (93,6%; p < 0,01) y tocilizumab (55,2%; p < 0,01), respectivamente. Más de la mitad de las retiradas de fármacos biológicos modificadores de la enfermedad asociadas a reacciones adversas se produjeron en el primer año de tratamiento. Conclusiones: Los fármacos biológicos modificadores de la enfermedad inhibidores del factor de necrosis tumoral α se asociaron a la presentación de trastornos generales, infecciones y trastornos del sistema inmunológico y a alteraciones hepatobiliares, mientras que los no inhibidores del factor de necrosis tumoral α se relacionaron con un incremento en los trastornos oculares y cardiacos, trastornos de la sangre y del sistema linfático. La interrupción del tratamiento por reacciones adversas sucedió durante el primer año. La mayoría de las reacciones adversas registradas eran conocidas.

Translated abstract

Abstract Objective: The aim of this study was to assess the safety of the most frequently used biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in clinical practice. Method: A retrospective longitudinal observational study was performed. Clinical information was obtained from the electronic health records of patients diagnosed and treated for rheumatoid arthritis, who had received at least one biologic disease-modifying antirheumatic drug dispensed between 2001 and 2013 from a third-level Hospital pharmacy. Adverse reactions during biologic disease-modifying antirheumatic drugs treatments were analysed, as well as the reasons for treatment discontinuation. A disproportionality analysis (odds ratio with 95% confidence interval) was performed to compare adverse drug reactions related to different system organ classes, the period between the drug start date and the reaction start date (latency period), and previous knowledge of the adverse reactions. Results: In total, 210 patients were included in the analysis (73% women, median age 47 years), with 399 prescriptions for biologic disease-modifying antirheumatic drugs and 1,515 adverse reactions potentially related to them. The increased frequency of adverse reactions for each system organ class related to each biologic disease-modifying antirheumatic drug was as follows: general disorders and administration site disturbances with infliximab (2.3 [1.3-4.0]), infections (1.6 [1.3-2.1]) and immune system reactions with etanercept (4.2 [1.2-14.6]), hepatobiliary disorders with adalimumab (2.1 [1.2-3.6]), ophthalmic adverse reactions (1.9 [1.2-3.1]) and cardiac disorders (2.9 [1.0-8.4]) with rituximab, and blood and lymphatic system disorders with tocilizumab (2.9 [1.8-4.7]) and abatacept (3.0 [1.6-5.8)]. The mean latency period was 5 to 33 months. Most adverse reactions were related to adalimumab (93.6%; P < 0.01), whereas the fewest adverse reactions were related to tocilizumab (55.2%; P < 0.01). Most treatment withdrawals related to adverse reactions were identified during the first year of biologic disease-modifying antirheumatic drugs treatment. Conclusions: Tumour necrosis factor α inhibitors were associated with general disorders and administration site disturbances, infections and immune system reactions, and hepatobiliary abormalities, whereas non-tumour necrosis factor α inhibitors were associated with cardiac disorders as well as blood and lymphatic system disorders. Treatment withdrawals mainly occurred during the first year of treatment. Most of the adverse reactions have been previously described.