OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
OBJETIVO: Desarrollar una nueva pauta de tratamiento farmacológico basado en la evidencia para la artritis reumatoide (AR).
MÉTODOS: Se realizó una revisión sistemática para sintetizar la evidencia de los beneficios y los daños de diferentes opciones de tratamiento. Se utilizó la clasificación de las recomendaciones de la evaluación, la metodología de Evaluación (GRADE) Desarrollo y en evaluar la calidad de las pruebas. Empleamos un proceso de consenso del grupo para clasificar la fuerza de las recomendaciones (ya sean fuertes o condicionales). Una recomendación sólida indica que los médicos están seguros de que los beneficios de una intervención son muy superiores a los daños (o viceversa). Una recomendación condicional denota incertidumbre sobre el equilibrio entre los beneficios y los daños y / o una mayor variabilidad significativa en los valores y las preferencias del paciente.
RESULTADOS: La guía cubre el uso de los fármacos tradicionales modificadores de la enfermedad (DMARD) antirreumáticos, agentes biológicos, tofacitinib, y los glucocorticoides en los primeros 6 meses (<) y estableció (6 meses o más) RA. Además, proporciona recomendaciones sobre el uso de un enfoque de tratar al objetivo, se estrecha y descontinuar medicamentos y el uso de agentes biológicos y FAME en pacientes con hepatitis, insuficiencia cardíaca congestiva, enfermedad maligna, y las infecciones graves. La directriz se refiere a la utilización de las vacunas en pacientes que inician / recepción de FARME o agentes biológicos, la detección de la tuberculosis en pacientes que inician / recepción de agentes biológicos o tofacitinib, y la vigilancia de laboratorio para los DMARD tradicionales. La guía incluye 74 recomendaciones: 23% son fuertes y el 77% son condicionales.
CONCLUSIÓN: Esta directriz RA debe servir como una herramienta para los médicos y pacientes (nuestros dos audiencias objetivo) para las decisiones de tratamiento farmacológico en situaciones clínicas más frecuentes. Estas recomendaciones no son prescriptivos, y las decisiones de tratamiento deben ser tomadas por los médicos y los pacientes a través de un proceso de toma de decisiones compartida, teniendo en cuenta los valores de los pacientes, las preferencias y las comorbilidades. Estas recomendaciones no deben ser utilizados para limitar o no permitir el acceso a las terapias.
To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS:
PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS:
Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS:
This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
