Eficacia y seguridad de la terapia combinada con fármacos modificadores de la enfermedad sintéticos en la artritis reumatoide: revisión sistemática de la literatura / Efficacy and safety of combined therapy with synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: systematic literature review

OBJETIVO: 1) Revisar sistemática y críticamente la evidencia sobre eficacia y seguridad de la terapia combinada con fármacos modificadores de la enfermedad (FAME) sintéticos en la artritis reumatoide (AR); 2) Emitir recomendaciones prácticas sobre su uso. MÉTODOS: Se realizó una revisión sistemática de la literatura con una estrategia de búsqueda bibliográfica sensible en Medline, Embase y Cochrane Library. Se seleccionaron ensayos clínicos aleatorizados que analizasen la eficacia y/o seguridad de 1) la terapia combinada con FAME sintéticos comparada con la terapia secuencial con FAME sintético en la AR de inicio; y 2) la combinación metotrexato+leflunomida o la triple terapia de FAME sintéticos en la AR establecida refractaria a FAME sintéticos. Dos revisores realizaron la primera selección por título y abstract y 11 la selección tras lectura en detalle y la recogida de datos. La calidad se evaluó con la escala de Jadad. En una reunión de grupo nominal en base sus resultados se consensuaron una serie de recomendaciones. RESULTADOS: Finalmente no se incluyó ningún artículo en la RSL. Del análisis de los artículos revisados se encontró la eficacia en las AR de inicio del tratamiento precoz con FAME sintéticos siguiendo una estrategia «treat to target» y en AR establecidas refractarias a FAME sintéticos la de la terapia combinada con FAME sintéticos. Con ello se generaron 5 recomendaciones sobre la terapia combinada con FAME sintéticos. CONCLUSIONES: Estas recomendaciones pretenden facilitar la toma de decisiones con el uso de la terapia combinada con FAME sintéticos en la AR

OBJECTIVE: 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use. METHODS: A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. RESULTS: Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a "treat to target" strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. CONCLUSIONS: These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA

Efficacy and Safety of Combined Therapy With Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Systematic Literature Review. / Eficacia y seguridad de la terapia combinada con fármacos modificadores de la enfermedad sintéticos en la artritis reumatoide: revisión sistemática de la literatura.

OBJECTIVE: 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use. METHODS: A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. RESULTS: Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a "treat to target" strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. CONCLUSIONS: These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.

Clinical and immunogenetic factors associated with pneumonia in patients with systemic lupus erythematosus: a case-control study.

OBJECTIVE: To determine the incidence of pneumonia and associated factors in a single-center systemic lupus erythematosus (SLE) cohort. METHODS: We included all our SLE patients [1997 American College of Rheumatology (ACR) criteria] with ≥ 1 pneumonia event, and 196 age and sex-matched SLE controls with no pneumonia events. Cumulative clinical data, weighted Systemic Lupus International Collaborating Clinics/ACR damage index (wSLICC/ACR-DI), comorbidities, and risk factors for pneumonia were retrospectively collected. The standardized incidence ratio (SIR) of pneumonia was estimated. Polymorphisms at genes coding for mannose binding lectin (MBL), MBL-associated serine protease 2, Fc-gamma receptors, and surfactant proteins A1, A2, and D were determined, and their potential association with pneumonia was analyzed. Patients with and without pneumonia were compared using a multivariate logistic regression model for adjustment of pneumonia-associated factors. RESULTS: Thirty-six of 232 patients with SLE had experienced ≥ 1 pneumonia event. SIR for pneumonia was 5.1 (95% CI 3.5-7.4; p < 0.0001). Excluding patients receiving immunosuppressive therapy at the time of pneumonia (13%), associations were found for Katz Severity Index (KSI) (p = 0.016), wSLICC/ACR-DI (p = 0.044), number of SLE criteria (p = 0.005), hospital admissions (p < 0.001), FCGR2A HH genotype (p = 0.03), previous use of immunosuppressive therapy (p = 0.049), cutaneous ulcers (p < 0.001), and vasculitis (p = 0.008) in bivariate analyses. In the multivariate analysis adjusted to previous immunosuppressive treatment, only KSI and FCGR2A HH genotype remained statistically significant (p = 0.05 and p = 0.03, respectively). CONCLUSION: The incidence of pneumonia in patients with SLE is higher than that in the general population, and particularly high in severe SLE, regardless of immunosuppressive therapy. The HH genetic variant of FCGR2A appears to predispose patients with SLE to pneumonia.