OBJECTIVE: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA.
METHODS: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy).
RESULTS: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events.
CONCLUSION: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents.
OBJETIVOS: Este estudio se realizó para determinar si subcutánea (SC) de metotrexato (MTX) hace un mejor rendimiento en la biodisponibilidad, eficacia clínica, los efectos secundarios ocurrencia, y el fracaso del tratamiento en el tratamiento de la AR en comparación con MTX oral.
MÉTODOS: Las bases de datos PubMed, Web of Science, Embase y Cochrane Library se realizaron búsquedas sistemáticas. Siete estudios con 1335 pacientes fueron elegibles para la extracción de datos y meta-análisis. Los resultados del meta-análisis se presentaron como diferencia de medias (DM) o ración impar (OR) con un intervalo de confianza del 95% (IC del 95%).
RESULTADOS: Meta-análisis mostraron que el MTX SC puede aumentar significativamente el AUC 0-t (área bajo la curva de concentración plasmática de la administración a durar concentración observada en el tiempo t) (MD = 506,84; IC del 95%: 80,80 a 932,89), acortar el tiempo de alcanzar la concentración máxima observada (Tmáx) (MD = -0.13; IC del 95%: -0,25 a la -0.01) y la eliminación terminal aparente vida media (t (1/2)) (MD = -0,39; IC del 95%: - IC del 95%; 0,70 a -0,08), reducir la incidencia de náuseas (OR = 0,53: 0,28 a 0,97) y diarrea (OR = 0,43; IC del 95%: 0,20 a 0,95), mejorar la American College of Rheumatology criterios para el 20% mejoría (ACR20) (OR = 1,68; IC del 95%: 1,09 a 2,61) y ACR70 (OR = 1,52; IC del 95%: 1.2 a 2.26), y aliviar el dolor (MD = -0,65; IC del 95%: -0,93 a -0,37) en comparación con MTX oral. Sin embargo, las diferencias en la concentración plasmática máxima (Cmáx), la aparición de dolor de cabeza, vómitos y dispepsia, ACR50, el fracaso del tratamiento no fueron significativas entre los dos grupos.
CONCLUSIÓN: vía SC de MTX a dosis altas hizo un mejor rendimiento en la mejora de la biodisponibilidad y la eficacia clínica, la reducción de los trastornos GI, pero no puede disminuir el fracaso del tratamiento en comparación con la administración oral de MTX.
Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA.
METHODS:
PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy).
RESULTS:
The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events.
CONCLUSION:
Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents.
