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Vol. 18. Issue 4.
Pages 207-226 (April 2022)
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Vol. 18. Issue 4.
Pages 207-226 (April 2022)
Original Article
Use of parenteral methotrexate in rheumatic diseases: A systematic review
Revisión sistemática del uso de metotrexato por vía parenteral en enfermedades reumáticas
Teresa Otóna,
Corresponding author

Corresponding author.
, Loreto Carmonaa, Estíbaliz Lozaa, María Piedad Rosariob, Jose Luis Andreuc
a Instituto de Salud Musculoesquelética (InMusc), Madrid, Spain
b AETSA, Evaluación de Tecnologías Sanitarias de Andalucía, Fundación Pública Andaluza Progreso y Salud, Spain
c Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
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Tables (2)
Table 1. Table of evidence.
Table 2. Efficacy.
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To analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases.


A systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies.


Out of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data.


Parenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.

Systematic review

Analizar la eficacia, adherencia, satisfacción del paciente, seguridad, farmacodinámica y costo-efectividad del (MTX) parenteral en pacientes con enfermedades reumáticas.


Se llevó a cabo una revisión sistemática basada en una estrategia de búsqueda en Medline, Embase y Cochrane Library (inicio-06/2019). Se identificaron estudios que incluyeran pacientes adultos con enfermedades reumáticas en tratamiento con MTX parenteral y que analizaran datos de eficacia, adherencia, satisfacción, seguridad, farmacocinética o costo-efectividad. En cuanto a los diseños se permitieron revisiones sistemáticas, ensayos clínicos o estudios observacionales, incluyendo transversales y estudios con muestras pequeñas si eran estudios de farmacocinética.


De 4.160 artículos identificados, se incluyeron finalmente 80. El MTX parenteral parece útil de manera general y en especial en aquellos pacientes con respuesta insuficiente a MTX oral. La vía parenteral no parece aumentar la tasa ni la gravedad de los eventos adversos con respecto a la oral y podría reducir costes en aquellos pacientes con respuesta inadecuada a MTX oral. La adherencia y satisfacción se ven favorecidos por programas de entrenamiento en la vía parenteral. Los resultados en enfermedades reumáticas distintas a la artritis reumatoide (AR), son muy escasos y no permiten obtener datos concluyentes.


El MTX por vía parenteral podría ser una alternativa al uso de MTX oral, por su perfil de eficacia, seguridad, adherencia, satisfacción y resultados fármaco-económicos, especialmente en pacientes con AR.

Palabras clave:
Revisión sistemática


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