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Three decades of low-dose methotrexate in rheumatoid arthritis: Can we predict toxicity?

  • PATHOGENESIS AND THERAPY IN AUTOIMMUNE DISEASES
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Abstract

Methotrexate (MTX) is the anchor disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA) treatment. It is used in monotherapy and/or in combination with other synthetic or biological DMARDs, and is known to have the best cost-effectiveness and efficacy/toxicity ratios. However, toxicity is still a concern, with a significant proportion of patients interrupting long-term treatment due to the occurrence of MTX-related adverse drug reactions (ADRs), which are the main cause of drug withdrawal. Despite the extensive accumulated experience in the last three decades, it is still impossible in routine clinical practice to identify patients prone to develop MTX toxicity. While clinical and biological variables, including folate supplementation, partially help to minimize MTX-related ADRs, the advent of pharmacogenomics could provide further insight into risk stratification and help to optimize drug monitoring and long-term retention. In this paper, we aimed to review and summarize current data on low-dose MTX-associated toxicity, its prevention and predictors, keeping in mind practical RA clinical care.

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Authors and Affiliations

  1. Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon Academic Medical Centre, Edifício Egas Moniz, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal

    Vasco C. Romão, Helena Canhão & João Eurico Fonseca

  2. Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Centre, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal

    Vasco C. Romão, Helena Canhão & João Eurico Fonseca

  3. Department of Pharmaceutical Sciences, CESPU Institute of Research and Advanced Training in Health Sciences and Technologies, Higher Institute of Health Sciences (ISCS-N), Rua Central de Gandra 1317, 4585-116, Gandra PRD, Portugal

    Aurea Lima

  4. Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    Aurea Lima

  5. Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal

    Aurea Lima

  6. Faculty of Medicine of University of Porto (FMUP), Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Miguel Bernardes

  7. Rheumatology Department, São João Hospital Centre, Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Miguel Bernardes

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  1. Vasco C. Romão
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  2. Aurea Lima
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  3. Miguel Bernardes
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Correspondence to João Eurico Fonseca.

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Vasco C. Romão and Aurea Lima have contributed equally to this work.

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Romão, V.C., Lima, A., Bernardes, M. et al. Three decades of low-dose methotrexate in rheumatoid arthritis: Can we predict toxicity?. Immunol Res 60, 289–310 (2014). https://doi.org/10.1007/s12026-014-8564-6

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