Methotrexate: an old new drug in autoimmune disease

Abstract

Methotrexate (MTX) is currently considered, among disease-modifying anti-rheumatic drugs (DMARDs), the ‘anchor-drug’ in the treatment of rheumatoid arthritis. In the last 25 years, there has been a marked expansion in the use of MTX in different inflammatory diseases. Its low cost, associated to a good long-term efficacy and safety profile, justifies the use of MTX as a first-line disease-modifying drug or alternatively, a steroid-sparing medication in this field of medicine. Although new emerging options, including biological treatments, are being established in the therapeutic scenario, the good cost/benefit ratio of MTX supports the choice of this drug in combination with these newer therapies, enhancing the efficacy of these combination therapies and decreasing the risk of potential side effects.

Keywords::

• ankylosing spondylitis
• granulomatosis with polyangiitis (Wegener’s)
• inflammatory bowel diseases
• mechanism of action
• methotrexate
• psoriasis
• rheumatoid arthritis
• side effects
• systemic lupus erythematosus
• systemic sclerosis

Acknowledgements

The authors thank F Sensini for her technical assistance.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Methotrexate (MTX) is currently considered, among disease-modifying anti-rheumatic drugs (DMARDs), the ‘anchor drug’ in the treatment of rheumatoid arthritis (RA).

• In the last 25 years, there has been a marked expansion in the use of MTX in different inflammatory diseases. Its low cost associated with a good long-term efficacy and safety profile, justifies the use of MTX as a first-line disease-modifying drug or alternatively, a steroid-sparing medication in this field of medicine.

• Many immunosuppressive effects, mainly observed during RA treatment, suggested the possible administration of MTX in different conditions and may contribute to the effectiveness of the drug in different autoimmune diseases.

• MTX is used to treat moderate-to-severe psoriasis.

• Although no serious side effects were reported in clinical trials, at present, there is no evidence to support any benefit in the treatment of ankylosing spondylitis with MTX.

• In systemic sclerosis, MTX has be used for different clinical features such as skin involvement, arthritis and myositis

• In clinical trials, MTX was well tolerated demonstrating a good safety profile in systemic lupus erythematosus patients, and although further studies need to better evaluate the role of MTX, this drug may be a suitable therapeutic option in management of these patients.

• MTX has been found to be as effective as cyclophosphamide in inducing remission in antineutrophil cytoplasmic antibody-associated vasculitis patients who have active but not severe disease.

• A Cochrane meta-analysis of randomized controlled trials focused to assess the possibility that MTX may induce remission in corticosteroid-dependent Crohn’s disease and showed that MTX was superior to placebo.

Notes