Low-dose methotrexate in rheumatic diseases—Efficacy, side effects, and risk factors for side effects

https://doi.org/10.1016/0049-0172(94)90027-2Get rights and content

Abstract

Controlled trials and observational studies have shown low-dose methotrexate (MTX) to be a second-line agent of high potency with a favorable profile of safety and tolerability in the treatment of rheumatoid arthritis (RA). Its riskbenefit ratio in psoriatic arthritis is less well documented. Preliminary reports on its beneficial effects in other disorders, including the systemic manifestations of RA, other spondyloarthritides, and collagen vascular diseases, merit more detailed examination. Gastrointestinal intolerance and hepatic enzyme elevation are the most frequent side effects of MTX; life-threatening events such as severe hemocytopenia and MTX pneumonitis are rare and amenable to prevention by recognizing risk factors and premonitory signs. Hepatotoxicity does not appear to be a major limiting factor in RA patients over the first 2 to 3 years of MTX therapy; its impact on long-term tolerance remains to be clarified.

References (173)

  • P.A. Andersen et al.

    Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study

    Ann Intern Med

    (1985)
  • D.E. Furst et al.

    Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis

    J Rheumatol

    (1989)
  • W.S. Wilke et al.

    24 week double-blind study of methotrexate in rheumatoid arthritis

    Clin Res

    (1985)
  • M.E. Weinblatt et al.

    Lowdose methotrexate compared with auranofin in adult rheumatoid arthritis. A thirty-six-week, double-blind trial

    Arthritis Rheum

    (1990)
  • H.J. Williams et al.

    Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • H Menninger et al.

    Randomised study of methotrexate vs. gold sodium thiomalate in patients with active rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • R.F. Willkens et al.

    Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • MEC Jeurissen et al.

    Methotrexate versus azathioprine in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1991)
  • M.H. Arnold et al.

    Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheumatoid arthritis: 3-year prospective study

    Br J Rheumatol

    (1990)
  • M Bell et al.

    A double-blind controlled trial of azathioprine and methotrexate in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1988)
  • H Hamdy et al.

    Low-dose methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A twenty-four-week controlled clinical trial

    Arthritis Rheum

    (1987)
  • D.T. Felson et al.

    The comparative efficacy and toxicity of second-line drugs for rheumatoid arthritis

    Arthritis Rheum

    (1990)
  • D.T. Felson et al.

    Use of shortterm efficacy/toxicity tradeoffs to second-line drugs in rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • A Schnabel et al.

    Side effects of 15 and 25 mg methotrexate/week for rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • H Mielants et al.

    The efficacy and toxicity of a constant low dose of methotrexate as a treatment for intractable rheumatoid arthritis: An open prospective study

    J Rheumatol

    (1991)
  • J.M. Kremer et al.

    The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis

    Arthritis Rheum

    (1986)
  • C.S. Fehlauer et al.

    Methotrexate therapy in rheumatoid arthritis: 2-year retrospective followup study

    J Rheumatol

    (1989)
  • RjR McKendry et al.

    Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis

    Arch Intern Med

    (1989)
  • F Wolfe et al.

    Termination of slow acting antirheumatic therapy in rheumatoid arthritis: A 14-year prospective evaluation of 1017 consecutive starts

    J Rheumatol

    (1990)
  • G.S. Alarcon et al.

    Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-term treatment

    Arthritis Rheum

    (1989)
  • G Singh et al.

    Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis

    J Rheumatol

    (1991)
  • M.E. Weinblatt et al.

    Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • J.M. Kremer et al.

    Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis

    Arthritis Rheum

    (1992)
  • N.O. Rothermich et al.

    Followup study of chrysotherapy

    Arthritis Rheum

    (1979)
  • R Rau et al.

    Retardation of radiologic progression in rheumatoid arthritis with methotrexate therapy

    Arthritis Rheum

    (1991)
  • J.M. Kremer et al.

    A long-term prospective study of the use of methotrexate in rheumatoid arthritis

    Arthritis Rheum

    (1988)
  • M Weinblatt et al.

    The effects of drug therapy on radiographic progression of rheumatoid arthritis. Results of a 36-week randomized trial comparing methotrexate to auranofin

    Arthritis Rheum

    (1993)
  • MEC Jeurissen et al.

    Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. A randomized, double-blind study

    Ann Intern Med

    (1991)
  • S Reykdal et al.

    Methotrexate treatment in rheumatoid arthritis: Effects on radiological progression

    Scand J Rheumatol

    (1989)
  • J Sany et al.

    Radiologic progression during intramuscular methotrexate treatment of rheumatoid arthritis

    J Rheumatol

    (1990)
  • P.S. Hanrahan et al.

    Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: Toxicity, efficacy and radiological progression

    Br J Rheumatol

    (1989)
  • GRV Hughes et al.

    Methotrexate treatment of Felty's syndrome

    Ann Rheum Dis

    (1990)
  • L.S. Allen et al.

    Treatment of Felty's syndrome with low-dose oral methotrexate

    Arthritis Rheum

    (1986)
  • C Isasi et al.

    Felty's syndrome: Response to low dose oral melhotrexate

    J Rheumatol

    (1989)
  • X Puechal et al.

    Treatment of Felty's syndrome with intravenous methotrexate

    J Rheumatol

    (1991)
  • J.J. Fiechtner et al.

    Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome

    Arthritis Rheum

    (1989)
  • S Wassenberg et al.

    Methotrexate treatment of Felty's syndrome

    Arthritis Rheum

    (1992)
  • F Guillemin et al.

    Worsening of Felty's syndrome with methotrexate

    Ann Rheum Dis

    (1991)
  • E.B. Larson

    Adult Still's disease. Evolution of a clinical syndrome and diagnosis, treatment, and follow-up of 17 patients

    Medicine

    (1984)
  • P Bourgeois et al.

    Low dose methotrexate for Still's disease in adults

    Clin Exp Rheumatol

    (1987)
  • Cited by (129)

    • Nanoparticle-mediated oxidative stress monitoring and role of nanoparticle for treatment of inflammatory diseases

      2019, Nanotechnology in Modern Animal Biotechnology: Concepts and Applications
    View all citing articles on Scopus
    1

    From the Department of Clinical Rheumatology, University of Lübeck, and Rheumatic Diseases Hospital, Bad Bramstedt, Germany.

    View full text