Methotrexate

Methotrexate (MTX) is a folate antagonist that has profound anti-inflammatory activities. Accordingly, MTX inhibits the activity of the proinflammatory cytokine interleukin (IL)-1p by blocking its binding to the IL-1 receptor (Sauder et al. 1993). On the other hand, the synthesis and release of IL-ip is not affected by MTX (Boehm et al. 1998). Moreover, there is evidence that patients with LE have a defective IL-1 receptor antagonist synthesis, which results in impaired down-regulation of this proinflammatory mediator (Hsieh et al. 1995). In addition to IL-1, MTX also inhibits other proinflammatory cytokines, such as IL-6 and tumor necrosis factor (TNF)-a, which, via activating B cells, are involved in the regulation of immunoglobulin production in patients with SLE (Linker-Israeli et al. 1991).

Most studies using MTX for the treatment of LE have been performed in patients with SLE. Apparently, MTX is helpful in treating synovitis and mild forms of SLE but seems not to be very effective for organ-threatening disease (Carneiro and Sato 1999). However, promising studies on MTX for the treatment of refractory CLE have been published. Twelve patients with CLE refractory to antimalarials or low-dose oral glu-

Table 30.1. New therapeutic modalities for lupus erythematosus

Immunomodulating drugs

Biological agents

Methotrexate

INF-a

Calcineurin inhibitors

Anti-CD4

Mycophenolate Mofetil

Rituximab

Leflunomide

CTLA-4Ig

Anti-B7

Anti-IL-10

Anti-TNF-a

LJP-994

Anti-C5

Antibiotics

Tazarotene

Cefuroxime Axetil

Sulfasalazine

Phenytoin

Dehydroepiandrosterone

Intravenous Immunoglobulin

Plasmapheresis and immunoadsorption

Stem cell transplantation

Other experimental therapies

Anti-IL-10, anti-interleukin-10; INF-a, interferon-a; anti-TNF-a, anti-tumor necrosis factor-a.

cocorticosteroids were switched to MTX therapy (Boehm et al. 1998). On weekly administration of 10-25 mg MTX, marked improvement was observed in 10 of 12 patients. In 2 patients, the skin lesions cleared within 4 weeks, whereas most patients improved after an average of 6 weeks. Concomitant permanent or temporary treatment with systemic corticosteroids was necessary in six patients. Five patients showed long-term remissions of 5-24 months and a decrease in elevated circulating autoantibodies. All patients tolerated low-dose MTX treatment very well, and no withdrawal due to side effects was necessary. In two patients, MTX administration was discontinued because of lack of efficacy. Another recently published study showed complete clearing of skin lesions in one patient with severe SCLE refractory to therapy with antimalarials and corticosteroids (Kuhn et al. 2002).

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