Methotrexate use in systemic lupus erythematosus

Abstract

Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.

Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

“…This systematic literature review yielded 22 studies reporting discontinuation rates due to side effects in patients with SLE taking MMF, MTX, AZA, CYC, or CsA (Table 2) [17, 18, 22–27, 29, 32–36, 38, 39, 45, 46, 50, 51, 53, 54]. Overall, these rates were generally similar across treatments.…”

“…Eight studies analyzed AZA, reporting rates from 2.3% to 21.8% across study types [18, 23, 32–35, 39, 54]. Only three studies reported discontinuation rates due to AEs in patients taking MTX, with a range of 8.3% to 12.2% [29, 53, 54]. …”

Management of systemic lupus erythematosus (SLE)

“…Methotrexate is a cytotoxic drug of the folate antagonist group, which when used in the context of SLE has beneficial immunosuppressant effects, even when prescribed with folic acid. The effects of methotrexate on cytokine profiles in mouse models of SLE have been documented [18] but there have as yet been relatively few trials of methotrexate in humans [19–22]. It seems to be effective for treatment of skin, joint and muscle manifestations; however, its use in the presence of renal or CNS lupus has not been studied.…”

Uso de metotrexato en pacientes con lupus eritematoso sistémico

“…La explicación está en primer lugar, en la falta de respuesta satisfactoria al tratamiento previo, en lo que se refiere a manifestaciones articulares y cutáneas, y muy relacionado con esto, en la necesidad de usar dosis de corticoesteroides no deseables y desproporcionadas a las manifestaciones predominantes en esa etapa evolutiva como eran las señaladas; en segundo lugar, porque durante un largo tiempo el MTX no se consideró una alternativa válida para ser usada en pacientes lúpicos. Sin embargo, y como ya se señaló, la progresiva experiencia internacional ha permitido orientar su uso precisamente en estas manifestaciones y más aún si no ha habido una respuesta satisfactoria a los corticoides, antimaláricos o inmunosupresores [4][5][6][7][8][13][14][15][17][18][19][20][21] .…”