The effect of methotrexate on improving serological abnormalities of patients with systemic lupus erythematosus

This was an open-labeled, prospective, control study to determine the efficacy of methotrexate (MTX) for improving serological abnormalities in patients with systemic lupus erythematosus (SLE).

Thirty patients with a low serum complement and/or high anti-double-stranded DNA (dsDNA) antibody levels during a prednisolone taper received MTX orally at a dose of 7.5 mg/week over 12–18 months (MTX group). Eighteen SLE patients were selected as controls (control group). At the time of entrance into the study, all patients were receiving <15 mg/day of prednisolone. The C3, C4, and immunoglobulin (Ig)G, IgA, and IgM levels were measured using a turbidimetric immunoassay. The anti-dsDNA antibody level was measured using the Farr assay.

Significant increases in C3 and C4 levels and significant decreases in anti-dsDNA antibody, IgG, IgA, and IgM levels from baseline were observed for 3–18 months after the trial in the MTX group but not in the control group. At the end of the study, C3 and/or C4 levels in 96.7 % of the MTX patients and 33.3 % of the control patients were normalized or elevated (p = 0.0001), and anti-dsDNA antibody levels were normalized or lowered in 24 of the 26 MTX patients (92.3 %) and in 50.0 % of the control patients (p = 0.0022). In addition, a significant reduction in SLE Disease Activity Index (SLEDAI) score and a prednisolone-sparing effect were observed for the MTX group but not the control group. A significant increase in mean corpuscular volume of red blood cells, which is indicative of an anti-folic-acid metabolic disorder induced by MTX, was observed only for patients in the MTX group. Five patients (16.7 %) discontinued MTX treatment because of disease flare, and another three (10.0 %) discontinued due to treatment side effects.

MTX appears to be effective for improving serological abnormalities frequently observed before disease flares in SLE patients on a prednisolone taper.