title: The effect of methotrexate on improving serological abnormalities of patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  MTX appears to be effective for improving serological abnormalities frequently observed before disease flares in SLE patients on a prednisolone taper.
authors.affiliation: Rheumatic Disease Center, Kurashiki Medical Center, 250 Bakuro-cho, Kurashiki, Okayama 710-8522, Japan. smutakata@mub.biglobe.ne.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Aita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yoshinaga
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000974:Antibodies, Antinuclear; D003176:Complement C3; D003181:Complement C4; D007166:Immunosuppressive Agents; D004247:DNA; D008727:Methotrexate