Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis

Clin Exp Rheumatol. May-Jun 1999;17(3):313-20.

Abstract

Objectives: To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects.

Methods: Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay.

Results: E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15).

Conclusion: The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Blood Cells / chemistry*
  • Cell Separation
  • Drug Therapy, Combination
  • Erythrocytes / chemistry
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / therapeutic use*
  • Leukocytes, Mononuclear / chemistry
  • Linear Models
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / analogs & derivatives*
  • Methotrexate / blood
  • Methotrexate / therapeutic use
  • Middle Aged
  • Polyglutamic Acid / adverse effects
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / blood
  • Polyglutamic Acid / therapeutic use

Substances

  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Polyglutamic Acid
  • methotrexate polyglutamate
  • Methotrexate