ab17_3

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

P. Angelis-Stoforidis¹, F.J.E Vajda², N. Christophidis¹

¹Department of Clinical Pharmacology, St. Vincent’s Hospital, Victoria; ²Australian Centre for Clinical Neuropharmacology, St. Vincent’s Hospital, Melbourne, Australia.

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.

Key words
Methotrexate polyglutamates, erythrocytes, polymorphs, rheumatoid arthritis, clincal efficacy.

Please address reprint requests and correspondence to: Pela Angelis-Stoforidis, Department of Clinical Pharmacology, St Vincent’s Hospital, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.