Methotrexate Treatment of Rheumatoid Arthritis Decreases Purine Enzyme...

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Methotrexate Treatment of Rheumatoid Arthritis Decreases Purine Enzyme

Activity

NEW YORK (Reuters Health) Dec 06 - Rheumatoid arthritis patients treated

with methotrexate experience significant decreases in the purine enzyme

activities of adenosine-deaminase (ADA), purine-nucleoside-phosphorylase

(PNP), and hypoxanthine-guanine-phosphoribosyltransferase (HGPRT), according

to a report in the December issue of the ls of the Rheumatic Diseases.

However, these effects do not seem to correlate with treatment efficacy.

Dr. R. F. J. M. Laan and colleagues from the University Medical Center St.

Radboud, Nijmegen, the Netherlands, examined purine metabolism during

treatment with methotrexate in 103 rheumatoid arthritis patients. In

addition, the relation of purine metabolism to the efficacy and toxicity of

methotrexate treatment was studied.

The patients were given an initial methotrexate dosage of 7.5 mg/week, and

this was increased to a maximum of 25 mg weekly as necessary. The team

measured the purine enzyme 5'-nucleotidase (5'NT), PNP, HGPRT, and ADA at

baseline, 6 weeks, and 48 weeks.

Values of 5'NT and PNP at the start of the study were 16.9 and 206.8

nmol/1,000,000 mononuclear cells per hour, respectively. The authors note

that HGPRT and ADA activities were low, at 8.7 and 80.3, respectively.]

There were no significant changes in purine enzyme activities at 6 weeks.

There was a decrease in the enzyme activities of ADA (-21.6), PNP (-78.9),

and HGPT (-2.0) after 48 weeks of treatment with methotrexate.

" Theoretically, decrease of ADA and PNP would lead to increment of adenosine

and subsequent anti-inflammatory effects. Unfortunately, we could not find

an association between the decrease of ADA and PNP and the efficacy of

methotrexate treatment in this study, " Dr. Laan and colleagues report.

" In contrast, enzyme activity of 5'-NT showed a decrease in the subgroup of

patients discontinuing methotrexate treatment because of hepatotoxicity. "

The researchers say more work is needed to determine the role of purine

metabolism in rheumatoid arthritis.

Ann Rheum Dis 2002;61:1060-1064.