URINARY GLUCARIC ACID EXCRETION IN RHEUMATOID-ARTHRITIS - INFLUENCE OF DISEASE-ACTIVITY AND DISEASE-MODIFYING DRUGS

Objective-To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arth ritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. Methods-Patients with RA were treat ed with sulphasalazine, sodium aurothiomalate, or D-penicillamine in s tandard dose regimens, for 24 weeks. Patients with ankylosing spondyli tis (AS) or noninflammatory arthritis (NIA) acted as controls. The uri nary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatm ent. Results-Patients with RA had a slightly greater urinary GA:creati nine ratio than patients with AS or NIA at baseline; this increased du ring treatment with disease modifying antirheumatic drugs (DMARDs). Su lphasalazine treatment had a greater effect on GA excretion than sodiu m aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspep tidase concentration showed a weak correlation with GA excretion betwe en weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, an d articular index) were found not to correlate with GA excretion betwe en weeks 0-12 or 0-24. Conclusion-The increased excretion of GA in pat ients with RA receiving DMARD treatment is probably the result of an i ndirect effect on hepatic metabolism bearing no relationship to diseas e activity.