Treatment of Juvenile Rheumatoid Arthritis with Diclofenac Sodium

Abstract

Diclofenac sodium was investigated in the treatment of juvenile rheumatoid arthritis (JRA). The pharmacokinetics of diclofenac in children aged 2-7 was assessed. Seven patients were included in a single-dose trial to determine plasma levels and renal elimination of diclofenac sodium. Venous blood samples were taken at 0, 0.5, 1, 2, 4 and 6 hours after administration of a 25 mg enteric-coated Voltaren® tablet. Urine was collected before and 0-6 and 6-12 hours after tablet ingestion. Maximum concentrations ranged from 0.79 to 4.25 μg/ml, and were found between 0.5 and 2 hours. Renal elimination of total diclofenac ranged from 5.4 to 10.2 % of the oral dose in 6 of the 7 patients. The youngest patient (2 years) had a lower elimination rate (2.25%) during the 12 hours observed. The values for children over 2 years corresponded to the range measured in adults.

The pharmacokinetic study was followed by a placebo-controlled study with diclofenac sodium and acetylsalicylic acid (ASA) for 2 weeks in 45 hospitalized patients aged 3-15 years. The patients were randomly assigned to either: DS 2-3 mg/kg/day, microcrystallized ASA 50-100 mg/kg/ day, or placebo matching diclofenac.

Global evaluation of therapeutic efficacy showed improvement in 73% of the patients in the diclofenac group, in 50 % of the ASA group and in 27 % of the placebo group. A statistically significant difference between these groups was found (p<0.05). The sum of grades of joint tenderness decreased during the 2 weeks in 67 % of patients in the diclofenac group, in 56% of the ASA group and in 36% of the placebo group. The average number of tender joints per patient decreased with diclofenac and with ASA, but increased with placebo.

The weekly laboratory tests (including complete blood count, kidney and liver tests) showed no pathological changes except in one patient treated with ASA, who had an increase in transaminase values. Four patients treated with ASA were excluded due to poor tolerance, while no adverse effects occurred in patients receiving diclofenac sodium. One patient in the ASA group and one in the placebo group were excluded due to worsening of the clinical status.