Safety and efficacy of oral nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis : a six-month randomised study.

OBJECTIVE

To monitor the safety and efficacy profile of long-term treatment with diclofenac, nabumetone, meloxicam and celecoxib in patients with rheumatoid arthritis.

DESIGN AND METHODS

This randomised, prospective clinical trial included a total of 461 subjects (313 females and 148 males) with clinically diagnosed rheumatoid arthritis. Their average age was 46.9 +/- 14.4 years (range 20-69 years), and the average disease duration was 1333.7 +/- 992.85 days. Subjects were randomly assigned daily administration of one of the following: diclofenac 75-100mg, meloxicam 15mg, nabumetone 1000mg or celecoxib 200mg. During the 6-month treatment period, a monthly patient interview was conducted to evaluate drug efficacy and safety.

RESULTS

407 subjects successfully completed the 6-month treatment. Sixteen patients (12.2%) withdrew from the diclofenac group, 16 (12.2%) from the nabumetone group, 17 (11.8%) from the meloxicam group and five (9.1%) from the celecoxib group. Most withdrawals occurred during the first 3 months of treatment. Reasons for withdrawals in the first three groups were lack of efficacy (44.9%) and adverse effects (38.8%). For the celecoxib group, high cost (80%) was the main reason for withdrawal. Adverse drug reactions to NSAIDs mostly occurred at an early stage of treatment, with an incidence rate of 31.9% for the diclofenac group, 19.9% for the nabumetone group, 25.2% for the meloxicam group, and 7.27% for the celecoxib group. Clinical efficacy rates for the four NSAIDs were positively related to the length of treatment. During the first 4 months, diclofenac, meloxicam and celecoxib showed better efficacy than nabumetone. There were no significant differences in efficacy during the fifth and sixth months. The overall 6-month effectiveness rates were 68.8% for diclofenac, 59.8% for nabumetone, 67.6% for meloxicam and 69.1% for celecoxib.

CONCLUSIONS

Adverse drug reactions and their related withdrawals occurred mostly at an early stage of NSAID treatment, so it is crucial to strengthen pharmacovigilance during this period. Among the investigated NSAIDs, celecoxib did not prove to be superior to diclofenac, nabumetone or meloxicam with respect to its efficacy in the treatment of rheumatoid arthritis; however, it did show good patient compliance and safety profiles.