Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: A meta-analysis of randomized controlled trials
Version of Record online: 27 OCT 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 11, pages 3511–3521, November 2012
How to Cite
Tarp, S., Bartels, E. M., Bliddal, H., Furst, D. E., Boers, M., Danneskiold-Samsøe, B., Rasmussen, M. and Christensen, R. (2012), Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: A meta-analysis of randomized controlled trials. Arthritis & Rheumatism, 64: 3511–3521. doi: 10.1002/art.34644
- Issue online: 27 OCT 2012
- Version of Record online: 27 OCT 2012
- Accepted manuscript online: 25 JUL 2012 09:54AM EST
- Manuscript Accepted: 17 JUL 2012
- Manuscript Received: 9 NOV 2011
- Oak Foundation
- Mundipharma International
- Faculty of Pharmaceutical Sciences at the University of Copenhagen, and Copenhagen University Hospital, Frederiksberg
To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.
We performed a systematic search in Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBase via OVID, the Institute for Scientific Information Web of Science, and other sources. Eligible trials were parallel-group, randomized, placebo-controlled trials of oral NSAID therapy in RA patients for which there were extractable CRP data. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated from the differences in means of CRP levels between groups (active treatment minus placebo) divided by the pooled SDs. For the meta-analysis, a random-effects model was used to estimate the overall change in CRP level, and stratified analysis was used to examine differences among NSAIDs.
We included 19 trials of 10 different NSAIDs. Overall, NSAIDs showed no effect on the CRP level (SMD 0.01 [95% CI −0.03, 0.06], P = 0.62). However, the prespecified stratified analysis indicated varying effects on the CRP level according to the different NSAIDs; lumiracoxib caused a statistically significant and consistent (I2 = 0%) increase in the CRP level (SMD 0.13 [95% CI 0.01, 0.25], P = 0.037), whereas naproxen caused a statistically significant and consistent (I2 = 0%) decrease in the CRP level (SMD −0.11 [95% CI −0.20, −0.02], P = 0.022).
Overall, NSAIDs have no effect on the CRP level. However, the nonselective NSAID naproxen was associated with a significant decrease in the CRP level, whereas the cyclooxygenase 2–selective NSAID lumiracoxib was associated with a significant increase in the CRP level. This finding is interesting considering the suspected influence of NSAIDs on cardiovascular complications.