Renal Safety of NSAIDs Confirmed in Large Study of RA Patients

From Medscape Medical News
Alice Goodman

June 25, 2010 (Rome, Italy) — The use of nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors (coxibs), did not adversely affect renal function in patients with rheumatoid arthritis (RA), according to the results of one of the largest prospective studies to examine renal toxicity in RA patients, Swiss investigators reported here at the European League Against Rheumatism Congress 2010.

"In addition to the known gastrointestinal and cardiovascular risks, the renal safety of NSAIDs has long been questioned. When I started this study, I had a dark image of NSAIDs and renal function. This study shows that NSAIDs are safe in the large majority of RA patients, and these drugs should not be withheld for reasons of anticipated renal toxicity," stated lead author Burkhard Möller, MD, from Bern University Hospital in Switzerland.

The study population was a nested cohort of more than 4000 patients with at least 2 documented glomerular filtration rates (GFR) who were enrolled in the Swiss RA Registry. Patients were observed for a mean of 3.1 years. Mean drug exposure time was 2.5 years for conventional NSAIDs and 0.5 years for coxibs. The investigators looked at never or ever use of NSAIDs, coxib use, and cumulative dose effect.

At baseline, there were 1362 never users and 2745 ever users. About 75% were female, mean disease duration was 4 years, and more than 60% had been treated with methotrexate.

Never users had a slightly lower GFR rate at baseline, Dr. Möller said. However, over the course of 3 years, the slopes of the curves for never and ever users were similar. No effect on GFR was observed in the longitudinal analysis, with the exception of patients with stage 4 or 5 chronic kidney disease, who had a significantly greater mean loss of GFR (P = .045), which he called "a small marginal effect with use of NSAIDs."

The median annual change in GFR in ever users was 1.3 mL/min. Initiation or continuation of NSAID exposure, or exposure to the subgroup of coxibs, significantly modified the clearance rate. No single NSAID was associated with a decline in GFR in annual analyses.

"The annual change in GFR was no different with or without NSAID exposure. No obvious loss in GFR was seen with long-term use of NSAIDs, except in patients with a baseline GFR below 30 mL/min," he stated.

Dr. Möller said the strengths of this study include its size and the fact that it is based on real-life data.

He emphasized that "NSAIDs should be used responsibly. Control for GFR and repeat safety measures from time to time, but don't withhold these drugs for anticipated renal toxicity."

NSAIDs should not be used in stage 4 or 5 chronic kidney disease, and kidney function should be controlled in stage 3 patients started on NSAIDs, he added.

Viewpoint on Findings: Cautious Optimism

"This is an interesting study and basically corroborates previous work. Its size and general populations are very positive aspects of the study, and its conclusion — use NSAIDs responsibly — is appropriate, said Daniel Furst, MD, Carl M. Pierson Professor of Rheumatology at the University of California, Los Angeles in an interview with Medscape Rheumatology.

Dr. Furst added that it will be important to look at the frequency of follow-up, because changes in creatinine clearance tend to occur within the first 4 to 12 months.

"People remaining on the drugs will be those who had no early changes, so it is possible that we are looking mainly at those who tolerated the NSAID. Hence, it is not surprising that they appeared to have little deleterious effect," Dr. Furst noted.

"Seeing the full article and examining the details will be very important," he added.

Dr. Möller has disclosed no relevant financial relationships. Dr. Furst reports receiving grant/research support from Abbott, Actelion, Amgen, BMS, Genentech, Gilead, GSK, Nitec, Novartis, Roche, UCB, Wyeth, and XOMA; being a consultant for Abbott, Actelion, Amgen, BMS, Biogen Idec, Centocor, Genentech, Gilead, GSK, Merck, Nitec, Novartis, UCB, Wyeth, and XOMA; being an employee of: CORRONA; receiving honoraria from Abbott, Actelion, Amgen, BMS, Biogen Idec, Centocor, Genentech, Gilead, Merck, and Nitec; and being on the speakers bureau for Abbott, Actelion, and UCB.

European League Against Rheumatism (EULAR) Congress 2010: Abstract OP00007. Presented June 17, 2010.