Etodolac: Return of an Arthritis Veteran

When covering doctors' struggles to prescribe in the wake of the Vioxx scandal--though it is fast becoming more accurate to say 'the COX-2 inhibitor scandal--a New York Times article discusses how the Veterans Affairs department has increasingly chosen to prescribe etodolac over Vioxx, Celebrex and Bexra. Stemming from a 2001 drug review, the department now prescribes etodolac at approximately triple the rate it prescribes COX-2 inhibitors and even recommends veterans switch to etodolac. The VA based its switch on clinical findings, suggesting a primary concern for veterans' safety (but it certainly helps that the drug is cheaper than the COX-2 inhibitors). The article raises the questions of who knew what when and the efficacy of so called "evidence-based drug reviews" but most importantly, the article examines where to go from here. Well, there are probably many ways to go and etodolac might be one of them.

First sold in 1991 as Lodine, etodolac is a lesser-known painkiller--possibly muscled off the medical radar by the financial clout of the COX-2 inhibitors. (Because it is now a generic drug, the VA department estimates they will save $40 million annually by turning to etodolac.) The drug itself is a nonsteriodal anti-inflammatory drug (NSAID). etodolac, like all other NSAIDs (including Celebrex, aspirin and ibuprofen) suppresses the prostaglandins, some of the chemicals causing inflammation; these same chemicals also involve the digestion process and explain why NSAIDs run the risk of indigestion, bleeding and ulcers. In contrast, the COX-2 inhibitor suppresses the cyclooxygenase enzyme, an enzyme emitted by inflamed cells.

Therefore, when the COX-2 inhibitors first came out, a major selling point was their ability to relieve joint pain and inflammation with a lower risk of stomach bleeding--as compared to NSAIDs like aspirin or ibuprofen. But after the recall, there was more and more talk about how the COX-2 inhibitor--heart risk notwithstanding--performed only equal to or just marginally better than older (and less expensive) drugs. This seems to apply to etodolac: a study recently published in the November issue of Gastroenterology used VA patients' records to find that when compared to Aleve, etodolac and Vioxx reduced the risk of stomach bleeding and ulcer by 60 percent. Similarly, a 1997 study compared etodolac to ibuprofen to find that etodolac produced greater pain relief at a lesser risk of ulcer and bleeding.

All these findings--for etodolac, for Vioxx, for ibuprofen--come from evidence-based drug reviews, a sort of study coming to the fore as a number of drugs for a number of afflictions multiplies. Right now, evidence-based drug reviews have no professional standards or expectations but they do strive to do two things: (1) directly compare how different drugs treat the same problem, i.e. how NSAIDs and COX-2 treat the inflammation of Rheumatoid Arthritis and (2) the individual side effects of these drugs.

By this measure, etodolac has done well so far; as Dr. Byron Cryer, the senior author of the Gastroenterology study reports, "in the 13 years of etodolac's use in the United Sates, there have been no reports of increases in cardiovascular events associated with this drug." But even still, because the drug was available before the explosion of new drugs and before such evidence based reviews became necessary, the drug will just now undergo the scrutiny of very cautious doctors. A study examining etodolac's heart risks is expected in about a month.

Article References
Meier, Barry, "Doctors, Too, Ask: Is This Drug Right?" New York Times. 12/30/2004, C1

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a692015.html, Site accessed 1/12/2005

Brune K, Hinz B. Selective cyclooxygenase-2 inhibitors: similarities and differences. Scand J Rheumatol. 2004;33(1):1-6.

Weideman R, Kelly K, Kazi S, Risks of clinically significant upper gastrointestinal events with etodolac and naproxen: A historical cohort analysis. Gastroenterology 2004 Nov; 127: 1322-1328.

DH Neustadt, "Double Blind Evaluation of the Long Term Effects of Etodolac Versus Ibuprofen in Patients with Rheumatoid Arthritis" J Rheumatol Suppl. 1997 Feb; 47:17-22.

http://www8.utsouthwestern.edu/utsw/cda/dept37389/files/195310.html, "Generic anti-imflammatory causes significantly fewer gastrointestinal complications than branded medications" Site accessed 1/17/2005.