Here come the ‘super aspirins’

Aside from Viagra (sildenafil) and Xenical (orlistat), no other drug in recent times has received as much media attention during its launching as the so-called "super-aspirins," Celebrex (celecoxib) and Vioxx (rofecoxib). The two drugs have gotten a lot of good press – and not just because they’ve been heavily advertised. They represent a big advance for people suffering from arthritis – a leading cause of disability all over the world. And that’s because, unlike so many arthritis drugs, they can ease pain without setting you up for a stomach ulcer. Their introduction has changed the arthritis treatment landscape so significantly, in fact, that the American College of Rheumatology (ACR) has revised its treatment guidelines early, giving the drugs a prominent place in the new protocol for minimizing osteoarthritic discomfort.

The two drugs are now among the best-selling medicines in the world. In the US, Celebrex is being manufactured by Pharmacia and Vioxx is a product of Merck & Co. Here in the Philippines, Celebrex is being jointly marketed by Pharmacia and Pfizer, Inc., and Vioxx, by Merck, Sharp & Dohme (MSD). According to IMS Health, Celebrex is Pharmacia’s biggest selling drug, generating sales of $2.3 billion in 12 months ending March 2001. Merck sold $1.7 billion of Vioxx in the same period, making it the company’s second-biggest drug behind its cholesterol-lowering medication, Zocor.

Anti-Arthritic Drugs

People who are experiencing mild to moderate arthritis pain are usually told by their doctors to try Tylenol and lifestyle therapies to see if they can get relief. If these approaches don’t work, the next move may be to take traditional non-steroidal anti-inflammatory drugs, or NSAIDs. These include Brufen (ibuprofen), Naprosyn (naproxen), Feldene (piroxicam), Voltaren (diclofenac) and others.

But the pain relief that NSAIDs provide brings with it a significant risk: gastrointestinal bleeding from ulcers that develop in the stomach lining. Consider that NSAIDs lessen pain by blocking production of prostaglandins, chemicals in the body that trigger inflammation. But prostaglandins don’t just cause inflammation. They also inhibit gastric acid secretion and produce thick mucous that lines the stomach wall. Decreasing prostaglandin production, therefore, diminishes the body’s defenses against ulcers. When these medications are used at high dosages for long-term treatments, the risk of side effects increases. Aside from gastrointestinal (GI) problems, NSAIDs can also sometimes disrupt kidney function.

That’s a special problem for older people, who are at greater risk for developing bleeding and also more likely to have osteoarthritis in the first place. In fact, the new guidelines note, no less than 20 to 30 percent of hospital stays and deaths related to ulcers among people over 65, can be attributed to NSAID treatment.

In other words, with NSAIDs, arthritis sufferers may have to make some difficult choices: either accept the bleeding risk, try to get by on a lower NSAID dose, or, while taking the medication, swallow an anti-ulcer drug – at an extra cost. Now, however, there are new alternatives – a new class of anti-inflammatory medicines called COX-2 inhibitors, or COXIBs, to which Celebrex and Vioxx belong. COXIBs are designed to have significantly less serious gastrointestinal side effects than traditional NSAIDs.

Indeed, in numerous studies done to evaluate the efficacy and safety profile of these drugs, they have proven to be as effective as the traditional NSAIDs, but have caused fewer complications. In fact, in patients over 65, COX-2 inhibitors are becoming the first-line treatment for osteoarthritis.

Side-Stepping Side Effects

Until the early 1990s, researchers believed that NSAIDs worked by blocking an enzyme called cyclo-oxygenase or COX. However, researchers now know that there are at least two versions of the enzyme, and these are COX-1, which is believed to be the enzyme that protects your stomach lining, and COX-2, which is the enzyme believed to be involved in pain and inflammation.

When researchers realized that NSAIDs likely blocked both versions of the COX enzyme, the quest was on to develop a more selective pain reliever – one that would block pain yet not harm the gastrointestinal lining. Celebrex was the first of this new class of drugs to go on the market. It was approved by the US Food andDrug Administration (FDA) in 1998 for osteoarthritis and rheumatoid arthritis. Vioxx, approved in 1999, is prescribed for acute pain and osteoarthritis, and more recently, for rheumatoid arthritis, as well. Short term studies do indicate that these drugs substantially lower the risk of ulcers compared to the risk among those taking other NSAIDs.

And so the World Health Organization (WHO) has decided to create a new class of drugs called COXIBs, made up of the COX-2 inhibitors. This is to differentiate these new drugs from conventional NSAIDs.

As helpful as the COX-2 inhibitors or COXIBs are for treating arthritis, they can still have adverse side effects. For example, a recent study published in the American Journal on Therapeutics reported that COXIBs, like NSAIDs, can also lead to destabilization of blood pressure control and other cardiorenal events in patients being treated with an anti-hypertensive medication. Those who were receiving Celebrex, however, experienced less edema (swelling) and less destabilization of blood pressure control compared with those receiving Vioxx. But if you have osteoarthritis or rheumatoid arthritis and are at high risk for GI complications (or can’t tolerate NSAIDs because of GI side effects), a COX-2 inhibitor may indeed be a good alternative.

But before making that decision, consider the following:

• COXIBs generally should not be taken if – as a result of taking aspirin, other NSAIDs or sulfa drugs – you’ve had hives, asthma, or an allergic reaction. If you have asthma, be cautious about taking these drugs.

• If you have known cardiovascular disease or are at risk for stroke or blood clotting, talk with your doctor about whether COXIBs are appropriate medications for you.

• These drugs do appear to have similar risks for kidneys as do comparable NSAIDs, so precautions should continue to be observed when considering these drugs in patients with kidney problems.

• COXIBs are drugs that are new. Sometimes, side effects not encountered in studies may become apparent when new drugs receive wider and longer consumer use.

Super-Aspirins?

Describing Celebrex and Vioxx as "super-aspirins" has raised a few eyebrows. First of all, they’re not aspirin. They do have pain-relieving and anti-inflammatory effects similar to those of aspirin, but, unlike aspirin, they don’t make your blood less likely to clot. Neither Vioxx nor Celebrex has shown aspirin’s heart-protecting benefit. Therefore, the COXIBs are not substitutes for aspirin in the prevention of heart attack or stroke.

In addition, they aren’t necessarily more powerful. For example, in clinical trials, Celebrex offered comparable arthritis pain relief to the prescription-strength NSAID, Naprosyn. Developers of these COX-2 inhibitor drugs or COXIBs say the term "super" applies more to what these drugs don’t do – they don’t appear to harm stomach and intestinal linings as much as the regular NSAIDs do.

But COXIBs may prove "super" for another reason: research has shown that COXIBs may also play an important role in the genesis and progression of Alzheimer’s disease and colon cancer. Indeed, there is some evidence to support the hypothesis that COXIBs may be a credible treatment option for Alzheimer’s disease and that they may prove to be a disease-modifying therapy. If so, this would be a major advance over current therapies, which provide only symptomatic relief. Results of a large-scale study to evaluate the impact of Vioxx in Alzheimer’s is expected to be announced next year.

COXIBs may also prove useful in certain types of colon cancer. Research done in animals has shown that COXIBs significantly reduced the number of adenomatous polyps – which are known to be pre-cancerous lesions. Because of these and similar studies, clinical trials of COXIBs in the prevention of colon polyps are now underway in humans. Results are expected in a few years.

Safe or Suspect?

For now, arthritis specialists say that COXIBs are viable options for people who have not responded well to older NSAIDs. But it should be borne in mind that these drugs are not for everyone, nor are they effective in all forms of arthritis. The ACR guidelines for the management of osteoarthritis identify COXIBs as especially advantageous to patients:

• whose osteoarthritis has an inflammatory component;

• those with moderate or more severe pain; and

• patients who may require combination therapy.

Those at greatest risk for complications include people over age 60, those with other chronic diseases, smokers, people with prior history of ulcers and those using other NSAIDs or cortisone-like drugs. Also people with allergies to sulfonamide drugs or aspirin should not take COXIBs. Furthermore, scientists stress that COX-2 inhibitors are no more effective at relieving pain or inflammation than other NSAIDs. And anyone taking these drugs should work closely with a physician to understand the risk factors and to watch for potentially dangerous side effects.

But, if you’re managing your osteoarthritis quite well with weight maintenance, low-impact exercises and adequate rest, and your current pain medicine is giving you relief without troublesome side effects, then stick with what you’re doing. However, if you’re one of the two percent to four percent of people who develop ulcers or other digestive tract problems from taking high doses of NSAIDs, then talk to your doctor about trying these new drugs. Because of their safety advantage, COXIBs are godsend for people with osteoarthritis who have developed stomach problems by taking traditional NSAIDs. Maybe, for that alone, they deserve to be called "super-aspirins"!