Millions of people suffer from arthritis and a host of arthritic and rheumatic conditions, which cause a great a deal of pain apart from loss of mobility. While NSAIDs (non-steroid anti-inflammatory drugs) are usually the first line of treatment, COX-2 inhibitors found favor as they had fewer side effects. Conventional painkillers like ibuprofen, paracetamol, aspirin and diclofenac often cause stomach problems including increased acidity, stomach ulcers and even bleeding in the stomach.
How do these drugs work?
COX-2 inhibitors work in a very different way from traditional pain killers. Prostaglandins in the body are implicated in causing inflammation, pain and swelling that are symptoms of arthritis (apart from other medical conditions). These are made by two different enzymes, COX-1 (cyclooxygenase-1) COX-2 (cyclooxygenase-2). Each has a different effect on the body: COX-1 has a protective effect on the stomach lining, while COX-2 is responsible for the body’s inflammatory response.
Ordinary NSAIDs block both COX-1 and COX-2 enzymes so they can cause gastrointestinal problems apart from reducing inflammation. However COX-2 inhibitors block only COX-2, serving to reduce pain and swelling while at the same time not affecting the stomach lining. In theory COX-2 inhibitors are better. That’s why when COX-2 inhibitors came into the market, many doctors and patients embraced this form of treatment as these drugs were gentler on the stomach while still being effective in affording pain relief.
Why are most COX-2 inhibitors now off the market?
Though a drug’s safety and efficacy is supposed to be seen to by the FDA, the fact of the matter is that it is the drug companies that have to conduct trials and present evidence. And the human tragedy is compounded by the fact that new medicines are big business for companies. Patients of arthritis have very limited alternatives as painkillers, particularly since, in the U.K., the use of diclofenac has also become restricted. Most pain killers and other medicines that are given for arthritis have many side effects or cannot be taken by patients who may be suffering from other ailments as well.
However, as reports filtered in that things were not as rosy as they seemed and studies came up linking cardiovascular death to these drugs, the pharmaceutical companies and FDA, which approved these drugs, went on the defensive. Two studies, APPROVe and VIGOR showed that COX-2 inhibitors were linked to increased risk of cardiovascular ailments, but the pharmaceutical companies just ignored these studies, as did the FDA. As a result the companies reaped a huge profit from the sale of these drugs. Then they got a wake-up call.
Deaths, recalls and lawsuits
An estimated 27,785 heart attacks and sudden cardiac deaths took place between 1999 and 2003 thanks to widespread of use of Vioxx. In august 2004, Dr. David Graham presented a study on 1.4 million Kaiser Permanente (a health maintenance organization) members that found patients who took the drug were more likely to suffer from heart problems. Merck had to pay the government $950 million to settle health care fraud allegations and $8.5 billion to settle various product liability lawsuits and another $6 billion in settlements.
Vioxx (rofecoxib), a popular COX-2 inhibitor was approved in 1999, but then voluntarily withdrawn in 2004 because research studies showed that patients who took the drug were more likely to die of cardiovascular problems or even sudden cardiac death than those who took other COX-2 inhibitors like Celebrex.
In 2005, FDA asked Pfizer to remove Bextra (valdecocib) from the market as well. The company had to keep $894 million to settle lawsuits. It also paid $2.3 billion to settle a U.S. Department of Justice probe. The lawsuit on Celebrex (celecoxib) is still ongoing and it is now sold with strict warning on its labels. All these drugs have been implicated in cardiovascular ailments, including heart attacks and strokes. Apart from Celebrex other COX-2 inhibitors available are Arcoxia (etoricoxib) and Dynastat (parecoxib).
What is worse is that Dr. Scott S. Reuben of Bay State Medical Center confessed that he had faked data in as many as 21 published research studies that showed favorable findings for both Vioxx and Bextra.
Are COX-2 inhibitors, by and large, a lost cause?
Researchers are now working on how to make this class of medicines better so that side effects are nullified. Professor Jane Mitchell of Imperial College London’s Faculty of Medicine has recently published research findings that show how these drugs actually work. The research findings point to the fact that COX-2 inhibitors are not found in the blood vessels, but instead in the brain, gut, kidney and thymus gland. Had these been found in the blood vessels it would have confirmed that the cardiovascular risks occurred because of the drug in the blood vessels. Earlier it was thought that the drugs were found in the blood vessels.
This research published in July 2013, in PLOS ONE, points to a better class of COX-2 drugs in the future, which will offer more targeted pain relief and also fewer side effects. Professor Jane Mitchell said: ‘Now we know the true sites of COX-2, we can begin to develop new ideas that will lead to better drugs for arthritis and cancer with fewer side-effects.
‘This study does not provide all the answers, but once we understand exactly how COX-2 affects the cardiovascular system we will be in a position to design new therapies. This will not be easy but all the tools are available and we could be looking at new leads within five to ten years.’
Meanwhile, if you have been prescribed any of the available COX-2 inhibitors you should discuss your treatment options and side effects with your doctor.