News & Views Newletter
edited by Jack Nicholas, cornishpro@aol.co

PSORIATIC ARTHRITIS NEWS AND VIEWS
VOL. 3 ISSUE 4 March 15, 2003
PSORIATIC ARTHRITIS MEDICAL NEWS

U.S. DEBATES RISKS OF FOUR ARTHRITIS DRUGS
By LAURAN NEERGAARD .c The Associated Press

(This article refers to the FDA's Arthritis Drugs Advisory Committee scheduled March 5 review, of Arava , Remicade, Humira, and Enbrel side effects in patients with rheumatoid arthritis. More to come in the next issue on the results of this meeting.)

WASHINGTON (AP) - Increasing reports of major side effects - cancer and liver failure - are spurring the government to reassess the safety of rheumatoid arthritis drugs that gave patients unprecedented hope when they began hitting the market four years ago.

``These drugs have shown tremendous benefit, but they ... all have pros and cons,'' said Dr. Karen Weiss of the Food and Drug Administration.

Of the 2 million rheumatoid arthritis sufferers, thousands try one of the four drugs each year. Tuesday, the FDA's scientific advisers began two days of debate over how big a risk each medication poses and whether stronger warnings or restrictions are needed.

The consumer advocacy group Public Citizen is pushing for one of the medicines, Arava, to be banned. Reaction within FDA is mixed. An agency analysis posted on the FDA's Web site Tuesday recommends a ban - citing 54 U.S. cases of liver failure or damage and eight deaths linked to the drug.

``People should not use this,'' said Public Citizen's Dr. Sidney Wolfe, who contends Arava is far riskier than an equally effective, older alternative.

Higher-ranking FDA officials will tell agency advisers Wednesday that they disagree, citing additional analyses that argue there's no proof Arava is more dangerous than competing treatments.

``There are cases of liver injury that are possibly or probably related to use of Arava, but we also think it continues to have a place,'' said FDA drug chief Dr. John Jenkins. He said the FDA might find, however, that more safety restrictions were needed.

The FDA also is struggling to determine if three other medicines - Enbrel, Remicade and Humira - are linked to 170 cases of lymphoma, a hard-to-treat immune system cancer, reported since 1998.

Manufacturers argue patients already are adequately warned about possible side effects, and there's no proof the drugs are to blame.

``Causality is not easy to determine,'' said Dr. Francois Nader of Aventis Pharmaceuticals, Arava's maker. Meanwhile, ``the physicians need choices, and the patients need choices.''

Rheumatoid arthritis, which affects mostly women, is not the wear-and-tear joint damage that plagues the elderly. Instead, the immune system goes awry and attacks patients' own cartilage, causing pain and swelling and eventually destroying the joint. It typically strikes between ages 25 and 50, and within 10 years, about half of patients are too disabled to work.

Standard treatment is a cancer drug called methotrexate. For years, few options existed for patients who failed methotrexate or couldn't tolerate its side effects, including liver damage.

In 1998, new-generation treatments started selling. First came Arava, a chemical that blocks the overproduction of immune cells that inflame joints, similar to how methotrexate works.

Then came Enbrel and Remicade, biologically engineered drugs that sop up a different inflammation-causing protein, tumor necrosis factor or TNF. A third TNF inhibitor, Humira, won FDA approval last December.

From the start, FDA warned of serious risks. It urged doctors to check Arava patients regularly for liver damage, and stressed use of birth control because Arava could cause birth defects. All three TNF inhibitors carry warnings that they suppress the immune system enough to cause severe, even deadly, infections and theoretically could increase the risk of cancer.

Now, after four years of sales, the FDA has reports of 170 cases of lymphoma among users of the three TNF inhibitors.

It's hard to prove if the drugs play any role, Weiss cautioned. Rheumatoid arthritis itself increases lymphoma risk - RA patients get that cancer at two- to threefold higher rates than the general population. Plus, only 29 of the cases occurred during formal studies that allow full investigation.

``You can make a case that the incidence of lymphomas is in the range you would expect to see in rheumatoid arthritis,'' said Tom Schaible of Centocor Inc., Remicade's maker.

Dr. John Klippel of the Arthritis Foundation hopes the FDA meeting will help doctors and patients better compare each drug's different risks before choosing one. ``These remain very important drugs,'' he said.

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HOW MANY DRUGS ARE YOU TAKING?
By Gina Shaw WedMD Feature Reviewed By Brunilda Nazario, MD

If you're over 65, odds are you're taking at least five or six medications every day. Do you know what they're doing to your body? You probably don't, and your doctor might not either.

"The average person over 65 now uses seven different medications per day, four prescribed and three over-the-counter," says Andrew Duxbury, MD, associate professor of geriatrics at the University of Alabama at Birmingham and director of the senior care clinic at UAB's Kirklin Clinic. "There's never been a controlled study on a human being involving more than three drugs circulating in the body at the same time. So no one knows, scientifically, exactly what's going on in your body when you take seven, 10, or a dozen at a time."

Medication errors in seniors are among the most common preventable errors in the healthcare system today. About one in every three people over 65 will have some sort of adverse medication event that requires a hospital visit, according to Duxbury, and some 10% to 15% of all emergency room visits are related to medication reactions or drug interaction problems in seniors.

One Patient, Many Doctors - Part of the problem is that many people over 65 see multiple physicians. A typical 70-year-old man might see a family doctor for regular checkups, a kidney specialist to control his diabetes, and a cardiologist for his irregular heartbeat. "In some cases, one doctor will be treating a condition and add a medication, but fail to tell a patient that they should discontinue a different medication prescribed by another doctor, so they end up taking both," says Wayne K. Anderson, PhD, dean of the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, which has a specialized program in geriatric pharmacotherapy. "One doctor may not be aware of what other doctors are prescribing."

Good medications in bad combinations can be dangerous and even deadly. Statistically, a person taking eight medications can expect at least one drug interaction problem that will negatively affect his or her health, Anderson says. For example, if you're taking a medication that has blood-thinning properties and then begin to take aspirin on a regular basis, and your doctor doesn't know about both, it can put you in danger of uncontrolled bleeding. Some herbal medications -- which many doctors don't know their patients are taking -- can also influence the blood's ability to clot, causing further problems. That's just one possible set of interactions.

The wrong medications, or the right medications in the wrong combinations, can lead to a "cascade effect." Anderson recalls the story of a man whose doctor prescribed pain medication for his osteoarthritis. The medication caused nausea, for which he was prescribed anti-nausea medication. That drug caused tremors that looked like Parkinson's disease -- and things spun out of control. "The man was being treated by two or three different physicians. One of them prescribed medication for Parkinson's, which caused more nausea and more tremors, and an inability to sleep. So he was prescribed sedatives, which led to absent-mindedness, more shakiness, and dementia-like behavior," Anderson says. "He went from a gentleman who enjoyed his walks and getting the Sunday paper at the corner store to a man who was bedridden with a diagnosis of end-stage parkinsonism and senile dementia." Ultimately, a pharmacist discovered the out-of-control drug combination and notified the man's doctors. Fortunately, he regained normal function and was released from the hospital taking nothing more than Tylenol.

Get Your Drugs in Order - The message is clear: It's time to get your medication in order. Here are a few key principles of medication management for seniors and their families. (If a family member shows any evidence of memory problems, someone else should be in charge of their medications.)

First, make sure all your healthcare providers know all of the medications you're taking. "Every person, of any age, should carry a complete list of all the medications they take, by name and dose and dose schedule," says Anderson. Your list should include not only prescription medications, but also over-the-counter drugs and herbal remedies. Many herbal preparations can have significant interactions with prescription medications.

When a new medication is prescribed, ask what it's supposed to do and you're your dosage is. "The general rule is that you should start with the lowest possible dose and work up," Duxbury explains. "Ask your physician if he's starting with the smallest dose."

Be honest with your doctor about what you're taking. "You might get a prescription for blood pressure medication and find that you can't afford it, so you stop taking it -- but you don't tell your doctor," Duxbury says. "So you go back for a checkup and your blood pressure is still high, so you're prescribed a second medication. Eventually you'll end up in the hospital and the doctor has you listed as taking three or four different medications when you're really not taking anything. So the nurse administers all four at once, and you have a catastrophe." Get to know your pharmacist. "It's a good idea to fill all your prescriptions at a single pharmacy, and elders may be better off at a 'mom and pop' drugstore than a chain," says Duxbury. "If it's the same pharmacist behind the counter every time, who knows who their customers are and something about them, that person is much more likely to catch a problem." Purge your medicine cabinet on a regular basis. "Every six months to a year, take all your medications -- prescription, over-the-counter, herbal, everything -- out of your medicine cabinet, throw them into a brown paper bag, and take them to your doctor," Duxbury advises. "What he thinks you're taking, what's in your chart, and what's going down your throat are often three different things."

Published March 3, 2003. Wayne K. Anderson, PhD, dean, University at Buffalo School of Pharmacy and Pharmaceutical Sciences. Andrew Duxbury, MD, associate professor of geriatrics, University of Alabama, Birmingham. © 2003 WebMD Inc.

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TREATING PAIN WITH MEDICATIONS

In the past 20 years, a host of new pain medications has become available. These new formulations give people with chronic pain more options than ever. But all drugs can have side effects that limit how they're used.

Two strategies can guide your use of pain medications:

First, if you're taking pain medications, you'll want to find the lowest dose that controls your pain. The lower the dose, the fewer and less severe the side effects.

And second, it's often better to "stay ahead" of chronic pain by taking your medication at regular intervals, rather than waiting until the pain becomes intolerable. If the pain is predictable, as migraine pain can be, taking your medication before the pain begins may be the best approach.

The following are among the most common drugs used for chronic pain: Acetaminophen, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Capsaicin, Corticosteroids, Muscle Relaxants, Antidepressants, Anticonvulsants, Narcotics (Opioids), Tramadol, Anesthetic Nerve Blocks, Acetaminophen.

Example: Tylenol - Description: Acetaminophen is a safe and mild pain reliever when used in moderation. Side effects: If you drink alcohol regularly, high doses of acetaminophen can cause liver damage, so be sure to tell your physician if you drink.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) - Examples: Aspirin, ibuprofen and naproxen. Description: NSAIDs reduce inflammation. They also relieve pain, even if there's no inflammation. Side effects: Minor side effects associated with NSAIDs are common and include rash, nausea and heartburn; however, ulcer disease is the most common of the serious side effects. The risk of ulcers appears to be lower with newer NSAIDs, including celecoxib and rofecoxib.

Capsaicin - Trade name: Zostrix. Description: Capsaicin is a cream that is applied to the skin. Usually applied sparingly three or four times each day, capsaicin is used to reduce pain in the treated area. It is mostly used for nerve pain (neuropathy) or arthritis (in the fingers). Side effects: Capsaicin can cause burning sensation on the skin. Contact with the eyes should be avoided, as it is quite irritating.

Corticosteroids - Examples: Prednisone, methylprednisolone and dexamethasone. Description: Corticosteroids are anti-inflammatory drugs. They may be taken orally or injected directly into the site of nerve irritation or inflammation. In some cases of chronic back or leg pain caused by spinal stenosis, degenerative joint disease or disk disease, injecting corticosteroids into the spine (often along with an anesthetic) can reduce or eliminate the pain for weeks or months. Usually, no more than three injections per year are recommended because of the risk of side effects. Side effects: Regardless of how you take corticosteroids, the higher the dose and the longer the therapy, the greater your risk of side effects, including weight gain, diabetes, hypertension, facial puffiness, osteoporosis and infection. If corticosteroids are injected, side effects include discomfort, infection and thinning or discoloration of the skin at the injection site, but these problems are quite rare when injections are not frequent.

Muscle Relaxants - Examples: Cyclobenzaprine, methocarbamol and carisoprodol. Description: Muscle relaxants are particularly good for treating muscle spasm, which contributes to many cases of back pain. These drugs may reduce pain by acting directly on certain chemical messengers in the brain rather than by directly relaxing muscles. Side effects: Because muscle relaxants may act on chemical messengers in the brain, this may explain why they also cause drowsiness.

Antidepressants - Examples: Amitriptyline, nortriptyline, desipramine and doxepin (tricyclic antidepressants); fluoxetine (Prozac). Description: Antidepressants likely act on chemical messengers in the brain. By doing so, they can dull pain perception. In some cases, antidepressants work by treating accompanying depression that is making chronic pain more difficult to tolerate. These drugs sometimes work well even in doses too low to treat depression. Side effects: Side effects include dry mouth, sedation (drowsiness) and heart rhythm disturbances.

Anticonvulsants - Examples: Carbamazepine, phenytoin and gabapentin. Description: Anticonvulsants (antiseizure medications) may be particularly helpful for pain caused by neuropathy (nerve damage). Unlike antidepressant drugs, which affect certain chemical messengers in the brain, anticonvulsants also act directly on nerve tissue. Side effects: Sedation, liver damage and blood cell changes are the most common side effects that limit the use of anticonvulsants.

Narcotics (Opioids) - Examples: Codeine, hydrocodone, morphine and meperidine. Description: Narcotics are often used to treat severe, unrelenting pain, such as cancer pain. They are the most powerful pain relievers available and are generally used when other treatments have failed. Narcotics can be given by mouth, can be injected or can be administered by a patch, which delivers the drugs through the skin. In some cases, patients can wear a small device that feeds a trickle of narcotics into the spinal fluid through an implanted tube, or the painkiller can be delivered by a pump implanted directly into the abdomen. In general, narcotics are not used alone for chronic pain. They are often part of an approach that includes nondrug options (such as counseling and physical therapy), as well as other nonnarcotic drugs.

Research shows that many people who do not have adequate pain relief with narcotic analgesics are either receiving prescriptions that undertreat their pain or are not following the recommendations for those prescriptions because they fear side effects. For example, a recent study from the University of California at San Francisco interviewed cancer patients in their homes and found that fear of side effects was a major cause of inadequate drug use. In addition, fewer than a third of patients had been prescribed both as-needed and around-the-clock pain drugs as recommended by current guidelines.

Side effects: Unfortunately, narcotics can cause constipation, sedation and nausea. In susceptible persons (especially people with lung disease), these drugs may dangerously slow breathing. They can also be addictive and may require steadily increasing doses to remain effective; in the past, however, the risk of addiction for people with chronic pain may have been overestimated. Although side effects and the risk of addiction have caused some patients and their health-care providers to shy away from using narcotics, even when they may be the best way to treat severe pain, this anxiety about narcotics is gradually changing. More health-care providers are willing to prescribe these drugs when needed.

Tramadol - Trade name: Ultram. Description: Tramadol is a fairly new nonnarcotic pain reliever that acts in a similar way on the brain as narcotics do; it also affects levels of the chemical messenger serotonin in the brain. Side effects: Stomach upset, an increased risk of seizures (in susceptible persons) and harmful interactions with other drugs are the most common side effects.

Anesthetic Nerve Blocks - Examples: Lidocaine and bupivacaine. Description: Similar to novocaine, anesthetic nerve blocks may be injected into specific nerve bundles to interrupt pain signals before they are sent to the brain. The relief is usually temporary but may provide information that can lead to better treatment; if the nerve block works, for example, a second injection in the same area with a chemical that damages the involved nerve can block the signals and provide longer relief. Side effects: Side effects may include nerve damage and infection.

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MANAGING PAIN WITH NARCOTICS - OXYCONTIN AND ITS ALTERNATIVES
By Howard LeWine, M.D. Brigham and Women's Hospital

Narcotics are an essential part of pain management for many people. Doctors and their patients need to balance the improved quality of life pain relief brings against the potential for abuse and misuse. Narcotic abuse refers to a pattern of behavior where someone uses a drug to get "high," and as a result runs into problems at home, school or work. Someone abusing narcotics is prone to hazardous behavior, such as driving while intoxicated, getting into fights or running into trouble with the law. Narcotic misuse includes giving narcotics to others for whom they are not prescribed, selling prescription drugs, and stealing them.

Drug dependence is different. Dependence refers to the physical and psychological changes that occur when someone regularly takes a narcotic. A person may need larger amounts of a drug to achieve the same effect. The person could develop withdrawal symptoms if the drug is suddenly stopped.

There are situations in which the potential for drug dependence should be taken out of the equation. The most glaring example is end-of-life care. Increasing the dose of narcotics to relieve pain in a terminal patient might be limited by side effects and the risk of halting breathing, but worrying about the patient's becoming dependent on the drug should never be an issue.

Doctors sometimes will need to prescribe narcotics for a prolonged painful illness, postoperative pain, or a chronic pain syndrome. The patient may become dependent on the drug, but dependence is not always a bad thing as long as the gains are worth it. Doctors do pay attention to the possibility that healthy dependence could become unhealthy abuse.

Of the many narcotic pain relievers, OxyContin has been getting the most publicity. OxyContin, when prescribed and used appropriately, can be an important part of a successful pain-management program. When the pill is swallowed whole as designed, the active ingredient oxycodone is slowly released to relieve pain without creating a "high." This allows people to function in daily life.

But OxyContin can easily be misused. It has more abuse potential than many other narcotics because it is pure oxycodone, the tablets can contain very high doses of narcotic, and the tablets can be crushed to release the ingredients in a powder form that provides a much more immediately potent dose. So if you are taking this medication, never chew the tablets, and store them in a special, safe place.

OxyContin should usually be limited to the treatment of pain that is expected to last more than a few weeks. For most people with new severe pain, shorter-acting narcotics can be used. There are many choices, most of which contain a combination of two ingredients. Acetaminophen, aspirin, or ibuprofen is often combined with a narcotic such as codeine, hydrocodone, or small doses of oxycodone. Examples are acetaminophen with codeine, Vicodin, Vicoprofen, Percocet, and Percodan. People with gastritis and peptic-ulcer disease should note that Vicoprofen contains ibuprofen and Percodan contains aspirin. These medications also are used in people with chronic pain to help manage what is called breakthrough pain.

In people with cancer or chronic pain syndromes, using a long acting, slow-release narcotic preparation can prevent, or at least significantly decrease, the frequency and severity of breakthrough pain. The long-acting alternatives to OxyContin are oral sustained-release morphine sulfate (MS Contin, Avinza), methadone, and the fentanyl (Duragesic) skin patch. The morphine-sulfate preparations share similar problems with OxyContin in that they can be opened or chewed, but the incidence of abuse with MS Contin and Avinza has been much lower. Methadone works well for many people to provide steady pain relief with less of the "high." The fentanyl skin patch is expensive, but provides a steady amount of drug delivered to the bloodstream and, presumably, a steady amount of pain relief.

Because all of the narcotics work in essentially the same way, they all share the same side effects and potential for dependence. When used under careful medical supervision, these drugs can provide great relief and improve the quality of life in people with cancer or chronic pain conditions.

The company that makes OxyContin is working on a new tablet design. The goal is to create an easy-to-take oral medicine that continues to slowly release oxycodone over eight to 12 hours, but one that cannot be altered by chewing or crushing to release pure, short-acting oxycodone.

Howard LeWine, M.D., is chief editor of Internet publishing, Harvard Health Publications. He is a clinical instructor of medicine at Harvard Medical School and Brigham and Women's Hospital. Dr. LeWine has been a primary care internist and teacher of internal medicine since 1978.

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BEING A DOCTOR MEANS HAVING TO SAY YOU'RE SORRY
Laurie Barclay, MD Medscape Medical News

Neither doctors nor patients get the proper emotional support after being involved in a medical error, according to the results of a focus group analysis reported in the Feb. 26 issue of The Journal of the American Medical Association. The investigators suggest that doctors should make more of an effort to apologize to their patients, in addition to providing them with appropriate information regarding the nature and cause of the error.

"Health care institutions nationwide are developing ambitious programs to prevent medical errors," write Thomas G. Gallagher, MD, from the University of Washington School of Medicine in Seattle, and colleagues. "Yet, despite our best efforts, medical errors will inevitably occur."

Factors preventing full disclosure of medical errors to patients by physicians may include fear of a malpractice suit, concern about professional reputation, and feeling awkward or uncomfortable.

Of 13 focus groups held between April and June 2002, six involved only patients, four groups involved only physicians, and three groups included both patients and physicians. Of the 52 patients, 71% were female and 88% were white; average age was 60 years. Of the 46 academic and community physicians, 83% were male and 78% were white, and they had been in practice for an average of 16 years.

After reviewing transcripts of focus group discussions concerning a hypothetical medical error, the authors discovered that both patients and physicians had unmet needs regarding communication about errors. Patients wanted information about all harmful errors, including what happened, why it happened, how to improve the outcome, and how to prevent recurrences. Physicians agreed that harmful errors should be disclosed but were guarded in what they told patients about errors.

Although patients wanted an apology and other emotional support from physicians following errors, physicians were concerned that an apology might create legal liability. Physicians were also distraught over errors but did not know where to seek emotional support.

"The current response to medical errors may meet neither patients' desire for information about errors nor the needs of patients and physicians for emotional support following an error," the authors write. "Physicians should strive to meet patients' desire for an apology and for information on the nature, cause, and prevention of errors. Institutions should also address the emotional needs of practitioners who are involved in medical errors."

JAMA. 2003;289:1001-1007 Reviewed by Gary D. Vogin, MD

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IBUPROFEN BOOSTS BLOOD PRESSURE IN PATIENTS ON ACE INHIBITORS NEW YORK
(Reuters Health)

Ibuprofen can cause a significant elevation of systolic blood pressure in certain hypertensive patients taking angiotensin converting enzyme (ACE) inhibitors, researchers report in the February issue of the American Journal of Hypertension.

Ms. Ann Haig of GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania, and colleagues note that nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to attenuate the blood-pressure lowering effects of drugs including ACE inhibitors.

To investigate, the researchers conducted a double-blind study of 385 hypertensive patients stabilized on an ACE inhibitor. They were randomized to also receive daily, nabumetone 2000 mg, ibuprofen 2400 mg, celecoxib 400 mg or placebo. The doses, say the investigators, were "all maximal for the treatment of rheumatoid arthritis or other inflammatory conditions."

At the end of the 4-week treatment period, it was found that compared with placebo, ibuprofen caused significant increases in mean systolic (+6.5 mm Hg) and diastolic blood pressure (+3.5 mm Hg). The increases with nabumetone (+3.8/1.3 mm Hg) and celecoxib (+3.0/1.4 mm Hg) were not significant.

Furthermore, the proportion of patients with "systolic BP increases of clinical concern" was significantly greater in the ibuprofen group (16.7%) than in the nabumetone group (5.5%), the celecoxib group (4.6%) or the placebo group (1.1%).

The researchers point out that "the magnitude of the increase in BP" may depend on individual sensitivity, but conclude that in patients who need an ACE inhibitor and a NSAID, a choice "such as nabumetone or celecoxib, could minimize BP elevations."

Am J Hypertens 2003;16:135-139.

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IBUPROFEN REDUCES ASPIRIN'S HEART BENEFIT
By Jeanie Lerche Davis WebMD Medical News Reviewed By Brunilda Nazario, MD

If you're taking aspirin to prevent heart attack or stroke, listen up. A dose of ibuprofen could be reducing the aspirin's benefit -- possibly increasing your risk of dying. Best to take another type of painkiller, researchers say.

Aspirin is known to make blood-clotting platelets less "sticky" -- reducing risk of heart attack and stroke. A previous laboratory study has suggested that when ibuprofen (such as Advil) interacts with aspirin, this benefit of aspirin diminishes, writes Tom MacDonald, PhD, a researcher with the Ninewells Hospital and Medical School in Dundee, Scotland.

In his paper in this week's Lancet, Macdonald and colleagues report on over 7,000 patients with heart disease who were advised to take low- dose aspirin to protect against cardiovascular disease. Researchers looked at the death rates in this group, from heart disease and other causes. They also looked at death rates among those taking both aspirin and ibuprofen.

Those patients taking both aspirin and ibuprofen had nearly twice the risk of death from any cause -- and a 73% increased risk of death from heart disease, MacDonald reports. There was no increased numbers of deaths among those taking aspirin with other painkillers similar to ibuprofen.

While the findings are not conclusive, MacDonald suggests that patients take an alternative painkiller until more is known. "Furthermore, we also know that aspirin and ibuprofen taken together increases the risk of bleeding from stomach ulcers. So this combination may not only reduce the benefits of aspirin, but may also increase the risk of side effects."

SOURCE: Lancet, 2003

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Laughing is good exercise. It's like jogging on the inside.

Good Health to All,

Jack Nicholas
Newsletter Editor
Cornishpro@aol.com
Issue 2003 3/15/03 -4