Newer... Maybe Better: Biologics

February 6, 2006:- One of the biggest problems with many drugs is that they are nonspecific. While they are "fixing" what ails you, they also are affecting other parts of your body, often with unpleasant or dangerous side effects. Enter biological response modifiers (biologics for short), a potentially exciting new class of drugs derived from living organisms that are designed to target specific components of the immune system -- rather than the immune system as a whole -- with the goal of controlling serious disease while minimizing side effects. These drugs have been in use for some time in the treatment of rheumatoid arthritis (RA) -- infliximab (Remicade) is a name that should sound familiar -- and are starting to make their way into other areas.

The good news: Drug companies are opening their minds to the dangers of side effects. The bad news -- biologics are not quite there just yet, because they have been associated with adverse reactions including life-threatening infections and malignancies.

HOW THEY WORK

An exciting difference in biologic drugs versus most current medications is that they offer more than symptomatic relief -- they focus on underlying issues that cause symptoms. Noted Texas rheumatologist and author of Arthritis Without Pain (Sarah Allison), Scott J. Zashin, MD, has been using biologics for some time in the treatment of rheumatoid arthritis. He told me that three biologic agents -- etanercept (Enbrel), adalimumab (Humira) and infliximab (Remicade) are often effective in controlling RA in people who do not respond to conventional medications known as disease-modifying drugs (DMARDs).

Enbrel, Humira and Remicade work by blocking a substance manufactured by the immune system called tumor necrosis factor (TNF). People with RA and related inflammatory diseases -- including juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and psoriasis -- have too much TNF in their bodies. This overwhelms the immune system's ability to control inflammation, resulting in painful, swollen joints or, in the case of psoriasis, redness, itching and thick, silvery scales on the skin. Note: These medications are approved for RA and psoriatic arthritis... Humira and Remicade are also approved for ankylosing spondylitis... Remicade is approved for Crohn's disease and ulcerative colitis, etc. They are also used on an off-label basis for those inflammatory problems for which they are not approved.

TNF-blocking biologics are essentially man-made versions of proteins that the body produces naturally whose job it is to bind to and deactivate TNF molecules before they can do their damage. This interrupts the chain of events that leads to some forms of inflammation, and much of its resulting pain and damage.

PROS AND CONS OF BIOLOGICS FOR RA

According to Dr. Zashin, each of the three primary biologic drugs for RA (which are essentially blocking agents) have their pluses and minuses. A particular minus is that they can weaken the immune system...

1. Enbrel. Given by self-injection under the skin once or twice a week, Enbrel can provide rapid relief, often with the first shot. Dr. Zashin reports that relief tends to come faster with Enbrel than with Humira. With both Enbrel and Humira, injection site reactions that include pain, redness and infections are a concern, and, as mentioned above, all three biologics can weaken the immune system. Alert your physician at the first sign of any infection.
2. 
   Humira. This drug is also administered by injection, but a significant advantage is that shots are required on average only twice a month. In his practice, Dr. Zashin sees fewer upper respiratory infections caused primarily by the suppression of the immune system with Humira than with Enbrel. However, he adds that this is only his own experience, and research has yet to corroborate this effect.
3. 
   Remicade. Dr. Zashin recommends Remicade only when Enbrel and Humira prove ineffective. This drug must be given intravenously and administration takes about two hours. It is usually given three times during the first three weeks of treatment, and every eight weeks thereafter. Dr. Zashin cautions that with IV administration, there is a small but real risk of infusion reactions. Remicade is also considerably more expensive than the other biologics and brings with it similarly dangerous side effects. Remicade also has been approved for use in the treatment of Crohn's disease and ulcerative colitis.

A fourth biologic, anakinra (Kineret), is also available, but in Dr. Zashin's opinion, it is less effective than the others. Newly approved abatacept (Orencia) is a second-generation biologic that works differently from the TNF-blockers because it targets a different element of the immune system. Only time will tell whether this new medication is "safe and effective." Keep in mind that "safe and effective" is a category description that the FDA uses, not a guarantee that the drugs will be safe for all -- or safe in the long term.

A RISK FOR SERIOUS SIDE EFFECTS

As with any drugs that affect the immune system, Dr. Zashin warns that biologics have a serious downside. Risks that he mentions include...

Serious infections, including tuberculosis and sepsis
Nervous system diseases, such as multiple sclerosis
Blood problems
Heart problems (for example, congestive heart failure)
Allergic reactions
Malignancies, including lymphoma

Also, Dr. Zashin warns that the long-term effects of these drugs are simply not known. If you are taking a biologic, you must be very careful to meet regularly with your doctor to monitor your progress and any side effects.

TREATMENT MUST BE CAREFULLY INDIVIDUALIZED

RA can be a devastating, crippling disease, and some sufferers look on biologic medications as lifesavers. On the other hand, not everyone with RA needs to take biologics, warns Dr. Zashin. These are serious drugs that should be used only when they are absolutely necessary, and some people may be able to get by with nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, and more natural treatments. Given that NSAIDs are also associated with bleeding gastritis, liver and kidney complications, Daily Health News contributing editor Andrew L. Rubman, ND, encourages individuals to go natural first and save the drugs as a path of final resort.

The most important thing is to carefully individualize treatment, emphasizes Dr. Zashin. While one person with RA needs only NSAIDs, another might experience such rapidly developing damage that early and aggressive intervention with biologic medications is warranted.

Future Potential for Biologic Drugs

While biologic drugs are still used primarily for RA, they are also prescribed increasingly for other inflammatory diseases such as psoriasis, ulcerative colitis, Crohn's disease and psoriatic arthritis. As time goes on, he anticipates that more new biologic drugs will come on the market, and they may gradually become less expensive and able to be taken orally. Hopefully, they will be safer, as well.

Be well, Carole Jackson, Bottom Line's Daily Health News