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Conquering inflammatory diseases

6/23/2003 5:10 PMBy Bruce Sylvester
UPI Science News
New York

New, nature-based medical treatments are on the verge of making breathtaking strides against a host of chronic diseases, such as psoriasis, arthritis and possibly even multiple sclerosis, experts have told United Press International.

A class of pharmaceuticals called "biologic" therapies -- drugs derived from living cells instead of synthesized chemicals -- promises to change radically the treatment of diseases caused by inflammation of the body's tissues. Four new drugs either on the market or in prospect are leading the way in the field.

This development has been made possible, experts said, by painstaking progress in the fields of genetics, microbiology and bioengineering, all of which have led to the development of medicines that can interfere with inflammation at the molecular level.

"Many inflammatory diseases seem to have a genetic component, and now we see that many are triggered by other processes, some in the workings of the immune system," said Dr. Anthony Gaspari, professor of dermatology at the University of Maryland in Baltimore.

One such process, Gaspari explained, involves the malfunction of cytokines -- proteins the body uses to trigger inflammation. Sometimes, the trigger can backfire and lead to the over-production of skin in psoriasis, the destruction of the myelin -- the cells surrounding nerve fibers -- in multiple sclerosis and the abnormal growth of connective tissue in the MS-like illness, scleroderma.

All of these chronic and progressive disorders seem to be rooted in an internal biochemical mechanism that can be addressed by an individually tailored biologic treatment, Gaspari told UPI at a recent American Medical Association briefing on the new therapies.

"So what is now proving so potent for rheumatoid arthritis, psoriatic arthritis and psoriasis might be leading us to new therapies for the other, apparently related disorders, like MS and scleroderma," he said.

Until recently, only toxic drugs such as methotrexate were available for patients with moderate-to-severe psoriasis. In less severe cases, skin creams and ultraviolet light therapy often could be used successfully.

"Biologic therapies now give us a powerful means to confront this often debilitating condition," Dr. Kenneth Gordon, associate professor of dermatology at Loyola University Medical Center in Maywood, Ill., told UPI. "So far, we haven't seen significant long-term side effects, and we will keep our eyes open for them. Biologics are our future in this field -- for the next decade and maybe beyond."

In the case of psoriasis, which afflicts about 5 million Americans, biologics block the inflammatory response that leads to overproduction of skin cells. The disease is characterized by various degrees of red, scaly patching of skin.

Patients receive the medications by injection -- either subcutaneous, or under the skin, or intramuscular -- once a week or every other week. This represents an improvement over the current, twice-daily applications of creams and ointments, which can be cosmetically unacceptable or otherwise unpleasant.

The four new biologic treatments for psoriasis are sold -- or will be sold -- under the brand names Amevive, Raptiva, Remicade and Enbrel.

Amevive, manufactured by Biogen Inc., of Cambridge, Mass., was approved by U.S. Food and Drug Administration last January. Clinical studies showed it reduced symptoms of psoriasis by at least 75 percent in 21 percent of patients after three months. Amevive inhibits the activity of the immune system's T-cells in what is called "remittance therapy." A patient receives treatment for 12 weeks and then is off for 12 weeks.

One possible problem is whether remittance therapy will cause long-term effects to the immune system, and the FDA has recommended further study to detect such adverse effects.

Raptiva, manufactured jointly by Genentech Inc., of San Francisco and Xoma of Berkeley, Calif., was submitted to the FDA for approval in December 2002. It is expected to be available later this year. Like Amevive, it inhibits T-cell activity. A trial involving 556 patients indicated weekly injections cut psoriasis symptoms by 75 percent or more in 27 percent of patients after three months of treatment and by 50 percent or more in 59 percent of patients.

Looking at both medications, Jason Kantor, a pharmaceuticals industry analyst at W.R. Hambrecht and Co. in San Francisco, told UPI biologic agents that block the inflammatory protein called tumor necrosis factor-alpha, or TNF-alpha, could prove more potent over time, because they do not inhibit immune system activity in any way.

One such agent, Enbrel, by Immunex Corp., of Seattle, already is approved for treating rheumatoid arthritis and psoriatic arthritis. Clinical trials indicated Enbrel injections curbed psoriasis symptoms by 75 percent or more in 49 percent of patients, and a lower dose had the same effect in 34 percent of patients. Most notable, response rates for Enbrel rose after six months of continuous treatment.

"Enbrel is likely to dominate the market," said Kantor, "simply because it has been around the longest and has the added factor of being, like insulin, an at-home injectable treatment." For some reason, however, Medicare will only reimburse for treatments given in a doctor's office, which could exclude reimbursement for Enbrel, he added.

Kantor said because Enbrel is FDA-approved for psoriatic arthritis, a closely-related condition, physicians are noting "a little bit of psoriatic arthritis" in their diagnosis and so they can be reimbursed for the $10,000-to-12,000-per-year treatments by private insurers. Enbrel is being widely-used for psoriasis in an "off-label" mode, he noted, which is how a U.S. physician can prescribe a drug for one condition even though its FDA approval was for another condition.

Kantor said although all of the biologics come with a high price tag, "the effects are so powerful that we don't see inhibitions in insurance reimbursements for those who take Amevive or Enbrel, the later with a psoriatic arthritis diagnosis involved."

Another rheumatoid arthritis agent, Remicade, by Centocor Inc., of Malvern, Pa., also is being studied for its potential use in psoriasis therapy. Remicade blocks the same inflammatory protein as Enbrel. A study of 249 patients with moderate-to-severe psoriasis showed 88 percent treated with a higher dose of Remicade achieved a 75 percent or greater improvement in symptoms after 10 weeks. Even at a lower dosage, 72 percent of the trial subjects achieved a 75 percent or greater improvement.

Kantor noted the annual market for biologic treatments for psoriasis in the U.S. alone could be worth $2 billion, with the market in Europe adding another $1 billion in potential sales. If biologic agents continue to show promise in treating other inflammatory conditions, he said, "then added to rheumatoid arthritic, psoriatic arthritis and psoriasis, the numbers could explode."

At present, Gaspari said, "There is no cure for any of the inflammatory diseases. As we unravel the mysteries of the immune system and identify genes that are passed on in families, we may be able to develop therapies that can cure these awful diseases. For now, the biologics are the advance guard of what we have to offer patients and their use appears to be growing to include many if not most of the major inflammatory diseases."

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