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Rheumatoid-Arthritis Drug Found

Scientists say: Used early, antibiotic relieves pain,

by n Neergaard

Associated Press

Rheumatoid-arthritis sufferers note: Scientists report that an antibiotic

used to treat acne significantly improves swollen, painful joints if therapy

begins in the crippling disease's early stages.

Rheumatologists said the new study by the University of Nebraska provides

enough proof of minocycline's benefit that the drug soon may be widely

prescribed.

" This isn't a cure, " cautioned the lead researcher, Dr. O'Dell, who

presented his study at a meeting of the American College of Rheumatology.

" If the medicine is stopped, the problem comes back. "

But O'Dell said the drug appears to offer a unique arthritis protection: It

seems to block enzymes, called metalloproteinases, that destroy

irreplaceable cartilage inside joints.

" By inhibiting these metalloproteinases early on, maybe we can help shut off

the whole inflammation cascade " that goes out of control in later stages of

the disease, O'Dell said.

If his theory is right, these enzymes also could have implications for

treatment of the much more common osteoarthritis that plagues the elderly.

Tests in osteoarthritic dogs suggest anti-enzyme compounds offer similar

protection, prompting other scientists to begin clinical trials of a

minocycline cousin - called doxycycline - in people with osteoarthritis.

About 2 million Americans suffer rheumatoid arthritis, a chronic

inflammatory disease. Unlike the osteoarthritis that hits certain joints

because of the wear-and-tear of aging, rheumatoid arthritis afflicts joints

all over the body. It often strikes women between the ages of 20 and 45.

Antibiotic therapy has been controversial. Doctors haven't proved, or

disproved, that an infection causes rheumatoid arthritis. And early studies

of minocycline showed only a modest effect, discouraging many physicians,

said Dr. Doyt Conn of The Arthritis Foundation.

Thinking earlier treatment might work better, O'Dell tested 46 patients who

had rheumatoid arthritis for less than a year and were not taking strong

arthritis medicines.

Sixty-five percent of the minocycline patients showed a 50% improvement in

joint swelling, stiffness and pain after six months of therapy. Just 13% of

patients given a dummy pill had a similar response.

How long improvement lasted was key, because many other treatments either

wear off or eventually cause serious side effects.

So O'Dell followed his patients for over three years - and 44% ultimately

improved by a dramatic 75% or more.

Such improvement over time is encouraging, said Dr. Schned, a

Minneapolis rheumatologist who has followed O'Dell's work.

Now doctors must study how best to combine minocycline with other common

medicines, he said.

Minocycline is old enough that not only are inexpensive generic forms

available, but doctors have had years to learn its side effects, Schned

said. " This is a safe and quite gentle medicine, " he said.

The main problem is dizziness among elderly patients, O'Dell said. About 5%

of long-term users develop dark splotches on the skin that disappear when

they stop the drug, he said.

If minocycline does work by blocking arthritis damage, it would join

research into such preventives:

- Drug companies Monsanto and Searle are developing a drug to block nitric

oxide, another chemical that destroys cartilage. Researchers will unveil the

first animal tests of the drug.

- Seattle-based Immunex reported that Phase III testing of its manmade

protein Enbrel reduced painful joints by a median of 71%. Enbrel mimics the

natural cell structure that captures tumor necrosis factor, a substance

important in inflammatory damage.

But TNF also can kill cancer cells, and rheumatologists cautioned that they

want longer-term studies to ensure that blocking the substance in arthritis

treatment is safe.

Using Antibiotics for the Treatment of Rheumatic Diseases - Some Questions

and Answers for Patients

1. What is antibiotic therapy for rheumatoid arthritis and how does it

differ from traditional treatments?

Antibiotic therapy utilizes low dose antibiotics, particularly those of the

tetracycline family, to attack the disease at its source. This therapy is

based on the belief that rheumatic disease is caused by an elusive organism

called a mycoplasma, similar in some ways to both a virus and bacterium, but

much smaller. The antibiotic can be taken in low dose fashion for months,

years, or even a lifetime in some cases without building up a tolerance to

the drug and without the serious side effects seen with conventional

medications.

Conventional therapy uses toxic medications and is aimed at controlling or

suppressing the symptoms. These medications, if they work at all, eventually

lose their effectiveness or become toxic, and patients find themselves worse

than before they started the medication.

2. Does this approach only work for rheumatoid arthritis?

No. We have scleroderma and lupus patients using only antibiotics who have

seen significant improvement, including reversal of symptoms and/or

remission. Dr. McPherson Brown, the Washington DC area rheumatologist

who pioneered this treatment some 50 years ago, also saw improvement in

cases of mixed connective tissue disease, ankylosing spondylitis,

dermatomyositis and polymyositis.

3. What dose is used and what is the cost?

Usually Minocin (minocycline) is the antibiotic of choice. It is prescribed

at very low dose, one or twice a day three days a week, usually Monday,

Wednesday, and Friday. The cost is approximately $2.50 per capsule,

depending on whether the generic or brand name of the drug is purchased.

Taking three tablets a week makes the cost about $7.50 a week. Larger

quantity drug purchases are cheaper. Ask your doctor to write your

prescription for larger quantities than 30 tablets, if it is a medication

you will be taking for a long time.

4. Can other antibiotics be substituted for Minocin?

Yes. Tetracycline and doxycycline are frequently substituted for Minocin and

both have proven to be effective. Tetracycline is the least expensive,

costing approximately 8 cents a tablet. Tetracycline is taken usually twice

a day, three days a week (M-W-F). It is more apt to react to foods and must

be taken on an empty stomach. Doxycycline is slightly more expensive. In

conjunction with the tetracycline family, clindamycin is frequently used as

a support therapy, either intravenously or oral.

5. Is there an advantage in using Minocin over the other antibiotics?

Yes. Bacterial cell membranes are surrounded by a lipid layer (a water

insoluble, fatty substance which surrounds the cell and provides it with

fuel). As a means of resisting antibiotics, the cells increase the thickness

of this lipid layer. Minocin has the best penetrating ability. It also has

an extended spectrum of activity and stays in the system longer and at

higher levels than tetracycline.

6. Are there side effects from using antibiotics?

Yes, as with all medications, there are possible side effects. Antibiotics

can cause yeast infections, especially in women. Minocin, however, seems to

have some anti-yeast activity. Some people experience a heightened

sensitivity to sunlight. Using a sunscreen can minimize this risk. In

children who have not yet cut their permanent teeth, tetracyclines can cause

staining of the teeth. Food can impair the absorption of some antibiotics

(not as true of doxycycline or minocycline) so they are to be taken on an

empty stomach. In people whose stomachs have become sensitized, nausea can

be a side effect. Tetracycline has an absorption rate of 50% when taken with

food. Minocin's absorption rate is 85% with food, making it a better choice

if food must be taken with the antibiotic. Diarrhea is another side effect

of antibiotics, and can be severe, but this side effect is rarely seen at

these doses, and is treatable if it occurs.

Correspondence:

The Road Back Foundation

4985 N. Lake Hill Road

Delaware, Ohio 43015-9249 USA