Off-label drug use in rheumatoid arthritis

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Arthritis Foundation

Arthritis Today

March - April 2000

On Call: Medical Questions and Answers

" Off-Label Drug Use

Q. I have severe rheumatoid arthritis (RA) with vasculitis that hasn't

been helped by any of the drugs I have taken. My doctor wants me to take

a cancer drug called Cytoxan. Why would he prescribe a cancer drug for

RA? Can he do that legally?

A. You're right that Cytoxan (cyclophosphamide) is a cancer drug. It is

approved by the FDA for the treatment of several types of lymphoma,

leukemia and other cancers.

Even though it is not approved for RA, studies and clinical practice

have shown it to be helpful against RA-associated vasculitis

(inflammation of the blood vessels), so rheumatologists prescribe it for

that purpose.

Once a drug is approved to treat one condition, a doctor may prescribe

it for other diseases as he sees fit. This practice is called off-label

prescribing and it is commonly done.

In fact, some of the most successful drugs for arthritis-related

diseases were first prescribed off-label, because they were originally

developed and/or approved for other diseases. For example, methotrexate,

one of the most effective RA treatments, was originally developed and

approved as a cancer treatment. Doctors prescribed it off-label for RA

for many years before its manufacturer sought and received FDA approval

for RA.

But methotrexate is not the only arthritis drug that was first approved

for another condition. Here are some of the others:

Sulfasalazine (Azulfidine), was first approved for

inflammatory

bowel disease. It wasn't approved for RA until almost 50 years after its

development.

Cyclosporine (Sandimmune, Neoral), which was developed and

used to

prevent the rejection of transplanted organs, has in recent years been

approved for the treatment of rheumatoid arthritis and psoriasis.

Chloroquine was first used during World War II to treat

malaria.

Today, the chloroquine derivative hydroxychloroquine (Plaquenil) is

approved for both RA and lupus.

Infliximab (Remicade), was approved for Crohn's disease in

1998.

It was approved for RA last November.

Sometimes drugs begin to gain acceptance for off-label use purely by

coincidence. For example, in the 1940s while using chloroquine to treat

malaria patients, doctors noticed that patients who also had RA

experienced improvement in their RA symptoms. In other cases,

researchers have seen a similar mechanism between two diseases and

decided to try a drug that's already approved for one condition to treat

the other.

The FDA does not prohibit the practice of off-label prescribing;

however, it does regulate the claims a drug company can make about a

drug and the diseases for which the company can market a drug. That is,

a drug company cannot market - either through advertisements or

one-on-one discussions with doctors - a drug for conditions other than

those for which the drug is FDA approved.

Once clinical practice suggests that an off-label use is successful,

controlled studies should be - but are not always - done to demonstrate

the drug's benefit. If studies confirm that a drug is useful for a

condition other than the one(s) for which it is approved, its

manufacturer may choose to pursue FDA approval for the other disease as

well.

This process helps determine optimal dosages and ensure the

effectiveness of drugs for the disease conditions for which they're

prescribed. So far the maker of Cytoxan has not submitted it for FDA

approval as an RA drug.

No matter which drug your doctor prescribes - off-label or not - it's

important that you know how to take the drug properly, recognize

potential side effects, and know what to do if you experience side

effects.

Doyt L. Conn, MD, Rheumatologist "

http://www.arthritis.org/resources/arthritistoday/2000_archives/2000_03_04_on_ca\

ll.asp

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org