Arava (leflunomide) or methotrexate?

[Guest guest]

Noreen, I haven't " been there, " but I would like to offer some

information you may wish to consider while you are trying to decide

between Arava (leflunomide) and methotrexate (MTX).

First, both are DMARDs and have approximately the same level of

efficacy, although we don't really have much long-term comparison data

to work with since Arava is relatively new. Also, both have serious

possible side effects. At least a chest x-ray, if not pulmonary function

tests, should be performed before starting either drug.

MTX has been used for decades in oncology and rheumatology (approved for

use for psoriasis in 1971 and RA in 1988), and its effectiveness and

side-effect profile are well-known. Your physician will (or should) be

aware of what to look out for if you are on MTX.

Arava was approved by the FDA in September of 1998 and its side-effect

profile is still being developed. It has a long half-life (about 2

weeks) and can remain in the body's tissues for up to two years. There

is a washout procedure available if serious adverse effects develop.

In March 2002, Public Citizen petitioned the FDA to remove Arava from

the market, citing that it was no more effective than MTX and that the

rate of adverse reactions, some of which were fatalities, was much

higher. They stated:

" From when it was first marketed in late September 1998 through

September 2001, Arava has been associated with at least 130 severe

hepatic reactions including 56 hospitalizations and 22 deaths, two of

whom were patients in their twenties. For 12 of these deaths,

leflunomide-induced liver toxicity appears to be the most plausible

explanation. Similar serious reactions have caused the European Agency

for the Evaluation of Medicinal Products (EMEA) to issue an urgent

warning to patients and physicians concerning the potential causal

relationship of leflunomide to severe liver injury, including death.

...

In other words, there were approximately 5.5 times more prescriptions

filled for methotrexate than for leflunomide during this interval.

However, as shown in table 1, below, there were six times more reports

of fatal liver toxicity with leflunomide than with methotrexate (12 vs.

2), 13 times more reports of hypertension than for methotrexate (38 vs.

3) and, for the life-threatening autoimmune disease, s-

Syndrome, there were 12 cases with leflunomide and none with

methotrexate. For all of these serious adverse reactions, therefore, the

toxicity of leflunomide is clearly greater than that of methotrexate,

especially since there were 5.5 times more prescriptions filled for

methotrexate than for leflunomide during the interval. "

At a meeting on March 5, 2003, the FDA chose to keep Arava on the

market.

You can read the entire Public Citizen petition, the FDA Advisory

Committee decision, and related items here:

Petition to ban arthritis drug leflunomide (Arava)

HRG Publication #1614

http://www.citizen.org/documents/1614.pdf

Dr. S. Firestein's letter to the FDA regarding Public Citizen's

petition to ban Arava:

http://www.fda.gov/ohrms/dockets/dailys/02/Jun02/062102/02P-0139_emc-000001-01.d\

oc

Letter to FDA addressing Dr. Firestein's comments concerning HRG's

petition to remove ARAVA from the market

HRG Publication #1644

http://www.citizen.org/publications/release.cfm?ID=7212

FDAAdvisoryCommittee.com

" Aventis Arava Does Not Require Labeling Change To Increase Warning On

Liver Toxicity, Cmte. Says " :

http://www.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/Arthritis+D\

rugs/030503_Arava/030503_AravaR.htm

FDA Center for Drug Evaluation and Research

Arthritis Advisory Committee Meeting Transcript

March 5, 2003

http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3930T2.htm

Whichever drug you choose, ask lots of questions about these drugs of

your physician. Ask if your physician has a preference between the two.

Arava is taken orally and MTX is available in both oral and injectable

forms. If you decide to go with MTX, I'd use the injectable and ask

about supplementation with folic acid.

Good luck!

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

Re: [ ] Re: Methotrexate

> I really do need some advice on the " next step " for me. I just

contacted my rheumy, and she wants me to go on either methotrexate, or

Arava. So big question here, what are the advantages/side effects of

each, and which way would those of you who have been there would

recommend?

> Noreen