In clinical studies involving more than 1,800 patients world-wide, Arava was shown to be effective as a therapy for long-term
use. "The data,as evidenced by x-ray,clearly showed that Arava slows disease progression"said Dr. Bourgouin.
Arava was generally well tolerated in these studies with the most common transient side effects being diarrhea,elevated
liver enzymes,hair loss, and rash.
In a one-year,phase III,placebo-controlled trial,482 patients were given one of 3 treatments. Arava 20mg/day after a
loading dose of 100 mg/day for 3 days, placebo (with an increase to 15 mg/week for continued active disease.
Sixty % of the MTX patients were increased to 15 mg/week during weeks seven through nine. The efficacy and safety of
Arava at the one-year primary end-point was presented at the ACR last year.
In a second year continuation of the trial to look for maintained effect at 2 years,MTX dose could be increased as high
as 20mg/week. 235 patients continued for the second year of therapy (Arava was compared only to MTX because of the predictably
small number of patients continuing on placebo).
"The data showed that clinical and radiographic improvement observed with Arava and MTX at one year was maintained at
two years,providing evidence of the durability and consistency of Arava efficacy and safety"said Dr Vibele Strand,clinical
associate professor at Stanford University.
"Additionally,at two years,Arava DEMONSTRATED STATISCALLY SIGNIFICANTLY IMPROVEMENTS IN ACR 20 RESPONSE rates compared
to the active control,Methotrexate Disease progression was stabilized with both Arava and MTX at 2 years".
In the same study improvement in physical function with Arava remained consistent over 2 years.Improvement was statiscally
significant compared to methotrexate.
This improvement was assessed through a series of validated questionnaires designed to measure patients' functional ability
in terms of their ability to conduct daily activities (e.g.,walking,eating,dressing,washing) and their function in daily life.
These questionnaires included the Health Assessment Questionnaire (HAQ) and the Problem Elicitation Technique (PET).
In a separate scientific analysis presented at ACR,Arava was assessed to determine the consistency of its effect for
slowing RA disease progression. Results from three large mutinational, controlled trials were compared and analyzed.
Arava consistently retarded the structural damage across all three clinical trials regardless of patient disease duration.
The treatment effect was observed at both 6 months and at one year.
Pregnancy must be excluded before the start of treatment with Arava. Arava is contraindicated in pregnant women or women
of child-bearing potential who are not using reliable contraception. Before using Arava patients must be fully counseled on
the potential for serious risks to the fetus.
Pregnancy must be avoided during Aravaa treatment or prior to the completion of a drug elimination procedure with
cholestyramine after Arava treatment. It is recommended that all women of child bearing potential undergo this elimination
procedure upon discontinuing Arava as the drug may increase the risk of fetal death or teratogenic effects when administered
to a pregnant women.
In addition men wanting to father a child should consider discontinuing Arava and taking cholestyramine eight grams
three times daily for 11 days to minimize any possible risk to the fetus.
Arava was associated with elevations in liver enzymes,primarily ALT and AST,in a significant number of patients in clinical
trials' Although these effects were generally reversible with dose reduction or discontinuation of treatment,marked elevation
(greater than3 times the upper limit of normal) occurred as well.
Therfore,at minimum.ALT levels should be measured at the beginning of therapy (baseline) and monitored initially at monthly
intervals, then,if stable, at intervals determined by the individual clinical situation. Arava is not recommended in patients
with significant hepatic impairement or positive hepatitis B or C serologies given the risk of increased hepatoxicity.
Adverse reactions associated with the use of Arava include diarrhea,elevated liver enzymes (ALT and AST),alopecia,and
rash. The higher incidence of liver toxicity and the resulting death of 130 patients world-wide have prompted the public advocacy
group,"Public Citizen" to ask the FDA to investigate the concern further,and requested a ban on the drug..
The FDA said further studies will be conducted with respect to this concern but no immediate action is contemplated.
Arava officials have indicated they are unaware of any extra-ordinary concern related to the medication in general.
Arava have recently,been tried on certain J.R.A. patients with a positive clinical trial result. This is important as
some JRA patients are not tolerant to MTX therapy.
Arava reduces inflammation by suppressing the immune cells responsible for the inflammation. It does this by preventing
the formation of DNA and RNA in the immune cells by inhibiting an enzyme (dihydroorotate dehydrogenase --DHODH) that is necessary
for the production of a critical component of DNA and RNA,pyrimidine (nucleic acid).--it is thought,it suppresses the formation
of rapidly dividing cells from forming.
Arava may be more suitable for patients who are intolerant to or failed MTX therapy. I personally tried Arava 20
mg./daily (without MTX) and it did not help me. MTX (22.5 mg./weekly) did aid my RA. Drug efficacy is different for each
patient. Some patients will fail Arava,Enbrel or Remicade and work wonders for others.
Recent reports about 13 deaths world-wide attributed to patients taking Arava,and liver toxicity originated from
an European web site. Those patients affected had a pre-existing liver disease,and/or were on other hepatotoxic drugs
as well as Arava.
Even the advocacy group,"Public Citizen" got involved, and petitioned the FDA to conduct a study,and they made
a further request to ban the drug. (Actual facts will show the reports biased,and not fully explained in the articles). The
ACR website addresses the concern.