Indications for: ARAVA
Active rheumatoid arthritis.
The efficacy of Arava in the treatment of rheumatoid arthritis (RA) was evaluated in 3 controlled trials. In these trials, efficacy was evaluated by reduction of signs/symptoms (American College of Rheumatology [ACR] 20 Responder Index), inhibition of structural damage (Sharp Score), and improvement in physical function (Health Assessment Questionnaire and the Medical Outcomes Survey Short Form).
- 2-year study; 482 patients with active RA.
- Patients were randomly assigned to Arava 20mg/day (n=182), methotrexate 7.5mg/week increasing to 15mg/week (n=182), or placebo (n=118).
- Primary analysis was at 52 weeks with blinded treatment to 104 weeks.
- Arava was statistically significantly superior to placebo in reducing signs/symptoms of RA (% ACR20 responder) at the primary 12 month endpoint (P<.0001).
- No consistent differences were observed between Arava and methotrexate.
- Patients were randomly assigned to Arava 20mg/day (n=133), sulfasalazine 2g/day (n=133), or placebo (n=92); treatment duration: 24 weeks.
- Arava was statistically significantly superior to placebo in reducing signs/symptoms of RA (% ACR20 responder) at the 6 month endpoint (P =.0026).
- No consistent differences were observed between Arava and sulfasalazine.
- Patients were randomly assigned to Arava 20mg/day (n=501) or methotrexate 7.5mg/week increasing to 15mg/week (n=498); treatment duration was 52 weeks.
- No consistent differences were demonstrated between Arava and methotrexate.
ACR Responder rates at 12 months were maintained over 2 years in most patients continuing a second year of treatment.
Arava was statistically significantly superior to placebo in inhibiting the progression of disease by the Sharp Score. No consistent differences were demonstrated between Arava and methotrexate or between Arava and sulfasalazine.
Arava was statistically significantly superior to placebo in improving physical function. The improvement in physical function demonstrated at 6 and 12 months was maintained over 2 years.
Arava-associated hepatotoxicity and myelosuppression (low-risk): give loading dose of 100mg once daily for 3 days; then 20mg daily thereafter; (high-risk): give 20mg once daily without loading dose. Max 20mg/day. If not well tolerated, consider reducing to 10mg daily; monitor closely. Perform accelerated drug elimination procedure with cholestyramine and/or activated charcoal after stopping therapy.
Severe hepatic impairment. Concomitant teriflunomide. Pregnancy.
Embryo-fetal toxicity. Hepatotoxicity.
Pre-existing hepatic disease or ALT>2xULN: not recommended. Monitor liver function (esp. ALT) and blood (WBCs, platelets, hemoglobin, HCT) at baseline, then monthly for 1st six months; then every 6–8 weeks. If ALT elevations >3xULN, interrupt and evaluate; if likely leflunomide-induced, perform accelerated drug elimination procedure and monitor LFTs weekly until normalized; if unlikely, may consider resuming therapy. Obtain (–) pregnancy test before starting therapy. Females of reproductive potential should use effective contraception during treatment and during an accelerated drug elimination procedure after stopping treatment (see full labeling). Test and treat, if positive for active or latent TB infection prior to starting therapy. Renal impairment. Monitor BP. Severe immunodeficiency, bone marrow dysplasia, severe uncontrolled infections, nursing mothers: not recommended.
DMARD (pyrimidine synthesis inhibitor).
See Contraindications. Concomitant methotrexate, other immunosuppressants: monitor for hepatic or hematologic toxicity monthly. Caution with rifampin, and with other hepatotoxic drugs. May potentiate CYP2C8 (eg, paclitaxel, pioglitazone, repaglinide) or OAT3 (eg, cefaclor, cimetidine, ciprofloxacin) substrates, oral contraceptives; monitor and adjust dose as needed. May antagonize CYP1A2 (eg, alosetron, duloxetine, theophylline) substrates; monitor and adjust dose as needed. Consider reducing dose of OATP or BCRP substrates, esp. statins (limit rosuvastatin dose to 10mg/day). Concomitant live vaccines: not recommended; consider leflunomide long half-life before vaccination after stopping therapy. Monitor warfarin.
Diarrhea, elevated liver enzymes, alopecia, rash, respiratory infection, hypertension, headache, GI upset; rare: hepatotoxicity (may be fatal), interstitial lung disease, immunosuppression (possible sepsis), bone marrow suppression, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, peripheral neuropathy: stop therapy and perform drug elimination procedure.
Teriflunomide has a median half-life of 18-19 days. Without an accelerated drug elimination procedure, it may take up to 2 years to reach plasma teriflunomide concentrations of <0.02mg/L.
Teriflunomide is eliminated by direct biliary excretion as well as renal excretion.
Generic Drug Availability:
Tabs 10mg, 20mg—30; 100mg—blister pack (1 x 3)