Health Boards
Objective:
To determine the “real-world” clinical effectiveness and safety of leflunomide (Arava) in patients with psoriatic arthritis (PsA).
Methods:
This prospective, multinational 24-week observational study involved adult patients with active PsA who initiated treatment with leflunomide.Patients were evaluated at baseline, 12 weeks, and 24 weeks.The primary outcome was response as assessed by Psoriatic Arthritis Response Criteria (PsARC) in patients with pre- and post-treatment data.A modified PsARC response analysis included patients with joint counts, but no severity scores.Other effectivenessevaluations included global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions.All patients were evaluated for safety.
Results:
A total of 514 patients were enrolled in this study (mean age, 50.7 years; mean disease duration,6.1 years). In the primary effectivenessanalysis, 380 of 440patients (86.4%; 95% confidence interval 82.8% – 89.4%) achieved a PsARC response at 24 weeks. Significant improvements were observed in tender and swollen joint scores and counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions.The discontinuation rate was 12.3%.Ninety-eight adverse drug reactions occurred in 62 (12.1%) patients; 3 were serious (2 increased liver enzymes, 1 hypertensive crisis).
Conclusion:
Leflunomide is an effective and well tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease. © 2012 by the American College of Rheumatology
Source: onlinelibrary.wiley.com
Arava is a trade name of the drug leflunomide.
Notes:
Females of childbearing potential
Do not start Arava® until the following steps are completed:
Pregnancy is excluded.
Confirm that reliable contraception is being used.
Fully counsel patients on the potential for serious risk to the fetus.
If the patient becomes pregnant while taking this drug, the physician and patient must discuss the risk to the pregnancy.
Upon discontinuation of Arava®, it is recommended that all females of childbearing potential undergo the drug elimination procedure.
Females on Arava® who wish to become pregnant
Must discontinue Arava® and undergo the drug elimination procedure.
Human plasma levels of the active metabolite less than 0.02 mg/L (0.02 µg/mL) are expected to have minimal risk based on available animal data.
Drug elimination procedure for females
Administer cholestyramine 8 grams 3 times daily for 11 days. (The 11 days do not need to be consecutive unless there is a need to lower the plasma level rapidly.)
Verify plasma levels less than 0.02 mg/L (0.02 µg/mL) by 2 separate tests at least 14 days apart. If plasma levels are higher than 0.02 mg/L, additional cholestyramine treatment should be considered.
Without the drug elimination procedure, it may take up to 2 years for the active metabolite of leflunomide to reach plasma levels less than 0.02 mg/L due to individual variation in drug clearance.
Information for males
Available information does not suggest that Arava® would be associated with an increased risk of male-mediated fetal toxicity. To minimize any possible risk, men wishing to father a child should consider discontinuing use of Arava® and taking cholestyramine 8 grams 3 times daily for 11 days.
Additional safety information
Arava® is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. Severe infections including sepsis, which may be fatal, have been reported. Rarely, interstitial lung disease, which may be fatal, has been reported.
Rare reports of pancytopenia, agranulocytosis, thrombocytopenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis, and peripheral neuropathy have been reported in post marketing experience. In these or any other serious toxicities, Arava® should be stopped and a drug elimination procedure (eg, cholestyramine 8 g TID x 11 days) should be used to reduce the drug concentration more rapidly.
It would be prudent to monitor for hematologic toxicity when switching from Arava® to another antirheumatic agent with a known potential for hematologic suppression.
Adverse reactions associated with the use of Arava® in clinical trials at 1 year (n=1339) included diarrhea (17%), respiratory infection (15%), alopecia (10%), hypertension (10%), rash (10%), and elevated liver enzymes (ALT and AST) (5%)
Laboratory tests
At minimum, ALT (SGPT) must be performed at baseline and at least monthly for six months after starting ARAVA, and thereafter every 6 to 8 weeks.
At minimum, patients taking Arava® should have platelet, white blood cell count, and hemoglobin or hematocrit monitored at baseline and monthly for 6 months following initiation of therapy and every 6 to 8 weeks thereafter.
If used concomitantly with immunosuppressants such as methotrexate, chronic monitoring should be monthly.
To determine the “real-world” clinical effectiveness and safety of leflunomide (Arava) in patients with psoriatic arthritis (PsA).
Methods:
This prospective, multinational 24-week observational study involved adult patients with active PsA who initiated treatment with leflunomide.Patients were evaluated at baseline, 12 weeks, and 24 weeks.The primary outcome was response as assessed by Psoriatic Arthritis Response Criteria (PsARC) in patients with pre- and post-treatment data.A modified PsARC response analysis included patients with joint counts, but no severity scores.Other effectivenessevaluations included global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions.All patients were evaluated for safety.
Results:
A total of 514 patients were enrolled in this study (mean age, 50.7 years; mean disease duration,6.1 years). In the primary effectivenessanalysis, 380 of 440patients (86.4%; 95% confidence interval 82.8% – 89.4%) achieved a PsARC response at 24 weeks. Significant improvements were observed in tender and swollen joint scores and counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions.The discontinuation rate was 12.3%.Ninety-eight adverse drug reactions occurred in 62 (12.1%) patients; 3 were serious (2 increased liver enzymes, 1 hypertensive crisis).
Conclusion:
Leflunomide is an effective and well tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease. © 2012 by the American College of Rheumatology
Source: onlinelibrary.wiley.com
Arava is a trade name of the drug leflunomide.
Notes:
Females of childbearing potential
Do not start Arava® until the following steps are completed:
Pregnancy is excluded.
Confirm that reliable contraception is being used.
Fully counsel patients on the potential for serious risk to the fetus.
If the patient becomes pregnant while taking this drug, the physician and patient must discuss the risk to the pregnancy.
Upon discontinuation of Arava®, it is recommended that all females of childbearing potential undergo the drug elimination procedure.
Females on Arava® who wish to become pregnant
Must discontinue Arava® and undergo the drug elimination procedure.
Human plasma levels of the active metabolite less than 0.02 mg/L (0.02 µg/mL) are expected to have minimal risk based on available animal data.
Drug elimination procedure for females
Administer cholestyramine 8 grams 3 times daily for 11 days. (The 11 days do not need to be consecutive unless there is a need to lower the plasma level rapidly.)
Verify plasma levels less than 0.02 mg/L (0.02 µg/mL) by 2 separate tests at least 14 days apart. If plasma levels are higher than 0.02 mg/L, additional cholestyramine treatment should be considered.
Without the drug elimination procedure, it may take up to 2 years for the active metabolite of leflunomide to reach plasma levels less than 0.02 mg/L due to individual variation in drug clearance.
Information for males
Available information does not suggest that Arava® would be associated with an increased risk of male-mediated fetal toxicity. To minimize any possible risk, men wishing to father a child should consider discontinuing use of Arava® and taking cholestyramine 8 grams 3 times daily for 11 days.
Additional safety information
Arava® is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. Severe infections including sepsis, which may be fatal, have been reported. Rarely, interstitial lung disease, which may be fatal, has been reported.
Rare reports of pancytopenia, agranulocytosis, thrombocytopenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis, and peripheral neuropathy have been reported in post marketing experience. In these or any other serious toxicities, Arava® should be stopped and a drug elimination procedure (eg, cholestyramine 8 g TID x 11 days) should be used to reduce the drug concentration more rapidly.
It would be prudent to monitor for hematologic toxicity when switching from Arava® to another antirheumatic agent with a known potential for hematologic suppression.
Adverse reactions associated with the use of Arava® in clinical trials at 1 year (n=1339) included diarrhea (17%), respiratory infection (15%), alopecia (10%), hypertension (10%), rash (10%), and elevated liver enzymes (ALT and AST) (5%)
Laboratory tests
At minimum, ALT (SGPT) must be performed at baseline and at least monthly for six months after starting ARAVA, and thereafter every 6 to 8 weeks.
At minimum, patients taking Arava® should have platelet, white blood cell count, and hemoglobin or hematocrit monitored at baseline and monthly for 6 months following initiation of therapy and every 6 to 8 weeks thereafter.
If used concomitantly with immunosuppressants such as methotrexate, chronic monitoring should be monthly.