Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels

Abstract

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = − 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Clinical Pharmacology in Sarcoidosis: How to Use and Monitor Sarcoidosis Medications

“…LEF is a prodrug that is converted in the gut and liver to teriflunomide, its active form. This conversion is almost complete such that its original form of LEF is practically undetectable in the serum [ 74 , 75 ]. LEF’s pharmacologic effectiveness is achieved by the inhibition of dihydroorotate dehydrogenase (DHODH) in the de novo synthesis of pyrimidines.…”

Steps towards standard medical treatment of rheumatoid arthritis: A practical guide

“…In the case of contraindications to MTX therapy or early clinically significant intolerance to MTX, another csDMARD should be used, such as LEF at standard doses (usually 10-15 mg once daily) [15] or SSA at a target dose of 2-3 g/day. For LEF, the 10 mg dose is a therapeutic dose in most patients and adverse effects are more frequently observed with the 20 mg dose.…”

“…Contraindications to the receipt of adalimumab (and other TNF-a inhibitors) include [15]: hypersensitivity to an active ingredient or to any of the excipients; active tuberculosis or other severe infections such as sepsis and opportunistic infections; -moderate to severe heart failure -class III/IV according to New York Association Heart (NYHA) Classification. Adalimumab does not need dosage adjustment in elderly patients.…”