Precision Medicine Can Help Determine Response for Add-on Therapy

Plasma teriflunomide concentration and carriage of DHODH Haplotype 2 were associated with patient response upon adding leflunomide to existing disease-modifying drugs, according to a study published online in Arthritis Care & Research.

“Leflunomide is a commonly used disease-modifying drug in the treatment of rheumatoid arthritis,” researchers wrote. “Its effects are mediated via inhibition of dihydroorotate dehydrogenase (DHODH) by its active metabolite teriflunomide, and the pharmacokinetics of teriflunomide are highly variable.”
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The study included 67 patients with rheumatoid arthritis who were taking or were about to start added leflunomide after failing to achieve adequate response with conventional triple therapy. For each participant, researchers determined DHODH haplotype and collected up to five plasma samples after leflunomide was initiated to measure total and free teriflunomide concentrations. Disease activity for each patient was gauged using the 28-joint disease activity score (DAS28).

Patients who carried DHODH Haplotype 2 and not the shared epitope had higher disease activity after initiating leflunomide, according to the study. Disease activity lowered with total and free plasma teriflunomide concentration.

Teriflunomide concentrations above 16 mg/L were associated with a DAS28 that was 33% lower, researchers reported. When free teriflunomide concentration was above 35 µg/L, DAS28 was 32% lower.

“Teriflunomide concentration and carriage of DHODH Haplotype 2 are associated with response to leflunomide in patients with rheumatoid arthritis,” researchers wrote, “and a total plasma teriflunomide concentration of at least 16 mg/L is needed to maximize the likelihood of response.”

—Jolynn Tumolo

Reference

Wiese MD, Hopkins AM, King C, et al. Precision medicine with leflunomide: consideration of DHODH haplotype and plasma teriflunomide concentration can substantially modify outcomes in patients with rheumatoid arthritis [published online ahead of print Apr 27, 2020]. Arthritis Care Res. 2020;10.1002/acr.24236. doi:10.1002/acr.24236