Individualization of Leflunomide Dosing in Rheumatoid Arthritis Patients

Ashley M Hopkins; Catherine E O'Doherty; David JR Foster; Richard N Upton; Susanna M Proudman; Michael D Wiese

Personalized Medicine. 2014;11(4):449-461.

Background

Leflunomide is an immunomodulatory disease modifying anti-rheumatic drug (DMARD) that is most commonly used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis,^[1–8] and studies are also currently investigating its therapeutic potential in kidney transplant recipients with BK-virus nephropathy.^[9–11] The main aim of this review is to appraise the literature outlining the potential for dosage individualisation of leflunomide therapy in RA.

1 2 3 4 5 6 7 8 9 10

Next Section

Table 1. Pharmacogenetic effects on leflunomide pharmacokinetics, response and toxicity.
Designation	Effect	Ref.
CYP2C192* allele	Decreased teriflunomide concentrations	[37]
ABCG2 rs2231142 A allele	Increased teriflunomide concentration	[57]
DHODH rs3213422 C allele	Increased response; decreased toxicity	[54,58
DHODH haplotype 2	Decreased response	[56]
CYP1A2 rs762551 CC genotype	Increased toxicity	[53]
CYP2C19 poor and intermediate metaboliser phenotype	Increased toxicity	[55]
ESR1 rs2234693 TT genotype	Increased response	[59]
ESR1 rs9340799 AA genotype	Increased response	[59]