Genetic markers of treatment response in rheumatoid arthritis

Abstract

Rheumatoid arthritis patients exhibit a considerable interindividual variability in response to drug treatment. Although many disease-related and demographic factors have been studied to predict treatment outcome, the effective disease-modifying antirheumatic drug (DMARD) therapy is not yet allocated based on factors that predict efficacy. Individual genetic characteristics are thought to play an important role in treatment response; therefore, current research aims to identify these genetic predictors for clinical response. Pharmacogenetic studies are beginning to provide results, which suggests that personalized treatment maximization of DMARD efficacy and minimization of adverse drug reactions are feasible.

Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?

“…Regarding the 677C>T SNP, although some authors reported better or worse six-month responses in patients with CC [171,204] or TT [150] genotypes, respectively, and higher rates of remission in carriers of the T allele [205], a striking number of studies showed no association between 677C>T and MTX efficacy [152,166,188,189,195,206-215]. In a similar way, data for the 1298A>C SNP is also controversial: while some authors found better responses in 1298AA-positive patients compared to other genotypes [152,171,204], others, on the contrary, reported that C-allele carriers had lower MTX maintenance doses [208,209] and a non-significant tendency for higher remission rates [205]. Most studies failed to identify an association between this SNP and response to MTX [150,166,188,189,210-215].…”

Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype and methotrexate-induced adverse events in South Indian Tamil rheumatoid arthritis

“…The treatment response is influenced by several factors including differences in drug metabolism. Genetic factors may be responsible for up to 30 % of this difference [3]. The human multidrug resistance (MDR1) gene encodes for an integral membrane protein called P-glycoprotein which belongs to ATP-binding cassette (ABC) superfamily of transporters [4,5].…”

Optimalisation of the clinical pharmacogenetic model to predict methotrexate treatment response: the influence of the number of haplotypes of MTHFR 1298A–677C alleles on probability to respond

“…Several single nucleotide polymorphisms (SNP) have been reported to be associated with the efficacy of methotrexate in the treatment of rheumatoid arthritis (RA) 1 2. Subsequently, we developed a clinical model to predict the efficacy of methotrexate monotherapy in patients with recent-onset RA (N  =  205) 3.…”