Genetic markers associated with clinical and radiographic response in adalimumab plus methotrexate-treated rheumatoid arthritis patients in OPTIMA

Biologics, including tumour necrosis factor inhibitors such as adalimumab (ADA), have significantly improved outcomes in rheumatoid arthritis (RA). Because the clinical course of RA and response to therapy may be influenced by the genetic background of the patient, the objective of this retrospective parallel-assigned case-control analysis was to evaluate the associations between candidate genetic markers for RA with clinical and radiographic responses to ADA + methotrexate (MTX) or MTX monotherapy in the Optimal Protocol for Treatment Initiation with MTX and ADA (OPTIMA) study.

Three candidate genetic markers were tested: HLA-DRB1 shared epitope (SE), interleukin 4 receptor (IL4R) single nucleotide polymorphism (SNP) rs1805010, and Fc gamma receptor IIb (FcgRIIb) SNP rs1050501. Genetic associations with week 26 clinical and radiographic responses during treatment with ADA + MTX or MTX monotherapy were assessed using summary statistics, chi-square or Fisher’s exact test, correlation, regression models, and corrected for multiple-comparisons.

Low disease activity (p=0.008) and improvement in American College of Rheumatology 20%, 50% and 70% response criteria (p=0.02, 0.01, and 0.02, respectively) were associated with HLA-DRB1 SE copy numbers in the ADA + MTX treatment arm, and the FcgRIIb SNP was a predictor of remission. The IL4R SNP correlated with radiographic progression in patients receiving MTX monotherapy, supporting previous findings.

This pharmacogenetic analysis identified genetic components that contribute to clinical responses to anti-rheumatic therapy.