Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis

Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment

“…This report confirms that almost one third of patients affected by rheumatoid arthritis do not respond to low-dose MTX treatment [15-18]. This phenomenon causes that the discovery of (bio)markers of response to the drug is still required for clinical practice.…”

“…MTX as a foliate antagonist is used in therapy of malignant disorders, but also suppresses the immune response in patients and in low doses was introduced for the treatment of RA because of its presumed anti-proliferative, immunosuppressive and anti-inflammatory properties [14]. However, MTX is not sufficient in all RA patients, and approximately 50-60% of RA patients could be classified as MTX responders [15-18]. It seems that the effectiveness of MTX treatment corresponds to the individual genetic background, particularly in genes encoding key molecules of methotrexate metabolism and toxicity [19,20].…”

MDR1 in immunity: friend or foe?

“…Despite contradictory data in the literature, MTX is not a substrate of MDR1 but of MRP1. 81 Under MTX treatment, MDR1 expression might therefore not be a resistance factor but rather reflect disease activity. 82 Strategies combining drugs that are not substrates of MDR1 (e.g., MTX, infliximab) with MDR1 inhibition by tacrolimus partially restored response to treatment in refractory RA patients and decrease MDR1 expression on both T and B lymphocytes.…”

Association of HLA-E*01:01/*01:03 polymorphism with methotrexate-based treatment response in South Indian rheumatoid arthritis patients

“…sex, age at onset, disease activity and functional impairment, autoantibody status (RF, ACPA) and cytokine profile at baseline (TNFa, IL1ra/IL1b) influence the outcome of treatment but are poor predictors of treatment response. 28,29 This has led to i n d i a n j o u r n a l o f r h e u m a t o l o g y 9 ( 2 0 1 4 ) 1 7 8 e1 8 3 efforts to identify relevant biomarkers for therapeutic response in RA. There is conflicting data on the influence of genes on treatment response.…”