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Predicting Methotrexate Response in Rheumatoid Arthritis Patients

CHANGES in DNA methylation at 4 weeks of methotrexate treatment for rheumatoid arthritis (RA) were associated with improvements in symptoms at 6 months, according to the results of a recent study. The finding suggests that this could be viewed as a biomarker, predicting future outcomes in this treatment pathway for patients.  

Dr Nisha Nair and colleagues, University of Manchester, Manchester, UK, examined DNA samples from the Rheumatoid Arthritis Medication Study (RAMS) which were collected at baseline and 4 weeks in patients whose response to methotrexate after 6 months, according to European League Against Rheumatism response criteria, was classified as ‘good’ (28-joint disease activity score [DAS28] 3.2/1.2-point improvement in DAS28 at 6 months) or ‘poor’ (DAS >5.1/improvement of 0.6 points at 6 months) (n=34 for both).  

Results indicated two differentially methylated positions in the 4-week samples from good and poor responders (p<1×10-6). Improvements at 6 months were also predicted by four cytosine-phosphate-guanine (CpG) sites: two linked increased methylation in good responders at 4 weeks with long-term swollen joint count improvement; two linked increased methylation at baseline and in good responders at 4 weeks with C-reactive protein improvement.  

The authors commented “The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of swollen joint count and C-reactive protein,” but added that the relapsing nature of RA as well as the lack of a control group were limiting factors to the study.