EP28 Adenosine deaminase-genetic polymorphism and baseline serum level as a biomarker of treatment response to methotrexate in rheumatoid arthritis

Abstract

Abstract Background Despite methotrexate (MTX) being the first line therapy for RA,30% of patients do not respond to MTX. Methotrexate acts by increasing adenosine levels which lead to anti-inflammatory effects. Adenosine deaminase (ADA) enzyme converts adenosine to inosine thus reduces levels of adenosine. Thus, ADA levels and single nucleotide polymorphism (SNP) in ADA gene may affect the treatment effect of MTX. Our objective was to study if genetic polymorphism in ADA gene and baseline serum ADA levels in patients with RA is associated with methotrexate response. Methods 207 DMARD naïve active RA (DAS28 ESR ≥3.2) patients satisfying EULAR/ACR 2010 criteria were enrolled. Genotyping was done in all patients (n = 207) by TaqMan 5' nuclease assay. In a subset of patients(n = 59) blood sample was collected at baseline and 2 months for ADA estimation by ELISA. Ethical approval and written informed consent was taken. Oral MTX was initiated at dose of 15mg/week, escalated 5mg every month till the patients had DAS28 < 2.6 or a maximum dose of 25 mg/week was reached. At 4 months based on EULAR response patients were classified as responders or non-responders. Using a Chi-squared test, SNPs were associated with response to methotrexate therapy. Baseline clinical parameters and serum ADA levels were correlated with EULAR response. Results Among 207 patients (177females) mean age was 41.49± 12.14 years and median disease duration 24 (40) months.172 patients (83.1%) were responders and 35 (16.9%) non-responders. 197 (95.16%) patients were seropositive (RF and/or ACCP+). With regard to SNP in ADA gene,47.8% were AA,42.5% AG and 9.7% were GG genotype. Mean DAS 28 CRP was 4.76 ± 1.05 and median DAS 28 ESR was 6.00 (1.38). Mean serum baseline ADA was 10.82 ±5.33 pg/dl. Except DAS28ESR (p = 0.02), other baseline parameters like age, disease duration, ESR, CRP, DAS 28 CRP were similar between responders and non-responders. SNPs in ADA gene were not associated with EULAR response (p = 0.475). Baseline ADA levels (10.52 ± 5.37 vs 12.28 ± 5.14; p = 0.34) 2 month ADA levels (p = 0.34) and change in ADA level from baseline at 2 months, i.e. delta ADA (p = 0.55) did not show any association with MTX response. Mean ADA level was similar between the 3 genotypes of ADA(p = 0.736) Comparison of parameters between methotrexate responders and non-responders Conclusion ADA gene polymorphism and serum ADA levels do not affect response to methotrexate. Disclosures H. Gangadharan Nair: Grants/research support; Indian Rheumatology Association Research grant. A. Singh: None. S. Majumder None. A. Aggarwal None.