Cardiovascular diseases (CVDs) lead to higher morbidity and mortality in rheumatoid arthritis; thus, we aimed to determine whether patients who had discontinued methotrexate treatment before the study enrollment (group MTX 0) were at a higher risk of CVD than patients treated with methotrexate at the time of the data collection (group MTX 1). A retrospective, prospective, observational, cross-sectional study was conducted. A total of 125 patients were enrolled in the study. Patients from the MTX 0 group (n = 35) were not treated with methotrexate for 7.54 (SD ± 4.21) years in average. Medical documentation as well as information taken in patient examinations during regular rheumatologist visits was used to obtain the required data. The composite of any CVD occurred less frequently in patients in the MTX 1 group than in the MTX 0 group (18.8 vs. 40.0%, OR 0.35, 95% CI, 0.15 to 0.83; p = 0.017) with a non-significant trend after adjustment for other treatments, which differed between study groups at the baseline (p = 0.054). Significant difference was found for the reduction of myocardial infarction in the MTX 1 group compared to the MTX 0 group (3.5 vs. 14.3%, OR 0.22, 95% CI, 0.05 to 0.97; p = 0.046). There were 4 deaths (4.7%) in the MTX 1 group as compared with 7 (20.0%) in the MTX 0 group (OR 0.20, 95% CI, 0.05 to 0.73; p = 0.015). Our results demonstrate that patients who discontinued methotrexate treatment are at a significantly higher risk of CVD and all-cause mortality. Based on our findings, we recommend stricter control of CVD in cases of methotrexate discontinuation.

• Keywords
• cardiovascular diseases, cardiovascular risk factors, methotrexate, methotrexate discontinuation, rheumatoid arthritis,
• Publication type
• Journal Article MeSH

We describe Caucasian monozygotic twin brothers with rheumatoid arthritis (RA) and discuss influence of predictors to methotrexate (MTX) outcome treatment. Single nucleotide polymorphisms (SNPs) of the MTX metabolic pathways were genotyped. Twins have multiple mutations: a CC mutation of SNP 1298A>C in methylenetetrahydrofolate reductase (MTHFR) gene, CC mutations of three SNPs in the adenosine receptor gene ADORA2A (rs3761422_4217241T>C, rs2267076_4221164T>C, rs2236624_4226593T>C), and a heterozygous genotype in SNPs ATIC_rs2372536_347C>G, MTHFD1_rs2236225_1958G>A. These mutations are known to predict a worse outcome of MTX treatment. The twins had different lifestyles (alcohol drinking and smoking in Twin 1, regular coffee consumption in Twin 2), but a very similar clinical presentation of the outset of RA, radiographic scoring according to the Sharp/van der Heijde method with an almost identical antibodies presentation. The period of the patients before anti-TNFα treatment was characterized by unsuccessful per oral MTX pharmacotherapy in both cases (a low effect of MTX in Twin 1; an early discontinuation of MTX due to an adverse event in Twin 2). In both twins, the outcome of well-controlled anti-TNFα treatment (co-medication with MTX in Twin 1) for 10 years was expressed as low disease activity measured using composite index DAS28. It is interesting that Twin 2 had an unfavorable radiographic scoring after a 10-year follow-up than Twin 1 in spite of the comparable DAS28 in Twin 2 and smoking in Twin 1. In conclusion, co-medication of MTX with biologics may impact on RA radiographic progression despite predicted bad MTX outcome based on pharmacogenetic analysis.

• Keywords
• methotrexate, pharmacogenetics, rheumatoid arthritis, twins,
• MeSH
• Antirheumatic Agents therapeutic use   MeSH
• White People genetics   MeSH
• Biological Products therapeutic use   MeSH
• Twins, Monozygotic MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Drug Therapy, Combination methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Disease Progression MeSH
• Arthritis, Rheumatoid drug therapy   genetics   pathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Letter MeSH
• Case Reports MeSH
• Names of Substances
• Antirheumatic Agents MeSH
• Biological Products MeSH
• Methotrexate MeSH