Table III.
Initial and final models for the Cox regression of predictors of time-to-significant adverse event (SigAE).
| Initial Model |
Final Model |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | HR* | 95% CI | p-value | HR | 95% CI | p-value | |||
| Age | 1.00 | 0.98 | 1.01 | 0.750 | |||||
| Gender | 0.96 | 0.42 | 2.20 | 0.919 | |||||
| Caucasian | 0.88 | 0.49 | 1.56 | 0.655 | |||||
| RF positive | 0.98 | 0.53 | 1.82 | 0.955 | |||||
| ACPA positive | 0.96 | 0.53 | 1.74 | 0.890 | |||||
| Tobacco use | 1.25 | 0.90 | 1.72 | 0.185 | |||||
| Yrs RA dx and MTX | 1.00 | 1.00 | 1.00 | 0.571 | |||||
| MTX first DMARD | 0.72 | 0.38 | 1.38 | 0.328 | |||||
| Deyo Index | 1.06 | 0.97 | 1.16 | 0.221 | |||||
| Glucocorticoid use | 2.07 | 1.16 | 3.69 | 0.014 | 2.28 | 1.16 | 4.49 | 0.017 | |
| Avg. DAS-28 | 1.09 | 0.90 | 1.32 | 0.389 | |||||
| HLA-DRB1-SE | 1.16 | 0.90 | 1.49 | 0.253 | |||||
| MTHFR, rs1801131 | Homo major (AA) | 1.72 | 1.25 | 2.38 | 0.001 | ref. | |||
| Het (AC) | 3.05 | 1.48 | 6.29 | 0.003 | |||||
| Homo minor (CC) | 3.88 | 1.62 | 9.28 | 0.002 | |||||
| MTHFR, rs1801133 | 0.80 | 0.54 | 1.19 | 0.272 | |||||
| FPGS, rs7033913 | Homo major (TT) | 1.35 | 0.93 | 1.94 | 0.112 | ref. | |||
| Het (TC) | 0.99 | 0.39 | 2.48 | 0.976 | |||||
| Homo minor (CC) | 0.38 | 0.04 | 3.54 | 0.393 | |||||
| FPGS, rs10760503 | 0.87 | 0.61 | 1.24 | 0.444 | |||||
| FPGS, rs10106 | 0.80 | 0.56 | 1.15 | 0.232 | |||||
| GGH, rs12548933 | 1.30 | 0.91 | 1.85 | 0.149 | |||||
| GGH, rs7010484 | 1.07 | 0.74 | 1.56 | 0.708 | |||||
| GGH, rs4617146 | 0.95 | 0.60 | 1.50 | 0.834 | |||||
| GGH, rs719235 | 0.84 | 0.56 | 1.27 | 0.409 | |||||
| GGH, rs11988534 | Homo major (CC) | 1.30 | 0.97 | 1.74 | 0.083 | ref. | |||
| Het (CT) | 0.74 | 0.15 | 3.61 | 0.712 | |||||
| Homo minor (TT) | 1.78 | 0.42 | 7.51 | 0.430 | |||||
| rs7033913*rs11988534 | Homo major/ Homo major | ref. | |||||||
| Het/Het | 3.22 | 0.54 | 19.33 | 0.201 | |||||
| Het/Homo minor | 1.29 e−17 | 1.88 e−18 | 8.81 e−17 | <0.001 | |||||
| Homo minor/ Het | 22.21 | 1.47 | 336.80 | 0.025 | |||||
| Homo minor/ Homo minor | 4.74 | 0.32 | 70.76 | 0.259 | |||||
HR: hazard ratio; Std. Err.: standard error; 95% CI: 95% confidence interval; RF: rheumatoid factor; ACPA: anti-cittrulinated protein antibody; RA: rheumatoid arthritis; Yrs RA dx and MTX: years between rheumatoid arthritis diagnosis and methotrexate course; MTX: methotrexate; DMARD: disease-modifying anti-rheumatic drug; DAS-28: 28 joined 4-variable disease activity score; HLA-DRB1-SE: major histocompatibility complex, class II, DR beta 1 shared epitope; ref: referent; MTHFR: methylenetetrahydrofolate reductase; FPGS: folypoly-gamma-glutamate synthetase; GGH: gamma-glutamyl hydrolase; ACPA: anti-citrullinated protein antibody; Homo: homozygous; Het: heterozygous; rs7033913 *rs11988534: interaction term between FPGS rs7033913 & GGH rs11988534.