Table 2. Prevalencey, univariable OR’s (95% CI) for potential predictors of 3 months DAS28>3.2 insufficient response for derivation and validation cohorts.
| Predictors | Derivation cohort | Validation cohort | |||
|---|---|---|---|---|---|
| n (%) | OR (95% CI) | n (%) | OR (95% CI) | ||
| Female | 201 (71) | 1.70 (0.99–2.91)* | 72 (71) | 2.29 (0.80–6.59)* | |
| Age > 40 year | 239 (84) | 1.76 (0.89–3.50)* | 78 (77) | 1.44 (0.49–4.28) | |
| Medication | |||||
| No HCQ | 98 (38) | 1.47 (0.87–2.48)* | 53 (53) | 1.05 (0.43–2.54) | |
| No Sulfasalazine | 99 (38) | 1.42 (0.84–2.40)* | 59 (58) | 1.51 (0.61–3.77) | |
| No TDT | 99 (38) | 1.42 (0.84–2.40)* | 69 (68) | 1.24 (0.47–3.26) | |
| GC | 242 (93) | 1.68 (0.56–4.98) | 14 (14) | 2.22 (0.55–8.98) | |
| No IM-GC | 160 (62) | 1.42 (0.82–2.46) | 11 (11) | 0.61 (0.04–10.07) | |
| NSAID | 37 (14) | 1.53 (0.69–3.41) | 36 (36) | 1.69 (0.67–4.26) | |
| SNPs (MAF) | |||||
| ABCB1 rs1045642 G>A (A = 0.3952) | AA vs GG/GA | 190 (73) | 1.77 (0.99–3.18)* | 64 (67) | 2.08 (0.71–6.06)* |
| ABCB1 rs1128503 G>A (A = 0.4161) | AA vs GG/GA | 217 (83) | 1.49 (0.76–2.95) | 73 (77) | 1.21 (0.37–3.93) |
| ABCB1 rs2032582 C>A/T (A = 0.3343) | AA/AT/TT vs CC/CA/CT | 208 (79) | 1.70 (0.90–3.22)* | 72 (76) | 0.96 (0.31–2.97) |
| ABCC1 rs35592 T>C (C = 0.3704) | TC/CC vs TT | 163 (62) | 1.05 (0.63–1.75) | 55 (58) | 0.95 (0.37–2.43) |
| ABCC1 rs3784862 A>G (G = 0.4155) | AG/GG vs AA | 153 (58) | 1.05 (0.63–1.75) | 43 (45) | 0.52 (0.20–1.36)* |
| ABCC2 rs717620 C>T (T = 0.1350) | CC vs CT/TT | 74 (28) | 1.30 (0.75–2.25) | 30 (32) | 0.77 (0.28–2.11) |
| ABCC2 rs4148396 C>T (T = 0.3147) | CC/CT vs TT | 35 (13) | 1.46 (0.71–3.01) | 10 (11) | 1.47 (0.30–7.10) |
| ABCC3 rs3785911 A>C (C = 0.2452) | AC/CC vs AA | 134 (51) | 1.28 (0.78–2.11) | 45 (47) | 1.41 (0.55–3.59) |
| ABCC3 rs4793665 T>C (C = 0.3313) | TT vs TC/CC | 173 (66) | 2.02 (1.17–3.49)* | 68 (72) | 0.36 (0.13–1.00)* |
| ABCC4 rs868853 T>C (C = 0.1757) | TT vs TC/CC | 38 (14) | 1.21 (0.60–2.45) | 20 (21) | 1.53 (0.53–4.43) |
| ABCC4 rs2274407 C>A (A = 0.1506) | CA/AA vs CC | 232 (88) | 1.09 (0.50–2.38) | 81 (85) | 0.59 (0.16–2.14) |
| ABCC5 rs2139560 G>A (A = 0.3027) | AA vs GG/GA | 212 (81) | 1.52 (0.79–2.90) | 78 (82) | 1.23 (0.34–4.44) |
| ABCG2 rs2231142 G>T (T = 0.1194) | GT/TT vs GG | 204 (78) | 1.54 (0.83–2.87)* | 78 (82) | 7.15 (0.87–58.73)* |
| ABCG2 rs13120400 T>C (C = 0.1052) | TT vs TC/CC | 110 (42) | 1.08 (0.65–1.79) | 37 (39) | 1.56 (0.61–4.02) |
| ADA rs73598374 C>T (T = 0.0513) | CC vs CT/TT | 33 (13) | 1.68 (0.80–3.54)* | 13 (14) | 1.22 (0.36–4.18) |
| ADORA2A rs5751876 C>T (C = 0.4423) | TT vs CC/CT | 213 (81) | 1.17 (0.62–2.22) | 81 (85) | 0.18 (0.04–0.76)* |
| AMPD1 rs17602729 G>A (A = 0.0381) | GG vs GA/AA | 45 (17) | 1.49 (0.78–2.86) | 17 (18) | 0.46 (0.12–1.80) |
| ATIC rs2372536 C>G (G = 0.2778) | GG vs CC/CG | 226 (86) | 1.69 (0.79–3.61)* | 86 (91) | 4.14 (0.48–35.53)* |
| FOLR2 rs514933 T>C (C = 0.4285) | TT/TC vs CC | 42 (16) | 1.24 (0.63–2.43) | 16 (17) | 1.06 (0.32–3.55) |
| FPGS rs4451422 A>C (C = 0.4643) | AA/AC vs CC | 61 (23) | 1.46 (0.80–2.66) | 19 (20) | 1.73 (0.59–5.07) |
| GGH rs3758149 G>A (A = 0.2316) | GG vs GA/AA | 137 (52) | 1.58 (0.95–2.61)* | 41 (43) | 0.90 (0.35–2.30) |
| GGH rs10106587 A>C (C = 0.2576) | AC/CC vs AA | 134 (51) | 1.02 (0.62–1.69) | 43 (45) | 0.77 (0.30–1.99) |
| ITPA rs1127354 G>T (A = 0.0895) | GT/TT vs GG | 229 (87) | 1.04 (0.50–2.16) | 79 (83) | 1.07 (0.29–3.94) |
| MTHFR rs1801131 A>C (G = 0.2494) | AA vs AC/CC | 139 (53) | 1.37 (0.83–2.27) | 42 (44) | 0.97 (0.38–2.49) |
| MTHFR rs1801133 C>T (A = 0.2454) | CT/TT vs CC | 125 (48) | 1.61 (0.97–2.66)* | 55 (58) | 0.68 (0.26–1.77) |
| MTRR rs1801394 A>G (G = 0.3642) | GG vs AA/AG | 174 (66) | 1.45 (0.85–2.47)* | 67 (71) | 0.52 (0.19–1.44) |
| SLC19A1 rs1051266 C>T (C = 0.4886) | TT vs CC/CT | 220 (84) | 1.48 (0.73–2.98) | 77 (81) | 2.20 (0.56–8.69) |
| SLC46A1 rs2239907 C>T (T = 0.4515) | CC/CT vs TT | 52 (20) | 1.94 (1.04–3.60)* | 13 (14) | 1.30 (0.33–5.09) |
| Metabolic parameters | |||||
| Erythrocyte-folate<750 nmol/L | 74 (37) | 1.48 (0.82–2.69)* | 14 (14) | 2.80 (0.80–9.79)* | |
| Serum-folate<13 nmol/L | 57 (24) | 1.43 (0.77–2.66) | 25 (25) | 0.95 (0.33–2.74) | |
| Plasma homocysteine>14 μmol/L | 64 (27) | 1.16 (0.64–2.11) | 34 (34) | 1.10 (0.43–2.81) | |
| Serum vitamin B6<80 nmol/L | 103 (50) | 1.40 (0.80–2.47) | 57 (58) | 1.23 (0.50–3.03) | |
| Serum vitamin B12>400 pmol/L | 61 (26) | 1.11 (0.61–2.03) | 20 (20) | 2.30 (0.78–6.82)* | |
| eGFR<80 ml/min/1.73m2 | 63 (53) | 1.43 (0.67–3.03) | 39 (38) | 1.35 (0.55–3.32) | |
| Disease activity | |||||
| ESR>40 mm/hour | 73 (26) | 2.77 (1.58–4.85)* | 18 (18) | 1.83 (0.61–5.50) | |
| CRP>10 mg/L | 125 (44) | 1.37 (0.74–2.54) | 31 (30) | 0.81 (0.31–2.13) | |
| TJC>3 joints | 221 (80) | 3.81 (1.95–7.43)* | 58 (57) | 3.78 (1.44–9.97) | |
| SJC>3 joints | 229 (80) | 2.05 (1.08–3.89)* | 55 (54) | 1.50 (0.62–3.64) | |
| VAS>34 mm | 215 (75) | 3.82 (2.00–7.32)* | 77 (76) | 1.44 (0.49–4.58) | |
| DAS28>5.1 | 125 (44) | 3.70 (2.23–6.16)* | 25 (25) | 5.96 (1.98–17.93)* | |
| HAQ>0.6 | 217 (76) | 2.80 (1.51–5.18)* | 88 (86) | 1.27 (0.35–4.63) | |
| Rheumatoid factor negative | 85 (34) | 1.58 (0.92–2.72)* | 55 (59) | 0.96 (0.38–2.47) | |
| Anti-CCP negative | 75 (30) | 1.41 (0.81–2.46) | 55 (59) | 1.68 (0.65–4.37) | |
| Disease duration>145 days | 143 (51) | 1.10 (0.68–1.78) | ** | ** | |
| Life style | |||||
| Smoking | 87 (33) | 2.01 (1.19–3.41)* | ** | ** | |
| Alcohol consumption<30 glasses/month | 191 (73) | 1.47 (0.84–2.58)* | 34 (76) | 2.25 (0.39–13.17) | |
| Cola consumption>30 glasses/month | 33 (13) | 1.28 (0.62–1.67) | 16 (16) | 1.64 (0.53–5.08) | |
| Coffee consumption<90 glasses/month | 117 (45) | 1.11 (0.68–1.83) | 50 (51) | 1.19 (0.48–2.93) | |
| Tea consumption>90 glasses/month | 57 (22) | 1.58 (0.87–2.88)* | 20 (20) | 0.19 (0.04–0.90)* | |
| BMI>25 kg/m2 | 157 (56) | 1.70 (1.04–2.79)* | ** | ** | |
*Variables significantly associated with MTX non-response (p<0.200) in the derivation cohort were included in the multivariate backward logistic regression analysis;
**not determined;
HCQ, hydroxychloroquine; TDT, triple disease-modifying antirheumatic drug therapy; GC, glucocorticoids; IM, intramuscular; NSAID, non-steroidal anti-inflammatory drugs; ABCB1, Adenosine triphosphate-binding cassette transporter B1; ADA, adenosine-deaminase; ADORA2A, adenosine A2A receptor; AMPD1, adenosine monophosphate deaminase 1; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase; FOLR2, Folate receptor 2; FPGS, folylpolyglutamate synthetase; GGH, γ-glutamyl hydrolase; ITPA, inosine triphosphatase; MTHFR, methylenetetrahydrofolate reductase; MTRR, methionine synthase reductase; SLC19A1, solute carrier 19A1; eGFR, estimated glomerular filtration rate; TJC, tender joint score in 28 joints; SJC, swollen joint score in 28 joints; HAQ, health assement questionnaire; CCP, cyclic citrulinated peptide; BMI, body mass index; MAF, Global minor allele frequency in NCBI SNP database.