Skip to main content

Advertisement

Table 1 Prevalence, univariable ORs (95%-CI) and p-values for potential predictors of MTX intolerance at MTX start

From: Prediction of Methotrexate Intolerance in Juvenile Idiopathic Arthritis: a prospective, observational cohort study

  Cohort, n = 152
Variables Frequency n (%) a OR (95%-CI) p-value
Demographics  
  Female 92 (60.5) 1.34 (0.64-2.82) 0.432
  Age at disease onset >8 years 80 (52.6) 0.68 (0.34-1.36) 0.271
  Age at MTX start* >12 years 72 (47.4) 0.54 (0.27-1.07) 0.073
  Disease duration at MTX start >0.5 years 103 (67.8) 0.79 (0.37-1.70) 0.535
JIA category *b  
  Oligoarticular (persistent/extended) 62 (40.8) Reference 0.094
  Polyarticular (RF negative/positive) 64 (42.1) 1.91 (0.86-4.24)
  Other (systemic/psoriatic/enthesitis) 26 (17.1) 0.78 (0.27-2.31)
Disease characteristics  
  ANA*b,c Positive 84 (55.3) 1.98 (0.97-4.07) 0.057
  RFc Positive 16 (10.5) 1.52 (0.62-3.72) 0.352
  HLA-B27c Positive 11 (7.2) 0.78 (0.29-2.12) 0.510
  Uveitis Present 21 (13.8) 1.44 (0.55-3.78) 0.455
Disease activity  
  CHAQ disability scorec ≤0.250 36 (23.7) Reference 0.395
  0.250-1.875 88 (57.9) 0.61 (0.24-1.55)
  >1.875 15 (9.9) 0.72 (0.18-2.80)
  Parent/patient assessment of pain*b,c ≤3 cm 58 (38.2) Reference 0.086
3-6 cm 36 (23.7) 2.19 (0.84-5.67)
>6 cm 42 (27.6) 0.78 (0.30-2.02)
  Parent/patient global assessmentc >2.5 cm 90 (59.2) 0.79 (0.36-1.72) 0.494
  Active joints* >2 92 (60.5) 2.00 (0.91-4.41) 0.070
  Limited joints* >1 108 (71.1) 2.02 (0.92-4.46) 0.072
  PGAd ≤2 cm 50 (32.9) Reference 0.496
  2-5 cm 86 (56.6) 1.35 (0.53-3.47)
  >5 cm 16 (10.5) 0.87 (0.21-3.60)
  ESRc >15 mm/hr 74 (48.7) 1.46 (0.66-3.25) 0.341
  CRPc >10 mg/L 49 (32.2) 0.83 (0.40-1.74) 0.544
  JADAS-27*b,c ≤5 16 (10.5) Reference 0.048
  5-15 59 (38.8) 0.40 (0.11-1.40)
  >15 52 (34.2) 0.93 (0.25-3.44)
Biochemical variables c  
  Haemoglobin >7.5 mmol/L 78 (51.3) 1.18 (0.60-2.32) 0.620
  Leucocytes >7 × 109/L 96 (63.2) 1.21 (0.59-2.47) 0.606
  Thrombocytes*b >350 × 109/L 74 (48.7) 1.61 (0.82-3.16) 0.161
  AST >17 IU/L 96 (63.2) 1.08 (0.50-2.36) 0.635
  ALT*b >12 IU/L 101 (66.4) 0.41 (0.19-0.88) 0.019
  Creatinine*b >50 μmol/L 56 (36.8) 0.51 (0.24-1.08) 0.069
Medication  
  MTX dose, median (IQR) mg/m2/week 9.9 (9.0-11.2) NA
  MTX route oral 148 (97.4) NA
  MTX restarted   31 (20.4) 1.22 (0.48-3.11) 0.554
  Folic acid   150 (98.7) NA
  Anti-emetics   5 (3.3) NA
  NSAID   120 (78.9) 0.93 (0.38-2.28) 0.655
Single nucleotide polymorphisms c  
   MTHFR rs1801133 C > T TT 15 (9.9) 0.60 (0.21-1.69) 0.322
   MTHFR rs1801131 A > C CC/AC 79 (52.0) 1.65 (0.76-3.62) 0.201
   MTRR rs1801394 A > G* GG/AG 117 (77.0) 0.53 (0.24-1.20) 0.123
   RFC/SLC19A1 rs1051266 C > T* TT 17 (11.2) 1.77 (0.74-4.25) 0.194
   ITPA rs1127354 C > A AA/CA 15 (9.9) 0.62 (0.22-1.74) 0.350
   AMPD1 rs17602729 G > A AA/GA 41 (27.0) 1.46 (0.70-3.05) 0.304
   ATIC rs2372536 C > G GG/CG 93 (61.2) 0.84 (0.39-1.83) 0.614
   ADA22 rs73598374 C > T TT/CT 13 (8.6) NA
   ADORA2A rs5751876 C > T TT 28 (18.4) 1.54 (0.65-3.64) 0.319
   MDR-1/ABCB1 rs  128503 G > A* AA 32 (21.1) 1.73 (0.75-3.98) 0.190
   MDR-1/ABCB1 rs1045642 G > A AA 44 (28.9) 1.40 (0.65-3.01) 0.376
   MDR-1/ABCB1 rs2032582 C > A/T AA/TT 24 (15.8) 1.51 (0.63-3.64) 0.344
   MRP-1/ABCC1 rs35592 T > C CC/TC 52 (34.2) 0.79 (0.39-1.57) 0.494
   MRP-1/ABCC1 rs3784862 A > G GG/AG 73 (48.0) 0.97 (0.50-1.91) 0.824
   MRP-2/ABCC2 rs4148396 C > T TT 18 (11.8) 1.57 (0.60-4.08) 0.349
   MRP-2/ABCC2 rs717620 C > T TT/CT 44 (28.9) 0.82 (0.37-1.82) 0.626
   MRP-3/ABCC3 rs4793665 T > C CC/TC 92 (60.5) 0.73 (0.36-1.49) 0.381
   MRP-3/ABCC3 rs3785911 A > C* CC/AC 78 (51.3) 1.67 (0.84-3.32) 0.136
   MRP-4/ABCC4 rs868853 T > C CC/TC 22 (14.5) 0.88 (0.35-2.18) 0.734
   MRP-4/ABCC4 rs2274407 C > A AA/CA 20 (13.2) 1.33 (0.48-3.73) 0.514
   MRP-5/ABCC5 rs2139560 G > A AA/GA 92 (60.5) 1.31 (0.64-2.68) 0.450
   BCRP/ABCG2 rs13120400 T > C CC/TC 63 (41.4) 0.77 (0.38-1.59) 0.470
   BCRP/ABCG2 rs2231142 G > T TT/GT 30 (19.7) 0.96 (0.42-2.20) 0.744
   FPGS rs4451422 A > C CC/AC 102 (67.1) 1.37 (0.63-2.94) 0.417
   GGH rs10106587 A > C CC/AC 73 (48.0) 1.20 (0.59-2.46) 0.508
   GGH rs3758149 G > A AA/GA 77 (50.7) 1.20 (0.57-2.55) 0.602
   PCFT/SLC46A1 rs2239907 C > T TT/CT 104 (68.4) 1.49 (0.69-3.23) 0.306
  1. Abbreviations: ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, asparagine aminotransferase; CHAQ, childhood health assessment questionnaire; CI, confidence interval; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HLA, human leucocyte antigen; IQR, interquartile range; IU, international units; JADAS, juvenile arthritis disease activity score; JIA, juvenile idiopathic arthritis; MICE, multivariate imputation by chained equations; MTX, methotrexate; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; PGA, physician global assessment; RF, rheumatoid factor.
  2. *Variables associated with the outcome at p < 0.20 in the univariable logistic regression analysis. Variables with observed frequencies of <5 in the cross-tabulation with the outcome were excluded from the univariable logistic analysis: MTX route, use of folic acid, use of anti-emetics and ADA22 rs73598374.
  3. aFrequencies are based on observed data, not imputed data.
  4. bJIA category, ANA, parent/patient assessment of pain, JADAS-27, thrombocytes, ALT and creatinine were included in the multivariable logistic regression analysis.
  5. cMICE was used to impute missing values in the following variables (percentage of missing values): HLA-B27 (60.5), RF (19.1), JADAS-27 (16.4), CRP (15.8), parent/patient global assessment (11.8), RFC/SLC19A1 rs1051266 (11.8), creatinine (11.2), parent/patient assessment of pain (10.5), CHAQ disability score (8.6), MDR-1/ABCB1 rs2032582 (8.6), ALT (7.9), AST (7.2), ESR (5.3), GGH rs3758149 (4.6), MRP-2/ABCC2 rs717620 (3.9), MRP-4/ABCC4 rs868853 (3.9), MRP-5/ABCC5 rs2139560 (3.9), GGH rs10106587 (3.9), MTHFR rs1801131 (3.3), ATIC rs2372536 (3.3), ADORA2A rs5751876 (3.3), MRP-1/ABCC1 rs3784862 (3.3), MRP-2/ABCC2 rs4148396 (3.3), MRP-3/ABCC3 rs4793665 (3.3), BCRP/ABCG2 rs13120400 (3.3), PCFT/SLC46A1 rs2239907 (3.3), MTHFR rs1801133 (2.6), MTRR rs1801394 (2.6), ITPA rs1127354 (2.6), AMPD1 rs17602729 (2.6), ADA22 rs73598374 (2.6), MDR-1/ABCB1 rs1128503 and rs1045642 (2.6), MRP-1/ABCC1 rs35592 (2.6), MRP-3/ABCC3 rs3785911 (2.6), MRP-4/ABCC4 rs2274407 (2.6), BCRP/ABCG2 rs2231142 (2.6), FPGS rs4451422 (2.6), thrombocytes (2.0), ANA (2.0), hemoglobin (1.3), leucocytes (1.3).
  6. dPGA was determined retrospectively by an experienced physician (SJV) in 20 visits (13.2%).