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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%).
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Pediatric Rheumatology

ISSN: 1546-0096