Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

Table 2

Relation between clinicopathological variables and clinical response to methotrexate.

Characteristic	Response; (𝑛=105)	Nonresponse; (𝑛=128)	𝑃 value
Patient-related
Male, 𝑛 (%)	19 (51.4)	18 (48.6)	Reference
Female, 𝑛 (%)	86 (43.9)	110 (56.1)	0.402
Premenopausal, 𝑛 (%)	39 (39.0)	61 (61.0)	Reference
Postmenopausal, 𝑛 (%)	47 (49.0)	49 (51.0)	0.160
Age, mean ± SD, years	55.1±11.6	49.3±11.5	<0.001
BMI, median (IQR), Kg/m^2	26.2 (18.5–43.1)	26.3 (18.4–38.9)	0.574
Noncurrent smoker*, 𝑛 (%)	83 (41.3)	118 (58.7)	Reference
Current smoker, 𝑛 (%)	22 (68.8)	10 (31.2)	𝟎.𝟎𝟎𝟒^a
NPY**, median (IQR)	20.1 (1.5–120.0)	14.0 (0.8–40.0)	0.269
Noncomorbidity, 𝑛 (%)	51 (47.7)	56 (52.3)	Reference
Comorbidity***, 𝑛 (%)	54 (42.9)	72 (57.1)	0.462
Disease-related
Diagnosis age, mean ± SD, years	42.1±13.3	39.1±12.8	0.081
Disease duration, median (IQR), years	8.0 (1.0–53.0)	8.0 (0.5–38.0)	0.164
RF negative, 𝑛 (%)	42 (41.2)	60 (58.8)	Reference
RF positive, 𝑛 (%)	63 (48.1)	68 (51.9)	0.293
Anti-CCP negative, 𝑛 (%)	35 (60.3)	23 (39.7)	Reference
Anti-CCP positive, 𝑛 (%)	70 (40.0)	105 (60.0)	𝟎.𝟎𝟎𝟕^b
ANAs negative, 𝑛 (%)	83 (49.7)	84 (50.3)	Reference
ANAs positive, 𝑛 (%)	22 (33.3)	44 (66.7)	𝟎.𝟎𝟐𝟒^c
DAS28, mean ± SD	4.0±1.5	4.3±1.2	0.089
Individual variables—DAS28
TJC (out of 28), median (IQR)	3.0 (0.0–27.0)	5.0 (0.0–20.0)	0.007
SJC (out of 28), median (IQR)	2.0 (0.0–24.0)	4.0 (0.0–23.0)	0.008
ESR, median (IQR), minutes (1st hour)	19.0 (1.0–88.0)	17.0 (1.0–92.0)	0.509
Global health on VAS, median (IQR)	47.0 (0.0–100.0)	49.0 (0.0–100.0)	0.516
HAQ score, median (IQR)	1.1 (0.0–2.9)	1.5 (0.0–2.6)	0.006
Treatment-related §
Symptomatic
Noncorticosteroids, 𝑛 (%)	21 (46.7)	24 (53.3)	Reference
Corticosteroids, 𝑛 (%)	84 (44.7)	104 (55.3)	0.810
Non-NSAIDs, 𝑛 (%)	41 (65.1)	22 (34.9)	Reference
NSAIDs, 𝑛 (%)	64 (37.6)	106 (62.4)	<𝟎.𝟎𝟎𝟏^d
Supplements
Folic acid nonregular users, 𝑛 (%)	52 (45.2)	63 (54.8)	Reference
Folic acid regular users, 𝑛 (%)	53 (44.9)	65 (55.1)	0.963
Methotrexate administration characteristics
Dose, median (IQR), mg/week	15.0 (2.5–25.0)	20.0 (7.5–25.0)	<0.001
Treatment duration, median (IQR), months	28.0 (6.0–230.0)	29.0 (6.0–209.0)	0.204
Per os administration route, 𝑛 (%)	83 (41.3)	118 (58.7)	Reference
Subcutaneous administration route, 𝑛 (%)	22 (68.8)	10 (31.2)	𝟎.𝟎𝟎𝟒^e

∗Noncurrent smokers include the never smokers and the ex-smokers.
**NPY = (number of cigarettes smoked per day × number of years smoking)/20.
***Comorbidity was defined as the presence of diabetes mellitus, hypertension, dyslipidemia, and/or cardiac disorders beyond rheumatoid arthritis.
§Drugs coadministered with methotrexate when clinical response to methotrexate was recorded.
𝑃 value < 0.05 is considered to be of statistical significance (highlighted in bold).
^aOR = 0.32, 95% CI: 0.14–0.71. ^bOR = 2.28, 95% CI: 1.24–4.19. ^cOR = 1.98, 95% CI: 1.09–3.58. ^dOR = 3.09, 95% CI: 1.69–5.65. ^eOR = 0.32, 95% CI: 0.14–0.71.
ANAs: antinuclear antibodies; anti-CCP: anti-cyclic citrullinated peptide; BMI: body mass index; DAS28: disease activity score 28; ESR: erythrocyte sedimentation rate; HAQ: health assessment questionnaire; IQR: interquartile range; NPY: number of pack years; NSAIDs: nonsteroidal anti-inflammatory drugs; RF: rheumatoid factor; SD: standard deviation; SJC: swollen joints count; TJC: tender joints count; VAS: visual analog scale.