Background
Methods
Data retrieval
Study outcomes
Statistical analyses
Results
TNFα-inhibitor cohort | Non-biologic cohort | ||
---|---|---|---|
Non-imputed | Non-imputed | ||
N= | 11995 | 3632 | |
Age | Years | 56 (12) | 60 (12) |
Gender | Female | 76 % | 73 % |
Ethnicity | White | 96 % | 98 % |
BMI | Kg.m−2 | 27.0 (7.1) | 27.4 (6.6) |
Smoking | Current | 22 % | 24 % |
Ex- | 38 % | 40 % | |
Never | 40 % | 37 % | |
DAS28 | 6.6 (1.0) | 5.1 (1.3) | |
TJC | 16 (7) | 8 (7) | |
SJC | 11 (6) | 6 (5) | |
ESR | 46 (29) | 35 (25) | |
VAS-GH | 73 (20) | 55 (24) | |
DAS28-P | 0.48 (0.07) | 0.44 (0.10) | |
Duration of RA | Years | 13 (10) | 10 (10) |
Serology | Positive | 65 % | 58 % |
Erosions | Yes | 63 % | 46 % |
Extra-articular | Yes | 29 % | 19 % |
Comorbidity | Yes | 60 % | 65 % |
HAQ | 2.0 (0.6) | 1.5 (0.8) | |
SF36-Vitality | 33 (10) | 39 (10) | |
SF36-Mental Health | 40 (11) | 45 (11) | |
SF36-Physical function | 16 (11) | 24 (14) | |
SF36-Bodily Pain | 25 (7) | 31 (9) | |
Steroids at baseline | 44 % | 23 % | |
DMARD at baseline | Methotrexate | 58 % | 65 % |
Sulphasalazine | 15 % | 32 % | |
Azathioprine | 2 % | 2 % | |
Leflunomide | 8 % | 12 % | |
D-penicillamine | 1 % | 1 % | |
Gold | 2 % | 5 % | |
Hydroxychloroquine | 10 % | 15 % | |
Ciclosporin | 1 % | 2 % | |
Cyclophosphamide | 0.10 % | 0.10 % |
Tertile or group | TNFα-inhibitor cohort | Non-biologic cohort | |||||||
---|---|---|---|---|---|---|---|---|---|
Original | Imputed (20 sets) | p | Original | p | Imputed (20 sets) | p | |||
Age | Youngest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 1.06 (0.97 - 1.17) | 0.230 | 1.06 (0.97 - 1.16) | 0.203 | 1.09 (0.91 - 1.30) | 0.366 | 1.04 (0.89 - 1.22) | 0.657 | |
Oldest | 0.98 (0.89 - 1.07) | 0.621 | 0.99 (0.90 - 1.08) | 0.815 | 1.05 (0.88 - 1.26) | 0.617 | 0.97 (0.83 - 1.14) | 0.746 | |
Gender | Male (ref) | 1 | 1 | 1 | 1 | ||||
Female |
1.11 (1.01 - 1.21)
|
0.033
|
1.10 (1.01 - 1.20)
|
0.033
| 1.06 (0.90 - 1.25) | 0.504 | 1.04 (0.90 - 1.20) | 0.656 | |
BMI | <25 (ref) | 1 | 1 | 1 | 1 | ||||
25 to <30 | 1.00 (0.91 - 1.10) | 0.961 | 1.01 (0.92 - 1.10) | 0.877 | 1.06 (0.89 - 1.26) | 0.534 | 1.02 (0.88 - 1.19) | 0.816 | |
≥30 |
1.23 (1.11 - 1.37)
|
<0.001
|
1.22 (1.11 - 1.34)
|
<0.001
|
1.56 (1.29 - 1.89)
|
<0.001
|
1.44 (1.22 - 1.70)
|
<0.001
| |
Smoking | Never (ref) | 1 | 1 | 1 |
1
| ||||
Ex | 1.09 (1.00 - 1.19) | 0.052 |
1.09 (1.00 - 1.18)
|
0.042
|
1.34 (1.14 - 1.58)
|
0.001
|
1.26 (1.08 - 1.46)
|
0.003
| |
Current |
1.20 (1.08 - 1.33)
|
<0.001
|
1.19 (1.08 - 1.31)
|
0.001
|
1.58 (1.30 - 1.93)
|
<0.001
|
1.54 (1.30 - 1.83)
|
<0.001
| |
DAS28 | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.49 (1.34 - 1.65)
|
<0.001
|
1.49 (1.35 - 1.65)
|
<0.001
|
2.00 (1.65 - 2.42)
|
<0.001
|
2.03 (1.72 - 2.39)
|
<0.001
| |
Highest |
2.94 (2.65 - 3.25)
|
<0.001
|
2.91 (2.64 - 3.21)
|
<0.001
|
4.26 (3.48 - 5.20)
|
<0.001
|
3.99 (3.37 - 4.72)
|
<0.001
| |
DAS28-P | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.50 (1.36 - 1.66)
|
<0.001
|
1.48 (1.35 - 1.63)
|
<0.001
|
2.03 (1.67 - 2.48)
|
<0.001
|
1.97 (1.67 - 2.33)
|
<0.001
| |
Highest |
1.63 (1.47 - 1.80)
|
<0.001
|
1.62 (1.47 - 1.78)
|
<0.001
|
2.45 (2.00 - 2.99)
|
<0.001
|
2.58 (2.17 - 3.05)
|
<0.001
| |
ESR | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.35 (1.22 - 1.50)
|
<0.001
|
1.34 (1.22 - 1.47)
|
<0.001
|
1.27 (1.05 - 1.53)
|
0.012
|
1.21 (1.03 - 1.42)
|
0.020
| |
Highest |
1.85 (1.68 - 2.05)
|
<0.001
|
1.81 (1.65 - 1.99)
|
<0.001
|
1.84 (1.52 - 2.22)
|
<0.001
|
1.69 (1.44 - 1.98)
|
<0.001
| |
SJC | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 1.09 (0.98 - 1.20) | 0.100 | 1.08 (0.98 - 1.18) | 0.106 |
1.24 (1.03 - 1.48)
|
0.023
|
1.19 (1.01 - 1.40)
|
0.037
| |
Highest |
1.27 (1.16 - 1.40)
|
<0.001
|
1.28 (1.17 - 1.40)
|
<0.001
|
1.50 (1.26 - 1.79)
|
<0.001
|
1.51 (1.29 - 1.76)
|
<0.001
| |
VAS-GH | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.81 (1.63 - 2.01)
|
<0.001
|
1.83 (1.66 - 2.02)
|
<0.001
|
2.64 (2.19 - 3.18)
|
<0.001
|
2.66 (2.25 - 3.15)
|
<0.001
| |
Highest |
5.21 (4.69 - 5.78)
|
<0.001
|
4.89 (4.44 - 5.40)
|
<0.001
|
5.45 (4.48 - 6.63)
|
<0.001
|
5.28 (4.44 - 6.28)
|
<0.001
| |
TJC | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.35 (1.22 - 1.49)
|
<0.001
|
1.34 (1.22 - 1.47)
|
<0.001
|
1.55 (1.29 - 1.85)
|
<0.001
|
1.63 (1.39 - 1.91)
|
<0.001
| |
Highest |
1.91 (1.73 - 2.11)
|
<0.001
|
1.91 (1.74 - 2.10)
|
<0.001
|
3.13 (2.58 - 3.78)
|
<0.001
|
3.01 (2.61 - 3.65)
|
<0.001
| |
Duration | Shortest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 0.98 (0.89 - 1.08) | 0.696 | 0.99 (0.90 - 1.08) | 0.799 |
1.25 (1.05 - 1.50)
|
0.015
| 1.15 (0.98 - 1.35) | 0.088 | |
Longest | 1.03 (0.93 - 1.13) | 0.612 | 1.03 (0.95 - 1.13) | 0.479 |
1.34 (1.12 - 1.60)
|
0.002
|
1.25 (1.07 - 1.47)
|
0.006
| |
Serology | Seronegative (ref) | 1 | 1 | 1 | 1 | ||||
Seropositive | 1.08 (0.99 - 1.17) | 0.072 | 1.07 (0.99 - 1.16) | 0.071 | 1.09 (0.94 - 1.26) | 0.246 | 1.04 (0.91 - 1.19) | 0.545 | |
Erosions | None (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 0.97 (0.91 - 1.06) | 0.426 | 0.97 (0.90 - 1.05) | 0.450 | 1.01 (0.88 - 1.17) | 0.882 | 0.99 (0.87 - 1.13) | 0.947 | |
Extra-articular manifestation | No (ref) | 1 | 1 | 1 | 1 | ||||
Yes |
1.16 (1.09 - 1.27)
|
<0.001
|
1.16 (1.07 - 1.26)
|
<0.001
| 1.16 (0.96 - 1.39) | 0.120 | 1.18 (1.00 - 1.40) | 0.053 | |
Co-morbidity | No (ref) | 1 | 1 | 1 | 1 | ||||
Yes |
1.30 (1.19 - 1.38)
|
<0.001
|
1.28 (1.19 - 1.38)
|
<0.001
|
1.56 (1.34 - 1.81)
|
<0.001
|
1.52 (1.32 - 1.74)
|
<0.001
| |
HAQ | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 0.98 (0.89 - 1.08) | 0.682 | 0.99 (0.91 - 1.09) | 0.870 |
5.04 (4.09 - 6.22)
|
<0.001
|
4.55 (3.80 - 5.44)
|
<0.001
| |
Highest | 1.10 (0.99 - 1.21) | 0.068 | 1.05 (0.96 - 1.15) | 0.329 |
19.44 (15.38 - 24.56)
|
<0.001
|
16.30 (13.31 - 19.95)
|
<0.001
| |
SF36-Vitality | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.83 (1.64 - 2.05)
|
<0.001
|
1.86 (1.68 - 2.06)
|
<0.001
|
3.19 (2.61 - 3.90)
|
<0.001
|
2.99 (2.51 - 3.56)
|
<0.001
| |
Worst |
5.61 (5.05 - 6.22)
|
<0.001
|
5.31 (4.82 - 5.86)
|
<0.001
|
8.89 (7.25 - 10.89)
|
<0.001
|
8.35 (6.97 - 10.00)
|
<0.001
| |
SF36-Mental Health | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.92 (1.73 - 2.14)
|
<0.001
|
1.96 (1.78 - 2.17)
|
<0.001
|
2.87 (2.37 - 3.48)
|
<0.001
|
2.65 (2.24 - 3.12)
|
<0.001
| |
Worst |
4.39 (3.98 - 4.85)
|
<0.001
|
4.35 (3.96 - 4.78)
|
<0.001
|
7.03 (5.71 - 8.67)
|
<0.001
|
5.65 (4.75 - 6.71)
|
<0.001
| |
SF36-Physical Function | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
2.70 (2.41 - 3.01)
|
<0.001
|
2.55 (2.29 - 2.81)
|
<0.001
|
3.35 (2.75 - 4.09)
|
<0.001
|
3.05 (2.56 - 3.64)
|
<0.001
| |
Worst |
9.29 (8.32 - 10.38)
|
<0.001
|
8.17 (7.38 - 9.05)
|
<0.001
|
16.53 (13.13 - 20.81)
|
<0.001
|
12.84 (10.60 - 15.56)
|
<0.001
| |
Steroids | Not (ref) | 1 | 1 | 1 |
1
| ||||
At baseline |
1.28 (1.17 - 1.39)
|
<0.001
|
1.25 (1.16 - 1.35)
|
<0.001
|
1.44 (1.21 - 1.71)
|
<0.001
|
1.44 (1.23 - 1.68)
|
<0.001
| |
Methotrexate | Not (ref) | 1 |
1
| 1 |
1
| ||||
At baseline |
0.77 (0.71 - 0.84)
|
<0.001
|
0.75 (0.69 - 0.82)
|
<0.001
| 0.92 (0.79 - 1.07) | 0.276 | 0.92 (0.80 - 1.05) | 0.210 | |
Sulphasalazine | Not (ref) | 1 |
1
| 1 |
1
| ||||
At baseline |
0.86 (0.77 - 0.96)
|
0.007
|
0.86 (0.78 - 0.96)
|
0.006
| 0.88 (0.75 - 1.03) | 0.104 |
0.84 (0.73 - 0.96)
|
0.012
| |
Lefunomide | Not (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 1.01 (0.88 - 1.17) | 0.882 | 0.99 (0.86 - 1.14) | 0.942 |
1.50 (1.20 - 1.87)
|
<0.001
|
1.48 (1.21 - 1.80)
|
<0.001
| |
Azathioprine | Not (ref) | 1 | 1 | 1 |
1
| ||||
At baseline | 1.03 (0.79 - 1.35) | 0.836 | 1.04 (0.80 - 1.34) | 0.796 |
1.85 (1.12 - 3.08)
|
0.018
|
1.79 (1.12 - 2.86)
|
0.016
| |
Hydroxychloroquine | Not (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 0.89 (0.78 - 1.02) | 0.100 | 0.90 (0.79 - 1.02) | 0.094 | 0.89 (0.73 - 1.09) | 0.280 | 0.94 (0.78 - 1.13) | 0.519 | |
Gold | Not (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 1.06 (0.77 - 1.44) | 0.750 | 1.01 (0.75 - 1.37) | 0.941 |
1.77 (1.24 - 2.52)
|
0.002
|
1.62 (1.18 - 2.21)
|
0.002
|
Tertile or group | TNFα-inhibitor cohort | Non-biologic cohort | |||||||
---|---|---|---|---|---|---|---|---|---|
Complete case | Imputed | Complete case | Imputed | ||||||
Crude OR (95 % CI) | p | Crude OR (95 % CI) | p | Crude OR (95 % CI) | p | Crude OR (95 % CI) | p | ||
Age | Youngest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.35 (1.21 – 1.51)
|
<0.001
|
1.35 (1.21 – 1.51)
|
<0.001
|
1.39 (1.13 - 1.71)
|
0.002
|
1.39 (1.13 - 1.71)
|
0.002
| |
Oldest |
1.67 (1.50 – 1.87)
|
<0.001
|
1.67 (1.50 – 1.87)
|
<0.001
|
1.41 (1.15 - 1.74)
|
0.001
|
1.41 (1.15 - 1.74)
|
0.001
| |
Gender | Male (ref) | 1 | 1 | 1 | 1 | ||||
Female |
0.88 (0.79 – 0.98)
|
0.015
|
0.88 (0.79 – 0.98)
|
0.015
| 1.10 (0.91 - 1.33) | 0.358 | 1.10 (0.91 - 1.33) | 0.358 | |
BMI | <25 (ref) | 1 | 1 | 1 | 1 | ||||
25 to <30 |
1.24 (1.11 - 1.38)
|
<0.001
|
1.22 (1.10 - 1.35)
|
<0.001
| 1.12 (0.92 - 1.37) | 0.264 | 1.12 (0.92 - 1.35) | 0.276 | |
≥30 |
1.53 (1.36 - 1.73)
|
<0.001
|
1.48 (1.33 - 1.66)
|
<0.001
|
1.61 (1.29 - 2.00)
|
<0.001
|
1.60 (1.30 - 1.98)
|
<0.001
| |
Smoking | Never (ref) | 1 | 1 |
1
|
1
| ||||
Ex |
1.23 (1.11 - 1.36)
|
<0.001
|
1.23 (1.12 - 1.36)
|
<0.001
|
1.33 (1.12 - 1.59)
|
0.002
|
1.37 (1.14 - 1.65)
|
0.001
| |
Current |
1.39 (1.23 - 1.56)
|
<0.001
|
1.39 (1.23 - 1.56)
|
<0.001
| 1.24 (1.00 - 1.53) | 0.054 | 1.24 (1.00 - 1.53) | 0.054 | |
DAS28 | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.20 (1.07 – 1.34)
|
0.002
|
1.20 (1.07 – 1.34)
|
0.002
|
1.29 (1.04 - 1.59)
|
0.021
|
1.31 (1.07 - 1.61)
|
0.010
| |
Highest |
1.64 (1.47 – 1.84)
|
<0.001
|
1.64 (1.47 – 1.84)
|
<0.001
|
1.96 (1.58 - 2.43)
|
<0.001
|
1.95 (1.59 - 2.39)
|
<0.001
| |
DAS28-P | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.15 (1.03 – 1.29)
|
0.013
|
1.15 (1.03 – 1.29)
|
0.013
|
1.65 (1.32 - 2.07)
|
<0.001
|
1.59 (1.28 - 1.97)
|
<0.001
| |
Highest |
1.46 (1.30 – 1.63)
|
<0.001
|
1.46 (1.30 – 1.63)
|
<0.001
|
2.26 (1.80 - 2.85)
|
<0.001
|
2.20 (1.77 - 2.73)
|
<0.001
| |
ESR | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 1.00 (0.90 - 1.12) | 0.977 | 1.00 (0.90 - 1.12) | 0.978 | 1.12 (0.91 - 1.38) | 0.306 | 1.06 (0.87 - 1.30) | 0.571 | |
Highest |
1.14 (1.02 – 1.27)
|
0.019
|
1.14 (1.03 - 1.27)
|
0.016
|
1.24 (1.00 - 1.54)
|
0.049
|
1.21 (0.99 - 1.48)
|
0.070
| |
SJC | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 0.97 (0.87 – 1.08) | 0.576 | 0.97 (0.87 – 1.08) | 0.580 | 0.88 (0.71 - 1.09) | 0.268 | 0.89 (0.73 - 1.10) | 0.295 | |
Highest | 1.03 (0.93 - 1.14) | 0.608 | 1.03 (0.93 - 1.14) | 0.593 | 0.96 (0.78 - 1.15) | 0.613 | 0.94 (0.77 - 1.14) | 0.549 | |
VAS-GH | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.28 (1.15 – 1.43)
|
<0.001
|
1.27 (1.14 - 1.42)
|
<0.001
|
1.82 (1.48 - 2.24)
|
<0.001
|
1.81 (1.48 - 2.23)
|
<0.001
| |
Highest |
1.84 (1.65 - 2.06)
|
<0.001
|
1.84 (1.65 - 2.05)
|
<0.001
|
2.83 (2.29 - 3.49)
|
<0.001
|
2.82 (2.28 - 3.47)
|
<0.001
| |
TJC | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.12 (1.01 – 1.25)
|
0.040
|
1.12 (1.01 – 1.25)
|
0.037
|
1.54 (1.25 - 1.88)
|
<0.001
|
1.52 (1.25 - 1.86)
|
<0.001
| |
Highest |
1.42 (1.27 - 1.59)
|
<0.001
|
1.42 (1.28 - 1.59)
|
<0.001
|
2.11 (1.71 - 2.60)
|
<0.001
|
2.08 (1.69 - 2.56)
|
<0.001
| |
Duration | Shortest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 1.04 (0.93 – 1.16) | 0.484 | 1.04 (0.93 – 1.16) | 0.468 |
1.44 (1.17 - 1.77)
|
0.001
|
1.44 (1.17 - 1.77)
|
0.001
| |
Longest |
1.22 (1.09 – 1.35)
|
<0.001
|
1.21 (1.09 - 1.35)
|
<0.001
|
1.55 (1.27 - 1.91)
|
<0.001
|
1.55 (1.26 - 1.90)
|
<0.001
| |
Serology | Seronegative (ref) | 1 | 1 | 1 | 1 | ||||
Seropositive | 0.98 (0.89 - 1.07) | 0.657 | 0.98 (0.89 - 1.07) | 0.674 | 1.05 (0.89 - 1.24) | 0.578 | 1.05 (0.89 - 1.24) | 0.608 | |
Erosions | None (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 0.92 (0.84 – 1.01) | 0.091 | 0.93 (0.85 - 1.01) | 0.096 | 1.16 (0.98 - 1.37) | 0.082 | 1.16 (0.98 - 1.37) | 0.090 | |
Extra-articular manifestation | No (ref) | 1 | 1 | 1 | 1 | ||||
Yes |
1.20 (1.09 – 1.32)
|
<0.001
|
1.20 (1.09 – 1.32)
|
<0.001
| 1.21 (0.99 - 1.49) | 0.071 | 1.21 (0.99 - 1.49) | 0.071 | |
Co-morbidity | No (ref) |
1
|
1
| 1 | 1 | ||||
Yes |
1.66 (1.51 – 1.81)
|
<0.001
|
1.66 (1.51 – 1.81)
|
<0.001
|
1.82 (1.53 - 2.18)
|
<0.001
|
1.82 (1.53 - 2.18)
|
<0.001
| |
HAQ | Lowest (ref) | 1 | 1 | 1 | 1 | ||||
Mid | 0.98 (0.87 - 1.09) | 0.667 | 0.98 (0.88 - 1.09) | 0.680 |
3.03 (2.40 - 3.83)
|
<0.001
|
2.84 (2.28 - 3.54)
|
<0.001
| |
Highest | 1.01 (0.90 - 1.13) | 0.909 | 1.02 (0.91 - 1.13) | 0.804 |
10.63 (8.25 - 13.70)
|
<0.001
|
9.17 (7.23 - 11.62)
|
<0.001
| |
SF36-Vitality | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.23 (1.09 - 1.38)
|
0.001
|
1.21 (1.08 - 1.35)
|
0.001
|
2.40 (1.90 - 3.03)
|
<0.001
|
2.29 (1.84 - 2.85)
|
<0.001
| |
Worst |
1.90 (1.70 - 2.12)
|
<0.001
|
1.84 (1.66 - 2.05)
|
<0.001
|
5.40 (4.30 - 6.80)
|
<0.001
|
4.87 (3.92 - 6.06)
|
<0.001
| |
SF36-Mental Health | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
1.69 (1.51 - 1.90)
|
<0.001
|
1.66 (1.49 - 1.85)
|
<0.001
|
2.08 (1.66 - 2.59)
|
<0.001
|
2.26 (1.84 - 2.78)
|
<0.001
| |
Worst |
2.40 (2.15 - 2.68)
|
<0.001
|
2.29 (2.07 - 2.56)
|
<0.001
|
4.26 (3.36 - 5.41)
|
<0.001
|
3.90 (3.15 - 4.83)
|
<0.001
| |
SF36-Physical Function | Best (ref) | 1 | 1 | 1 | 1 | ||||
Mid |
2.01 (1.80 - 2.26)
|
<0.001
|
1.95 (1.74 - 2.17)
|
<0.001
|
3.29 (2.60 0 4.15)
|
<0.001
|
2.70 (2.16 - 3.38)
|
<0.001
| |
Worst |
3.83 (3.41 - 4.30)
|
<0.001
|
3.62 (3.23 - 4.04)
|
<0.001
|
9.55 (7.40 - 12.34)
|
<0.001
|
7.72 (6.15 - 9.72)
|
<0.001
| |
Steroids | Not (ref) |
1
|
1
|
1
|
1
| ||||
At baseline |
1.58 (1.44 - 1.74)
|
<0.001
|
1.58 (1.44 - 1.74)
|
<0.001
|
1.61 (1.32 - 1.96)
|
<0.001
|
1.61 (1.32 - 1.96)
|
<0.001
| |
Methotrexate | Not (ref) | 1 | 1 |
1
|
1
| ||||
At baseline |
0.63 (0.57 - 0.69)
|
<0.001
|
0.63 (0.57 - 0.69)
|
<0.001
|
0.79 (0.67 - 0.95)
|
0.010
|
0.79 (0.67 - 0.95)
|
0.010
| |
Sulphasalazine | Not (ref) |
1
|
1
| 1 | 1 | ||||
At baseline |
0.69 (0.61 - 0.78)
|
<0.001
|
0.69 (0.61 - 0.78)
|
<0.001
| 0.85 (0.71 - 1.02) | 0.076 | 0.85 (0.71 - 1.02) | 0.076 | |
Lefunomide | Not (ref) | 1 | 1 | 1 | 1 | ||||
At baseline |
1.26 (1.07 - 1.49)
|
0.006
|
1.26 (1.07 - 1.49)
|
0.006
|
1.66 (1.28 - 2.16)
|
<0.001
|
1.66 (1.28 - 2.16)
|
<0.001
| |
Azathioprine | Not (ref) | 1 | 1 |
1
|
1
| ||||
At baseline |
1.44 (1.07 - 1.95)
|
<0.001
|
1.44 (1.07 - 1.95)
|
<0.001
|
2.63 (1.37 - 5.03)
|
0.004
|
2.63 (1.37 - 5.03)
|
0.004
| |
Hydroxychloroquine | Not (ref) | 1 | 1 |
1
|
1
| ||||
At baseline |
0.67 (0.57 - 0.78)
|
<0.001
|
0.67 (0.57 - 0.78)
|
<0.001
| 0.81 (0.64 - 1.03) | 0.084 | 0.81 (0.64 - 1.03) | 0.084 | |
Gold | Not (ref) | 1 | 1 | 1 | 1 | ||||
At baseline | 1.24 (0.87 - 1.76) | 0.273 | 1.24 (0.87 - 1.76) | 0.273 |
1.50 (1.02 - 2.20)
|
0.047
|
1.50 (1.02 - 2.20)
|
0.047
|
Higher than median pain score - 1 year | |||||||||
---|---|---|---|---|---|---|---|---|---|
Variable at baseline | Tertile or group at baseline | TNFα-inhibitors cohort | Non-biologic cohort | ||||||
Complete case | Imputed | Complete case | Imputed | ||||||
aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | ||
Age | Tertiles |
1.14 (1.06 - 1.22)
|
0.001
|
1.19 (1.12 - 1.27)
|
<0.001
| 1.06 (0.90 - 1.25) | 0.470 | 1.03 (0.89 - 1.18) | 0.728 |
Gender | Female |
0.84 (0.73 - 0.96)
|
0.013
|
0.84 (0.74 - 0.94)
|
0.003
| 0.86 (0.65 - 1.14) | 0.296 | 0.90 (0.71 - 1.15) | 0.317 |
BMI | WHO groups |
1.12 (1.05 - 1.21)
|
0.002
|
1.13 (1.05 - 1.21)
|
0.001
| 1.06 (0.91 - 1.24) | 0.463 | 1.07 (0.93 - 1.22) | 0.353 |
Smoking | Current |
1.25 (1.07 - 1.46)
|
0.006
|
1.28 (1.11 - 1.47)
|
<0.001
| 0.98 (0.70 - 1.38) | 0.924 | 1.16 (0.87 - 1.54) | 0.317 |
Smoking | Ex- | 1.03 (0.90 - 1.17) | 0.678 | 1.05 (0.94 - 1.17) | 0.421 | 1.14 (0.87 - 1.49) | 0.344 | 1.16 (0.92 - 1.46) | 0.698 |
DAS28 | Tertiles | 1.02 (0.95 - 1.10) | 0.638 | 1.01 (0.95 - 1.08) | 0.640 |
0.80 (0.68 - 0.94)
|
0.007
|
0.86 (0.75 - 0.99)
|
0.041
|
DAS28-P | Tertiles |
1.13 (1.05 - 1.21)
|
0.001
|
1.14 (1.07 - 1.21)
|
<0.001
|
1.26 (1.08 - 1.47)
|
0.003
|
1.27 (1.11 - 1.46)
|
0.001
|
Duration | Tertiles | 1.04 (0.97 - 1.12) | 0.264 | 1.01 (0.95 - 1.08) | 0.660 | 1.08 (0.92 - 1.27) | 0.326 | 1.08 (0.94 - 1.24) | 0.265 |
Serology | Positive | 0.91 (0.81 - 1.03) | 0.127 | 0.96 (0.86 - 1.07) | 0.440 | 1.01 (0.79 - 1.30) | 0.919 | 1.04 (0.84 - 1.29) | 0.696 |
Erosions | Positive | 0.93 (0.82 - 1.05) | 0.244 | 0.94 (0.85 - 1.05) | 0.282 | 0.98 (0.75 - 1.27) | 0.848 | 1.02 (0.82 - 1.28) | 0.838 |
Extra-articular manifestation | Yes | 1.09 (0.96 - 1.23) | 0.191 | 1.06 (0.95 - 1.18) | 0.305 | 1.03 (0.77 - 1.39) | 0.840 | 0.95 (0.74 - 1.22) | 0.698 |
Co-morbidity | Yes |
1.27 (1.12 - 1.43)
|
<0.001
|
1.29 (1.16 - 1.43)
|
<0.001
|
1.31 (1.01 - 1.70)
|
0.041
| 1.24 (1.00 - 1.55) | 0.055 |
HAQ | Tertiles | 0.98 (0.91 - 1.05) | 0.553 | 0.99 (0.93 - 1.05) | 0.703 |
1.44 (1.17 - 1.78)
|
<0.001
|
1.55 (1.29 - 1.87)
|
<0.001
|
SF36-Vitality | Tertiles | 0.95 (0.88 1.03) | 0.183 | 0.97 (0.91 - 1.04) | 0.382 |
1.31 (1.10 - 1.55)
|
0.002
|
1.21 (1.04 - 1.40)
|
0.015
|
SF36-Mental Health | Tertiles |
1.25 (1.17 - 1.35)
|
<0.001
|
1.23 (1.15 - 1.31)
|
<0.001
|
1.29 (1.08 - 1.53)
|
0.005
|
1.29 (1.11 - 1.50)
|
0.001
|
SF36-Physical Function | Tertiles |
1.51 (1.40 - 1.63)
|
<0.001
|
1.47 (1.37 - 1.57)
|
<0.001
|
1.44 (1.18 - 1.76)
|
<0.001
|
1.36 (1.14 - 1.62)
|
<0.001
|
SF36-Bodily Pain | Tertiles |
1.49 (1.38 - 1.62)
|
<0.001
|
1.46 (1.36 - 1.57)
|
<0.001
|
1.99 (1.64 - 2.42)
|
<0.001
|
1.77 (1.49 - 2.10)
|
<0.001
|
Steroid | At baseline |
1.24 (1.09 - 1.40)
|
0.001
|
1.28 (1.15 - 1.43)
|
<0.001
| 1.25 (0.94 - 1.67) | 0.124 |
1.35 (1.06 - 1.73)
|
0.016
|
Methotrexate | At baseline |
0.80 (0.71 - 0.91)
|
0.001
|
0.81 (0.72 - 0.92)
|
<0.001
| 0.84 (0.61 - 1.14) | 0.250 | 0.91 (0.70 - 1.19) | 0.508 |
Sulphasalazine | At baseline |
0.80 (0.68 - 0.94)
|
0.008
|
0.81 (0.70 - 0.93)
|
0.003
| 0.87 (0.65 - 1.16) | 0.337 | 0.98 (0.76 - 1.25) | 0.845 |
Lefunomide | At baseline | 1.18 (0.97 - 1.44) | 0.107 |
1.20 (1.01 - 1.43)
|
0.038
| 1.13 (0.73 - 1.74) | 0.595 | 1.18 (0.81 - 1.71) | 0.394 |
Azathioprine | At baseline |
1.40 (1.02 - 1.93)
|
0.036
| 1.18 (0.89 - 1.56) | 0.245 | 1.26 (0.49 - 3.24) | 0.637 | 1.87 (0.83 - 4.19) | 0.131 |
Hydroxychloroquine | At baseline | 0.83 (0.68 - 1.01) | 0.061 |
0.83 (0.70 - 0.99)
|
0.034
| 0.82 (0.59 - 1.15) | 0.248 | 0.90 (0.68 - 1.20) | 0.473 |
Gold | At baseline | 0.93 (0.65 - 1.31) | 0.664 | 1.03 (0.75 - 1.40) | 0.858 | 1.20 (0.69 - 2.07) | 0.523 | 1.22 (0.75 - 1.99) | 0.428 |
Discontinuation of TNFα-inhibitors | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Variable at baseline | Tertile or group at baseline | All reasons | Lack of Efficacy | Adverse Drug Reaction | |||||||||
Complete case | Imputed | Complete case | Imputed | Complete case | Imputed | ||||||||
aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | aOR (95 % CI) | p | ||
Age | Tertiles | 1.03 (0.96 - 1.10) | 0.384 | 1.04 (0.98 - 1.11) | 0.155 | 0.99 (0.90 - 1.09) | 0.856 | 1.02 (0.94 - 1.11) | 0.643 | 1.07 (0.98 - 1.17) | 0.149 |
1.10 (1.02 - 1.19)
|
0.020
|
Gender | Female | 1.12 (0.99 - 1.27) | 0.062 |
1.16 (1.04 - 1.28)
|
0.007
| 1.18 (0.99 - 1.40) | 0.063 |
1.18 (1.02 - 1.37)
|
0.029
| 1.11 (0.94 - 1.32) | 0.212 |
1.14 (0.99 - 1.32)
|
0.077
|
BMI | WHO | 0.99 (0.93 - 1.05) | 0.673 | 0.98 (0.93 - 1.04) | 0.538 | 1.03 (0.94 - 1.12) | 0.540 | 1.01 (0.93 - 1.09) | 0.826 | 0.94 (0.86 - 1.03) | 0.173 | 0.94 (0.87 - 1.02) | 0.141 |
Smoking | Current |
1.24 (1.09 - 1.42)
|
0.002
|
1.23 (1.09 - 1.38)
|
0.001
|
1.25 (1.04 - 1.50)
|
0.017
|
1.21 (1.03 - 1.43)
|
0.019
|
1.23 (1.02 - 1.47)
|
0.031
|
1.19 (1.02 - 1.40)
|
0.033
|
Smoking | Ex | 1.07 (0.96 - 1.21) | 0.237 | 1.08 (0.98 - 1.20) | 0.101 | 1.02 (0.87 - 1.21) | 0.791 | 1.05 (0.91 - 1.21) | 0.489 | 1.12 (0.96 - 1.32) | 0.151 | 1.13 (0.99 - 1.30) | 0.081 |
DAS28 | Tertiles | 1.04 (0.98 - 1.11) | 0.226 | 1.02 (0.96 - 1.07) | 0.580 | 1.08 (0.99 - 1.19) | 0.087 | 1.04 (0.97 - 1.13) | 0.285 | 1.02 (0.93 - 1.11) | 0.711 | 0.99 (0.91 - 1.07) | 0.738 |
DAS28-P | Tertiles | 0.99 (0.93 - 1.05) | 0.719 | 0.98 (0.93 - 1.04) | 0.567 | 0.96 (0.88 - 1.05) | 0.410 | 0.98 (0.91 - 1.06) | 0.549 | 0.99 (0.91 - 1.08) | 0.876 | 1.00 (0.93 - 1.08) | 0.993 |
Duration | Tertiles | 0.98 (0.92 - 1.05) | 0.626 | 1.01 (0.95 - 1.06) | 0.841 |
0.87 (0.79 - 0.95)
|
0.002
|
0.89 (0.82 - 0.96)
|
0.004
| 1.09 (1.00 - 1.19) | 0.053 |
1.09 (1.01 - 1.17)
|
0.037
|
Serology | Positive | 1.04 (0.93 - 1.16) | 0.523 | 1.01 (0.92 - 1.11) | 0.830 | 0.94 (0.81 - 1.09) | 0.432 | 0.92 (0.81 - 1.05) | 0.213 | 1.09 (0.93 - 1.26) | 0.283 | 1.07 (0.94 - 1.21) | 0.344 |
Erosions | Positive | 0.93 (0.84 - 1.04) | 0.224 | 0.93 (0.85 - 1.03) | 0.151 | 0.96 (0.83 - 1.12) | 0.619 | 0.95 (0.84 - 1.09) | 0.482 | 0.93 (0.80 - 1.09) | 0.368 | 0.94 (0.82 - 1.07) | 0.324 |
Extra-articular manifestation | Yes |
1.17 (1.05 - 1.31)
|
0.004
|
1.17 (1.07 - 1.29)
|
0.001
| 1.08 (0.93 - 1.27) | 0.302 | 1.06 (0.93 - 1.22) | 0.386 |
1.33 (1.15 - 1.53)
|
<0.001
|
1.32 (1.16 - 1.50)
|
<0.001
|
Co-morbidity | Yes | 1.11 (1.00 - 1.24) | 0.059 |
1.14 (1.04 - 1.25)
|
0.005
| 1.12 (0.97 - 1.31) | 0.129 |
1.15 (1.01 - 1.31)
|
0.040
| 1.11 (0.95 - 1.28) | 0.182 | 1.13 (1.00 - 1.28) | 0.058 |
HAQ | Tertiles | 0.95 (0.89 - 1.01) | 0.097 | 0.97 (0.92 - 1.02) | 0.277 | 0.94 (0.86 - 1.02) | 0.143 | 0.95 (0.88 - 1.03) | 0.185 | 0.94 (0.86 - 1.02) | 0.138 | 0.97 (0.90 - 1.05) | 0.444 |
SF36-Vitality | Tertiles | 0.99 (0.92 - 1.06) | 0.771 | 0.98 (0.92 - 1.04) | 0.471 | 1.06 (0.96 - 1.17) | 0.248 | 1.05 (0.96 - 1.14) | 0.306 | 0.96 (0.87 - 1.06) | 0.402 | 0.96 (0.89 - 1.04) | 0.304 |
SF36-Mental Health | Tertiles | 1.02 (0.96 - 1.10) | 0.531 | 1.02 (0.96 - 1.08) | 0.540 | 1.00 (0.91 - 1.09) | 0.923 | 1.00 (0.91 - 1.08) | 0.900 | 1.02 (0.94 - 1.12) | 0.608 | 1.02 (0.94 - 1.11) | 0.587 |
SF36-Physical Function | Tertiles |
1.14 (1.06 - 1.22)
|
<0.001
|
1.15 (1.08 - 1.22)
|
<0.001
| 1.07 (0.97 - 1.18) | 0.171 | 1.08 (0.99 - 1.18) | 0.082 |
1.25 (1.14 - 1.38)
|
<0.001
|
1.24 (1.14 - 1.35)
|
<0.001
|
SF36-Bodily Pain | Tertiles |
1.13 (1.05 - 1.22)
|
0.002
|
1.12 (1.05 - 1.20)
|
<0.001
|
1.23 (1.10 - 1.36)
|
<0.001
|
1.22 (1.11 - 1.33)
|
<0.001
| 0.99 (0.90 - 1.10) | 0.885 | 1.04 (0.95 - 1.14) | 0.389 |
Steroid | At baseline | 0.99 (0.88 - 1.11) | 0.796 | 0.96 (0.87 - 1.06) | 0.436 | 0.98 (0.83 - 1.15) | 0.777 | 0.93 (0.80 - 1.07) | 0.288 | 0.96 (0.81 - 1.13) | 0.613 | 0.94 (0.82 - 1.09) | 0.380 |
Methotrexate | At baseline |
0.69 (0.61 - 0.78)
|
<0.001
|
0.70 (0.63 - 0.78)
|
<0.001
|
0.73 (0.61 - 0.87)
|
<0.001
|
0.70 (0.60 - 0.82)
|
<0.001
|
0.60 (0.50 - 0.71)
|
<0.001
|
0.58 (0.50 - 0.67)
|
<0.001
|
Sulphasalazine | At baseline |
0.74 (0.63 - 0.86)
|
<0.001
|
0.74 (0.65 - 0.84)
|
<0.001
| 0.85 (0.69 - 1.04) | 0.111 |
0.81 (0.68 - 0.97)
|
0.024
|
0.61 (0.49 - 0.77)
|
<0.001
|
0.66 (0.55 - 0.80)
|
<0.001
|
Lefunomide | At baseline | 1.07 (0.88 - 1.30) | 0.524 | 1.01 (0.85 - 1.19) | 0.928 |
1.36 (1.05 - 1.75)
|
0.019
| 1.19 (0.95 - 1.49) | 0.133 | 0.86 (0.65 - 1.13) | 0.267 | 0.88 (0.69 - 1.11) | 0.262 |
Hydroxychloroquine | At baseline |
0.82 (0.68 - 0.98)
|
0.032
|
0.85 (0.73 - 1.00)
|
0.046
| 0.87 (0.67 - 1.12) | 0.273 | 0.90 (0.73 - 1.13) | 0.364 | 0.79 (0.61 - 1.04) | 0.134 | 0.88 (0.71 - 1.10) | 0.274 |
Gold | At baseline |
0.62 (0.41 - 0.95)
|
0.026
| 0.70 (0.48 - 1.01) | 0.055 | 0.60 (0.32 - 1.10) | 0.097 | 0.68 (0.40 - 1.16) | 0.161 | 0.65 (0.37 - 1.14) | 0.613 | 0.66 (0.40 - 1.11) | 0.115 |