Background
Methods
Participants
Data source
Patients and follow-up
Drug retention and discontinuation
Serious adverse events (SAEs)
Statistical analysis
Results
Baseline characteristics of elderly RA patients who started TNF inhibitors
Total (n = 429) | Elderly patients (n = 107) | Younger patients (n = 322) | p-value | |
---|---|---|---|---|
Age, year
|
49.5 ± 13.6
|
66.1 ± 5.4
|
44.0 ± 10.6
|
<0.01
|
Sex, male
|
60 (14.0)
|
24 (22.4)
|
36 (11.2)
|
0.01
|
Disease duration, years
|
8.6 ± 6.8
|
10.0 ± 7.9
|
8.2 ± 6.4
|
0.03
|
First use of TNF inhibitor | 329 (76.7) | 83 (77.6) | 246 (76.4) | 0.91 |
Number of previous non-biologic DMARDs used
|
4.1 ± 1.5
|
4.4 ± 1.7
|
3.9 ± 1.5
|
0.01
|
Concomitant MTX use | 311 (72.5) | 79 (73.8) | 232 (72.1) | 0.75 |
Concomitant MTX dosage, mg/week | 14.0 ± 3.8 | 13.6 ± 3.5 | 14.2 ± 3.6 | 0.20 |
Concomitant glucocorticoid use | 331 (77.2) | 83 (77.6) | 248 (77.0) | 1.00 |
Concomitant glucocorticoid dosage, mg/day | 6.0 ± 4.1 | 6.5 ± 5.8 | 5.8 ± 3.4 | 0.34 |
RF positivity | 327 (76.2) | 84 (78.5) | 243 (75.5) | 0.59 |
DAS28-ESR* | 6.0 ± 0.9 | 6.0 ± 0.8 | 6.0 ± 0.9 | 0.46 |
Comorbid conditions | ||||
Cardiovascular disease
|
12 (2.8)
|
8 (7.5)
|
4 (1.2)
|
<0.01
|
Pulmonary disease
a
|
23 (5.4)
|
17 (15.9)
|
6 (1.9)
|
<0.01
|
Previous history of pulmonary tuberculosis | 41 (9.6) | 14 (13.1) | 27 (8.4) | 0.21 |
Gastrointestinal disease | 138 (32.2) | 41 (38.3) | 97 (30.1) | 0.15 |
Hepatobiliary diseaseb | 46 (10.7) | 13 (12.2) | 33 (10.3) | 0.71 |
Diabetes mellitus
|
41 (9.6)
|
20 (18.7)
|
21 (6.5)
|
<0.01
|
Malignancy | 18 (4.2) | 7 (6.5) | 11 (3.4) | 0.17 |
Hypertension
|
95 (22.1)
|
50 (46.7)
|
45 (14.0)
|
<0.01
|
Thyroid disease | 26 (6.1) | 7 (6.5) | 19 (5.9) | 0.99 |
Renal diseasec | 10 (2.3) | 1 (0.9) | 9 (2.8) | 0.46 |
Biologic agents | ||||
Etanercept | 264 (61.5) | 72 (67.3) | 192 (59.6) | 0.34 |
Adalimumab | 113 (26.3) | 25 (23.4) | 88 (27.3) | |
Infliximab | 52 (12.1) | 10 (9.4) | 42 (13.0) |
Drug retention rate of TNF inhibitor in elderly patients
Total (n = 429) | Elderly patients (n = 107) | Younger patients (n = 322) | p value | |
---|---|---|---|---|
Number of discontinuations | 167 (38.9) | 35 (32.7) | 132 (41.0) | 0.16 |
Reason for discontinuation | 0.43 | |||
Adverse effect |
44 (26.4)
|
12 (34.3)
|
32 (24.2)
| |
Ineffectiveness |
64 (38.3)
|
9 (25.7)
|
55 (41.7)
| |
Patient need | 37 (22.2) | 9 (25.7) | 28 (21.2) | |
Good effectiveness | 7 (4.2) | 2 (5.7) | 5 (3.8) | |
Economic problem | 3 (1.8) | 1 (2.9) | 2 (1.5) | |
Operation or hospitalization | 4 (2.4) | 1 (2.9) | 3 (2.3) | |
Othera | 3 (1.8) | 1 (2.9) | 2 (1.5) | |
Unknown | 5 (3.0) | - | 5 (3.8) |
Total RA | Elderly patients | Young RA | ||||
---|---|---|---|---|---|---|
Adjusted HR (95 % CI) |
p
| Adjusted HR (95 % CI) |
p
| Adjusted HR (95 % CI) |
p
| |
Age at start of biologics | 1.00 (0.99 – 1.02) | 0.66 |
1.09 (1.02 – 1.16)
| <0.01 | 1.00 (0.99 – 1.02) | 0.64 |
Sex, female | 1.06 (0.65 – 1.74) | 0.81 | 1.81 (0.64 – 5.12) | 0.27 | 0.84 (0.47 – 1.49) | 0.55 |
Switcher vs. first user |
0.55 (0.35 – 0.86)
| <0.01 | 0.43 (0.16 – 1.22) | 0.11 |
0.57 (0.34 – 0.94)
| 0.03 |
Disease duration, per year |
0.97 (0.95 – 0.997)
| 0.03 | 0.96 (0.91 – 1.00) | 0.05 |
0.97 (0.94 – 0.997)
| 0.03 |
Biologics | ||||||
Etanercept | 1.00 | 1.00 | 1.00 | |||
Infliximab | 1.44 (0.92 – 2.27) | 0.11 | 0.43 (0.10 – 1.97) | 0.28 |
1.81 (1.11 – 2.95)
| 0.02 |
Adalimumab | 0.88 (0.59 – 1.32) | 0.54 | 0.72 (0.30 – 1.74) | 0.46 | 0.86 (0.54 – 1.37) | 0.53 |
Concomitant use of methotrexate | 0.72 (0.51 – 1.01) | 0.06 |
0.44 (0.21 – 0.91)
| 0.03 | 0.91 (0.62 – 1.35) | 0.64 |
Concomitant glucocorticoid dosage | ||||||
<5 mg/day | 1.00 | 1.00 | 1.00 | |||
≥5 mg/day | 1.05 (0.76 – 1.46) | 0.75 | 1.18 (0.53 – 2.62) | 0.68 | 0.97 (0.67 – 1.41) | 0.89 |
Comorbiditya | 0.91 (0.64 – 1.29) | 0.59 |
0.37 (0.15 – 0.91)
| 0.03 | 1.04 (0.71 – 1.52) | 0.83 |
Safety of TNF inhibitors in elderly RA patients
System organ class allocation | Total (838 PYs) | Elderly patients (212 PYs) | Younger patients (626 PYs) | IRR (elderly patient/younger patients) |
---|---|---|---|---|
Total |
5.37 (3.92 – 7.19)
|
6.13 (3.27 – 10.49)
|
5.11 (3.50 – 7.22)
|
1.20 (0.63–2.29)
|
General disorders | 0.12 (0.00 – 0.66) | 0.47 (0.01 – 2.63) | – | |
Hypersensitivity | 0.24 (0.03 – 0.86) | – | 0.32 (0.04 – 1.15) | |
Hepatobiliary disorders | 0.48 (0.13 – 1.22) | 0.47 (0.01 – 2.63) | 0.48 (0.10 – 1.40) | 0.98 (0.10–9.46) |
Infections | 2.39 (1.46 – 3.69) | 2.36 (0.77 – 5.50) | 2.40 (1.34 – 3.95) | 0.98 (0.36–2.71) |
Injury |
0.60 (0.19 – 1.39)
|
0.94 (0.11 – 3.41)
|
0.48 (0.10 – 1.40)
|
1.97 (0.33–11.78)
|
Musculoskeletal and connective tissue disorders | 0.24 (0.03 – 0.86) | – | 0.32 (0.04 – 1.15) | |
Malignant | 0.95 (0.41 – 1.88) | 0.94 (0.11 – 3.41) | 0.96 (0.35 – 2.09) | 0.98 (0.20–4.88) |
Nervous system disorders | 0.12 (0.00 – 0.66) | 0.47 (0.01 – 2.36) | – | |
Respiratory, thoracic, and mediastinal disorders |
0.24 (0.03 – 0.86)
|
0.47 (0.01 – 2.36)
|
0.16 (0.00 – 0.89)
|
2.95 (0.18–47.21)
|