TABLE 2.
Methotrexate (MTX) use in patients with rheumatoid arthritis (RA) with or without interstitial lung disease (ILD)
| Discovery |
Pooled replication |
Combined |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RA-ILD | RA-noILD | p-value | ORadj (95% CI) |
RA-ILD | RA-noILD | p-value | ORadj (95% CI) |
RA-ILD | RA-noILD | p-value | ORadj (95% CI) |
|
| MTX exposure duration# years | 4 (1–13) | 10 (4–16) | <0.0001 | 6 (2–15) | 15 (8–22) | <0.0001 | 6 (1–14) | 13 (7–21) | <0.0001 | |||
| Periods of MTX use at year of RA onset | 0.17 | 0.97 | 0.68 | |||||||||
| Unlikely | 6 (6.0) | 19 (11.5) | 25 (8.1) | 39 (7.7) | 31 (7.6) | 58 (8.6) | ||||||
| Less often | 18 (18.0) | 24 (14.5) | 51 (16.5) | 79 (15.6) | 69 (16.8) | 103 (15.3) | ||||||
| Often | 42 (42.0) | 81 (49.1) | 126 (40.6) | 213 (41.9) | 168 (41.0) | 294 (43.7) | ||||||
| Standard of care | 34 (34.0) | 41 (24.8) | 108 (34.8) | 177 (34.8) | 142 (34.6) | 218 (32.4) | ||||||
| MTX ever-use¶ | 60 (60.0) | 137 (83.0) | 0.022 | 0.46 (0.24–0.90) | 247 (79.7) | 485 (95.5) | 0.009 | 0.39 (0.19–0.79) | 307 (74.9) | 622 (92.4) | 0.0006 | 0.43 (0.26–0.69) |
| MTX cumulative dose g | 0.1 (0.0–3.1) | 2.2 (0.2–5.5) | <0.0001 | 1.5 (0.0–4.7) | 4.5 (1.3–7.8) | <0.0001 | 1.3 (0.0–4.2) | 3.9 (1.0–7.4) | <0.0001 | |||
Data are presented as median (interquartile range) or n (%), unless otherwise stated. For MTX ever-use, odds ratio (ORadj) p-values are adjusted for age at RA onset, sex, ever-smoking, biologic ever-use, MTX exposure duration and periods of MTX use at year of RA onset, and obtained by random-effects meta-analysis of pooled estimates over multiply imputed datasets. p-values are unadjusted for MTX exposure duration, periods of MTX use at year of RA onset and MTX cumulative dose. RA-ILD: patients with RA-associated ILD; RA-noILD: RA patients without ILD.
to avoid any bias resulting in MTX withdrawal secondary to ILD co-occurrence in patients with RA, the MTX exposure for patients with RA-ILD was established during the period before the diagnosis of ILD;
UK excluded from the pooled replication and combined analyses.