Select cohort characteristics
| Methotrexate (n=6194) | TNF (n=3523) | SMD pre | SMD post | Non-TNF biologic/tsDMARD (n=1060) | SMD pre | SMD post | Total | |
| Age | 74.2±10.7 | 70.0±11.6 | −0.37 | −0.01 | 70.3±11.3 | −0.36 | −0.12 | 72.5±11.3 |
| Female | 4907 (79.2) | 2852 (81.0) | 0.04 | 0.01 | 867 (81.8) | 0.07 | 0.05 | 8626 (80.0) |
| Race | ||||||||
| White | 5040 (81.4) | 2648 (75.2) | −0.15 | −0.01 | 831 (78.4) | −0.07 | −0.06 | 8519 (79.0) |
| Black | 397 (6.4) | 252 (7.2) | 0.03 | 0.00 | 62 (5.8) | −0.02 | 0.06 | 711 (6.6) |
| Hispanic | 371 (6.0) | 343 (9.7) | 0.14 | 0.00 | 68 (6.4) | 0.02 | −0.02 | 782 (7.3) |
| Other/unknown | 386 (6.2) | 280 (7.9) | 0.07 | 0.02 | 99 (9.3) | 0.12 | 0.05 | 765 (7.1) |
| Disability | ||||||||
| Not disabled | 4250 (68.6) | 1977 (56.1) | −0.26 | 0.00 | 602 (56.8) | −0.25 | −0.09 | 6829 (63.4) |
| Disabled age <65 | 872 (14.1) | 868 (24.6) | 0.27 | 0.00 | 236 (22.3) | 0.21 | 0.04 | 1976 (18.3) |
| Disabled age ≥65 | 1072 (17.3) | 678 (19.2) | 0.05 | 0.00 | 222 (20.9) | 0.09 | 0.07 | 1972 (18.3) |
| Year 2011–2015* | 3307 (53.4) | 1849 (52.5) | −0.04 | 0.01 | 749 (70.7) | 0.39 | 0.22 | 5905 (54.8) |
| Surgery type | ||||||||
| Hip fracture | 2213 (35.7) | 1050 (29.8) | −0.13 | −0.01 | 322 (30.4) | −0.11 | −0.05 | 3585 (33.3) |
| Cholecystectomy elective | 210 (3.4) | 151 (4.3) | 0.05 | −0.01 | 36 (3.4) | 0.00 | −0.02 | 397 (3.7) |
| Cholecystectomy non-elective | 1020 (16.5) | 660 (18.7) | 0.06 | 0.02 | 191 (18.0) | 0.04 | 0.00 | 1871 (17.4) |
| Hysterectomy | 397 (6.4) | 349 (9.9) | 0.13 | 0.00 | 80 (7.5) | 0.05 | 0.02 | 826 (7.7) |
| Hernia elective | 282 (4.6) | 151 (4.3) | −0.01 | 0.00 | 47 (4.4) | −0.01 | 0.03 | 480 (4.5) |
| Hernia non-elective | 216 (3.5) | 148 (4.2) | 0.04 | 0.00 | 30 (2.8) | −0.04 | 0.03 | 394 (3.7) |
| Appendectomy | 180 (2.9) | 129 (3.7) | 0.04 | 0.01 | 48 (4.5) | 0.09 | 0.01 | 357 (3.3) |
| Colectomy elective | 160 (2.6) | 69 (2.0) | −0.04 | −0.01 | 25 (2.4) | −0.01 | 0.00 | 254 (2.4) |
| Colectomy non-elective | 251 (4.1) | 135 (3.8) | −0.01 | 0.01 | 60 (5.7) | 0.08 | −0.01 | 446 (4.1) |
| CABG elective | 229 (3.7) | 155 (4.4) | 0.04 | 0.00 | 37 (3.5) | −0.01 | −0.01 | 421 (3.9) |
| CABG non-elective | 523 (8.4) | 252 (7.2) | −0.05 | 0.00 | 83 (7.8) | −0.02 | −0.04 | 858 (8.0) |
| Valve elective | 273 (4.4) | 133 (3.8) | −0.03 | 0.01 | 47 (4.4) | 0.00 | 0.03 | 453 (4.2) |
| Valve non-elective | 240 (3.9) | 141 (4.0) | 0.01 | 0.00 | 54 (5.1) | 0.06 | 0.08 | 435 (4.0) |
| Average glucocorticoid dose | ||||||||
| None | 3248 (52.4) | 1984 (56.3) | 0.08 | 0.00 | 488 (46.0) | −0.13 | 0.00 | 5720 (53.1) |
| ≤5 | 1851 (29.9) | 962 (27.3) | −0.06 | −0.01 | 324 (30.6) | 0.02 | −0.04 | 3137 (29.1) |
| 5–10 | 837 (13.5) | 442 (12.5) | −0.03 | 0.00 | 180 (17.0) | 0.10 | 0.01 | 1459 (13.5) |
| >10 | 258 (4.2) | 135 (3.8) | −0.02 | 0.01 | 68 (6.4) | 0.10 | 0.05 | 461 (4.3) |
| Previous biologics | ||||||||
| 0 | 5486 (88.6) | 2949 (83.7) | −0.14 | −0.02 | 390 (36.8) | −1.27 | −0.11 | 8825 (81.9) |
| 1 | 543 (8.8) | 448 (12.7) | 0.13 | 0.01 | 461 (43.5) | 0.86 | 0.07 | 1452 (13.5) |
| >1 | 165 (2.7) | 126 (3.6) | 0.05 | 0.03 | 209 (19.7) | 0.56 | 0.05 | 500 (4.6) |
| NSAIDs | 1600 (25.8) | 957 (27.2) | 0.03 | 0.00 | 255 (24.1) | −0.04 | −0.03 | 2812 (26.1) |
| Opioids | 2986 (48.2) | 1860 (52.8) | 0.09 | 0.00 | 612 (57.7) | 0.19 | 0.15 | 5458 (50.6) |
| Charlson Score | 3.0+/-2.8 | 2.7+/-2.8 | −0.09 | 0.01 | 3.1+/-2.9 | 0.04 | 0.03 | 2.9+/-2.8 |
| Extra-articular RA | 127 (2.1) | 92 (2.6) | 0.04 | 0.00 | 42 (4.0) | 0.11 | 0.08 | 261 (2.4) |
| Diabetes | 1541 (24.9) | 834 (23.7) | −0.03 | 0.00 | 288 (27.2) | 0.05 | 0.02 | 2663 (24.7) |
| Asthma/COPD | 1346 (21.7) | 717 (20.4) | −0.03 | 0.00 | 208 (19.6) | −0.05 | 0.03 | 2271 (21.1) |
| Hospitalisations past year | ||||||||
| 0 | 3925 (63.4) | 2365 (67.1) | 0.08 | 0.00 | 698 (65.8) | 0.05 | −0.04 | 6988 (64.8) |
| 1–2 | 1454 (23.5) | 758 (21.5) | −0.05 | 0.00 | 231 (21.8) | −0.04 | 0.02 | 2443 (22.7) |
| >2 | 815 (13.2) | 400 (11.4) | −0.06 | 0.00 | 131 (12.4) | −0.02 | 0.02 | 1346 (12.5) |
| Hospitalised infection past year | 1062 (17.1) | 500 (14.2) | −0.08 | 0.00 | 153 (14.4) | −0.07 | 0.03 | 1715 (15.9) |
| Outpatient visits | 14.5±9.5 | 16.1±9.3 | 0.17 | 0.01 | 19.5±10.2 | 0.50 | 0.21 | 15.5±9.6 |
| Skilled nursing facility stay past year | 963 (15.5) | 313 (8.9) | −0.21 | −0.01 | 74 (7.0) | −0.27 | −0.05 | 1350 (12.5) |
Mean ± SD or N (%) shown. Full cohort characteristics shown in online supplementary table S2. Standardised mean differences (SMD) are shown compared with the methotrexate-treated group, either before (pre) or after (post) inverse probability weighting, with SMD >0.1 indicating imbalance. Characteristics with SMD >0.1 after weighting are shown in bold and were added as covariates to weighted models.
*Year modelled as continuous and SMD shown indicates standardised difference in means across groups.
CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; NSAID, nonsteroidal anti-inflammatory drugs; RA, rheumatoid arthritis; TNF, tumour necrosis factor; tsDMARD, targeted synthetic disease-modifying antirheumatic drugs.