| Adverse event | Biological | Recommended dose anti-TNF vs placebo | High-dose anti-TNF vs placebo | ||||||||||
| Studies | N | Patient-years | Meta-analysis (OR) | Exposure-adjusted meta-analysis (RR) | Simple exposure-adjusted pooled (RR) | Studies | N | Patient-years | Meta-analysis (OR) | Exposure-adjusted meta-analysis (RR) | Simple exposure-adjusted pooled (RR) | ||
| Death | ADA | 6 | 2660 | 2406 | 2.04 (0.64 to 6.51) | 1.95 (0.61 to 6.21) | 2.86 (0.71 to 11.52) | 3 | 560 | 184 | 1.13 (0.18 to 7.30) | 1.18 (0.17 to 8.11) | 1.32 (0.17 to 10.04) |
| ETA | 6 | 2404 | 2164 | 2.34 (0.67 to 8.12) | 2.22 (0.66 to 7.46) | 2.16 (0.53 to 8.85) | 0 | NA | NA | NA | NA | N/A | |
| IFX | 5 | 1707 | 1164 | 0.62 (0.21 to 1.79) | 0.48 (0.17 to 1.40) | 0.36 (0.12 to 1.06) | 5 | 1535 | 1437 | 0.59 (0.23 to 1.5) | 0.64 (0.28 to 1.48) | 0.73 (0.29 to 1.82) | |
| Anti-TNF | 17 | 6771 | 5734 | 1.39 (0.74 to 2.62) | 1.23 (0.66 to 2.29) | 1.13 (0.57 to 2.27) | 8 | 2095 | 1621 | 0.68 (0.29 to 1.56) | 0.73 (0.34 to 1.56) | 0.78 (0.33 to 1.84) | |
| Serious adverse events | ADA | 4 | 1912 | 1814 | 1.12 (0.86 to 1.45)H | 0.75 (0.40 to 1.44)H | 1.05 (0.84 to 1.3) | 2 | 425 | 132 | Only 2 studies | Only 2 studies | 0.71 (0.4 to 1.24) |
| ETA | 5 | 1827 | 980 | 1.04 (0.73 to 1.47) | 0.96 (0.71 to 1.29) | 0.85 (0.62 to 1.18) | 0 | NA | NA | NA | NA | N/A | |
| IFX | 4 | 1664 | 1164 | 1.17 (0.86 to 1.59) | 0.98 (0.76 to 1.26) | 1.03 (0.80 to 1.33) | 4 | 1840 | 1427 | 1.09 (0.82 to 1.47) | 0.97 (0.55 to 1.71)H | 1.00 (0.78 to 1.29) | |
| Anti-TNF | 13 | 5403 | 3948 | 1.11 (0.94 to 1.32) | 0.94 (0.77 to 1.15)H | 1.00 (0.87 to 1.16) | 6 | 2265 | 1559 | 1.04 (0.80 to 1.36) | 0.84 (0.57 to 1.24)H | 0.92 (0.73 to 1.16) | |
| Serious infections | ADA | 6 | 2660 | 2406 | 1.53 (0.83 to 2.81) | 1.47 (0.79 to 2.71) | 1.41 (0.77 to 2.59) | 3 | 560 | 184 | 5.77 (0.90 to 36.91) | 5.16 (0.74 to 36.18) | 14.26 (1.18 to 171.8) |
| ETA | 5 | 1984 | 2072 | 0.89 (0.56 to 1.42) | 0.81 (0.52 to 1.27) | 0.86 (0.56 to 1.31) | 0 | NA | NA | NA | NA | NA | |
| IFX | 5 | 1707 | 1164 | 1.46 (0.86 to 2.47) | 1.19 (0.73 to 1.94) | 1.18 (0.74 to 1.90) | 5 | 1882 | 1437 | 1.89 (1.18 to 3.02) | 1.76 (0.70 to 4.43)H | 1.63 (1.04 to 2.55) | |
| Anti-TNF | 16 | 6351 | 5642 | 1.21 (0.89 to 1.63) | 1.07 (0.81 to 1.43) | 1.08 (0.81 to 1.43) | 8 | 2442 | 1621 | 2.07 (1.31 to 3.26) | 1.99(0.90 to 4.37)H | 1.83 (1.18 to 2.85) | |
| Lymphomas | ADA | 6 | 2660 | 2406 | 1.07 (0.28 to 4.09) | 1.06 (0.29 to 3.97) | 1.04 (0.14 to 7.95) | 3 | 560 | 184 | 1.00 (0.10 to 10.15) | 1.00 (0.10 to 10.42) | 1.00 (0.06 to 18.00) |
| ETA | 6 | 2407 | 1850 | 1.42 (0.27 to 7.61) | 1.43 (0.27 to 7.70) | 3.86 (0.24 to 62.21) | 0 | NA | NA | NA | NA | NA | |
| IFX | 5 | 1707 | 1164 | 1.42 (0.27 to 7.62) | 1.43 (0.28 to 7.29) | 2.50 (0.16 to 39.47) | 5 | 1873 | 1437 | 1.22 (0.21 to 7.13) | 1.16 (0.19 to 7.18) | 2.46 (0.15 to 40.24) | |
| Anti-TNF | 17 | 6756 | 5419 | 1.26 (0.52 to 3.06) | 1.26 (0.53 to 3.01) | 2.41 (0.37 to 15.59) | 8 | 2433 | 1621 | 1.14 (0.28 to 4.61) | 1.10 (0.26 to 4.62) | 1.54 (0.17 to 13.82) | |
| Non-cutaneous cancers and melanomas | ADA | 6 | 2660 | 2406 | 1.37 (0.49 to 3.89) | 1.34 (0.47 to 3.82) | 1.74 (0.52 to 5.85) | 3 | 560 | 184 | 2.38 (0.32 to 17.45) | 2.25 (0.29 to 17.31) | 4.32 (0.33 to 56.45) |
| ETA | 6 | 2405 | 1827 | 1.11 (0.42 to 2.96) | 0.95 (0.34 to 2.65) | 0.86 (0.34 to 2.22) | 0 | NA | NA | NA | NA | NA | |
| IFX | 5 | 1707 | 1164 | 1.70 (0.39 to 7.32) | 1.63 (0.37 to 7.07) | 3.48 (0.56 to 21.7) | 5 | 1883 | 1437 | 3.19 (0.79 to 12.93) | 3.44 (0.84 to 14.14) | 4.18 (0.69 to 25.54) | |
| Anti-TNF | 17 | 6772 | 5397 | 1.31 (0.69 to 2.48) | 1.21 (0.63 to 2.32) | 1.40 (0.69 to 2.83) | 8 | 2443 | 1621 | 2.91 (0.93 to 9.15) | 3.04 (0.95 to 9.68) | 5.31 (0.88 to 31.97) | |
| Non-melanoma skin cancers | ADA | 6 | 2453 | 2406 | 1.37 (0.49 to 3.89) | 0.66 (0.15 to 2.92) | 0.52 (0.05 to 4.99) | 3 | 560 | 184 | 0.60 (0.08 to 4.62) | 0.56 (0.07 to 4.28) | 0.28 (0.03 to 3.13) |
| ETA | 5 | 1981 | 1465 | 1.03 (0.38 to 2.77) | 2.02 (0.43 to 9.31) | 2.42 (0.39 to 15.06) | 0 | NA | NA | NA | NA | NA | |
| IFX | 4 | 982 | 867 | 1.70 (0.39 to 7.32) | 0.61 (0.11 to 3.42) | 0.34 (0.03 to 4.14) | 4 | 1159 | 1141 | 1.20 (0.25 to 5.87) | 0.91 (0.19 to 4.40) | 2.67 (0.40 to 17.77) | |
| Anti-TNF | 15 | 5416 | 4738 | 1.27 (0.67 to 2.42) | 1.01 (0.42 to 2.44) | 1.41 (0.41 to 4.91) | 7 | 1719 | 1325 | 0.93 (0.27 to 3.15) | 0.75 (0.21 to 2.60) | 1.33 (0.29 to 6.22) | |
H, Fixed effect method analysis determined to be heterogeneous using the a-prioi definition, random effects method shown. ADA, adalimumab; ETA, etanercept; IFX, infliximab; OR, odds ratio; RR, risk ratio; TNF, tumour necrosis factor.