Table 2.
AESI numbers reported, rates per 100 patient years and RRs. For ETA, ADA, GOL, INF, TOC, ABA (both monotherapy and combination with MTX), the relative risk was calculated against all other biologics of this group. For TNF, the RR was calculated versus ABA+TOC. For MTX, the RR was calculated against all biologics. Patients may have multiple therapies, and AESIs may be counted under several therapies. AESI categories with at least three events are reported in this table
| Total n | ETA | ADA | GOL | INF | TNFi | TOC | ABA | MTX | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Patients (n) | 3873 | 2339 | 828 | 86 | 63 | 215 | 91 | 1404 | ||
| Numbers of all AESI categories | ||||||||||
| Total SAE (n) |
N Rate RR |
184 |
109 2.02 (1.68‐2.44) 0.78 (0.56‐1.08) |
27 1.86 (1.27‐2.71) 0.82 (0.54‐1.24) |
5 5.32 (2.21‐12.77) 2.48 (1.02‐6.04) |
8 7.39 (3.70‐14.78) 3.51 (1.72‐7.14) |
149 2.12 (1.80‐2.48) 0.64 (0.37‐1.11) |
10 3.27 (1.76‐6.08) 1.53 (0.81‐2.90) |
4 3.39 (1.27‐9.04) 1.57 (0.58‐4.23) |
21 0.66 (0.43‐1.01) 0.30 (0.19‐0.48) |
| Multiple SAEs | 6 | |||||||||
| Total AESI (n) |
N Rate RR |
758 |
362 6.72 (6.06‐7.45) 0.49 (0.42‐0.57) |
175 12.04 (10.38‐13.96) 1.53 (1.28‐1.82) |
23 24.45 (16.25‐36.80) 2.88 (1.90‐4.37) |
22 20.33 (13.39‐30.87) 2.39 (1.56‐3.65) |
576 8.18 (7.54‐8.87) 0.47 (0.37‐0.61) |
54 17.66 (13.52‐23.05) 2.12 (1.61‐2.81) |
13 11.02 (6.40‐18.98) 1.27 (0.74‐2.21) |
109 3.43 (2.85‐4.14) 0.40 (0.32‐0.48) |
| AESI categories with more than 2 reports | ||||||||||
| AESI (n) | 755 | 359 | 175 | 23 | 22 | 573 | 54 | 13 | 109 | |
| Multiple AESIs | 25 | 9 | 10 | 2 | 16 | 3 | 1 | |||
| Exposure years | 5387 | 1454 | 94 | 108 | 7043 | 306 | 118 | 3174 | ||
| Anaphylaxis |
N Rate RR |
21 |
4 0.07 (0.03‐0.20) 0.08 (0.03‐0.23) |
5 0.34 (0.14‐0.83) 1.09 (0.41‐2.92) |
0 |
5 4.62 (1.92‐11.10) 17.89 (6.68‐47.92) |
14 0.20 (0.12‐0.34) 0.08 (0.04‐0.19) |
7 2.29 (1.09‐4.80) 9.64 (4.00‐23.25) |
3 2.54 (0.82‐7.89) 8.90 (2.66‐29.84) |
2 0.06 (0.02‐0.25) 0.20 (0.05‐0.83) |
| Bleeding event |
N Rate RR |
9 |
3 0.06 (0.02‐0.17) 0.29 (0.06‐1.29) |
3 0.21 (0.07‐0.64) 3.10 (0.69‐13.86) |
0 | 0 |
6 0.09 (0.04‐0.19) 0.36 (0.04‐3.00) |
0 |
1 0.85 (0.12‐6.02) 10.39 (1.25‐86.27) |
2 0.06 (0.02‐0.25) 0.67 (0.14‐3.24) |
| Inflammatory bowel disease |
N Rate RR |
20 |
17 0.32 (0.20‐0.51) 2.19 (0.64‐7.46) |
2 0.14 (0.03‐0.55) 0.46 (0.11‐1.98) |
0 |
1 0.92 (0.13‐6.56) 3.58 (0.48‐26.73) |
20 0.28 (0.18‐0.44) |
0 | 0 | 0 |
| Cytopenia |
N Rate RR |
59 |
30 0.56 (0.39‐0.80) 0.68 (0.38‐1.24) |
4 0.28 (0.10‐0.73) 0.38 (0.14‐1.07) |
0 |
1 0.92 (0.13‐6.56) 1.48 (0.20‐10.72) |
35 0.50 (0.36‐0.69) 0.18 (0.09‐0.34) |
12 3.92 (2.23‐6.91) 8.03 (4.17‐15.46) |
0 |
12 0.38 (0.21‐0.67) 0.60 (0.32‐1.13) |
| Hepatic event |
N Rate RR |
41 |
15 0.28 (0.17‐0.46) 0.39 (0.19‐0.79) |
8 0.55 (0.28‐1.10) 1.50 (0.67‐3.38) |
0 |
1 0.92 (0.13‐6.56) 2.34 (0.32‐17.21) |
24 0.34 (0.23‐0.51) 0.24 (0.10‐0.59) |
5 1.63 (0.68‐3.93) 4.68 (1.79‐12.23) |
1 0.85 (0.12‐6.02) 2.15 (0.29‐15.77) |
11 0.35 (0.19‐0.63) 0.86 (0.43‐1.72) |
| Medically important infection |
N Rate RR |
101 |
58 1.08 (0.83‐1.39) 0.86 (0.54‐1.37) |
17 1.17 (0.73‐1.88) 1.05 (0.62‐1.79) |
5 5.32 (2.21‐12.77) 4.96 (2.01‐12.25) |
1 0.92 (0.13‐6.56) 0.82 (0.11‐5.89) |
81 1.15 (0.92‐1.43) 1.62 (0.51‐5.14) |
3 0.98 (0.32‐3.04) 0.87 (0.27‐2.75) |
0 |
20 0.63 (0.41‐0.98) 0.56 (0.34‐0.91) |
| Suspected malignancy |
N Rate RR |
7 |
3 0.06 (0.02‐0.17) 0.58 (0.10‐3.47) |
0 | 0 |
2 1.85 (0.46‐7.39) 45.33 (7.57‐271.3) |
5 0.07 (0.03‐0.17) |
0 | 0 |
3 0.09 (0.03‐0.29) 1.41 (0.34‐5.91) |
| Depression/ Suicidality |
N Rate RR |
21 |
11 0.20 (0.11‐0.37) 0.71 (0.26‐1.91) |
3 0.21 (0.07‐0.64) 0.89 (0.25‐3.09) |
0 | 0 |
14 0.20 (0.12‐0.34) 0.28 (0.08‐0.98) |
2 0.65 (0.16‐2.61) 3.12 (0.71‐13.65) |
1 0.85 (0.12‐6.02) 3.89 (0.52‐29.37) |
5 0.16 (0.07‐0.38) 0.69 (0.26‐1.88) |
| Pregnancy |
N Rate RR |
6 |
4 0.07 (0.03‐0.20) 0.77 (0.14‐4.22) |
2 0.14 (0.03‐0.55) 2.07 (0.38‐11.29) |
0 | 0 |
6 0.09 (0.04‐0.19) |
0 | 0 |
1 0.03 (0.00‐0.22) 0.39 (0.05‐3.26) |
| Thrombosis |
N Rate RR |
3 | 0 |
3 0.21 (0.07‐0.64) |
0 | 0 |
3 0.04 (0.01‐0.13) |
0 | 0 | 0 |
| Inefficacy |
N Rate RR |
112 |
57 1.06 (0.82‐1.37) 0.40 (0.28‐0.58) |
25 1.72 (1.16‐2.55) 1.19 (0.76‐1.85) |
8 8.51 (4.25‐17.01) 6.03 (2.94‐12.38) |
1 0.92 (0.13‐6.56) 0.61 (0.09‐4.39) |
89 1.26 (1.03‐1.56) 0.23 (0.15‐0.37) |
19 6.21 (3.96‐9.74) 4.78 (2.92‐7.84) |
2 1.70 (0.42‐6.78) 1.13 (0.28‐4.59) |
2 0.06 (0.02‐0.25) 0.04 (0.01‐0.17) |
| Hypertension |
N Rate RR |
8 |
4 0.07 (0.03‐0.20) 0.51 (0.12‐2.30) |
3 0.21 (0.07‐0.64) 3.10 (0.69‐13.86) |
0 | 0 |
7 0.10 (0.05‐0.21) |
0 | 0 |
1 0.03 (0.00‐0.22) 0.34 (0.04‐2.73) |
| Vasculitis |
N Rate RR |
3 |
3 0.06 (0.02‐0.17) |
0 | 0 | 0 |
3 0.04 (0.01‐0.13) |
0 | 0 |
1 0.03 (0.00‐0.22) 0.78 (0.08‐7.54) |
| Evolving autoimmune disease (including psoriasis) |
N Rate RR |
27 |
6 0.11 (0.05‐0.25) 0.11 (0.04‐0.26) |
14 0.96 (0.57‐1.63) 4.14 (1.97‐8.68) |
2 2.13 (0.53‐8.50) 6.03 (1.43‐25.40) |
1 0.92 (0.13‐6.56) 2.52 (0.34‐18.53) |
23 0.33 (0.22‐0.49) 0.28 (0.11‐0.73) |
2 0.65 (0.16‐2.61) 1.80 (0.43‐7.59) |
3 2.54 (0.82‐7.89) 7.48 (2.26‐24.77) |
1 0.03 (0.00‐0.22) 0.08 (0.01‐0.62) |
| Psoriasis |
N Rate RR |
17 |
2 0.04 (0.01‐0.15) 0.05 (0.01‐0.21) |
10 0.69 (0.37‐1.28) 5.17 (2.04‐13.10) |
1 1.06 (0.15‐7.55) 4.61 (0.61‐34.65) |
1 0.92 (0.13‐6.56) 4.00 (0.53‐30.06) |
14 0.20 (0.12‐0.34) 0.21 (0.07‐0.64) |
1 0.33 (0.05‐2.32) 1.38 (0.18‐10.35) |
3 2.54 (0.82‐7.89) 12.46 (3.61‐43.05) |
0 |
|
Uveitis, Iridozyclitis manifestation |
N Rate RR |
78 |
53 0.98 (0.75‐1.29) 2.27 (1.12‐4.61) |
8 0.55 (0.28‐1.10) 0.61 (0.29‐1.29) |
0 | 0 |
58 0.82 (0.64‐1.07) 0.87 (0.32‐2.40) |
0 |
1 0.85 (0.12‐6.02) 1.02 (0.14‐7.37) |
21 0.66 (0.43‐1.01) 0.80 (0.49‐1.31) |
| Uveitis flare |
N Rate RR |
153 |
58 1.08 (0.83‐1.39) 0.27 (0.19‐0.38) |
64 4.40 (3.45‐5.63) 3.44 (2.47‐4.79) |
7 7.44 (3.55‐15.61) 4.09 (1.92‐8.75) |
8 7.39 (3.70‐14.78) 4.09 (2.00‐8.35) |
136 1.93 (1.63‐2.28) 1.64 (0.67‐4.00) |
3 0.98 (0.32‐3.04) 0.51 (0.16‐1.60) |
1 0.85 (0.12‐6.02) 0.45 (0.06‐3.18) |
14 0.44 (0.26‐0.74) 0.23 (0.13‐0.40) |
| Uveitis all |
N Rate RR |
231 |
111 2.06 (1.71‐2.48) 0.47 (0.35‐0.61) |
72 4.95 (3.93‐6.24) 2.27 (1.71‐3.03) |
7 7.44 (3.55‐15.61) 2.80 (1.32‐5.95) |
8 7.39 (3.70‐14.78) 2.79 (1.38‐5.66) |
194 2.75 (2.39‐3.17) 1.30 (0.66‐2.53) |
3 0.98 (0.32‐3.04) 0.35 (0.11‐1.10) |
2 1.70 (0.42‐6.78) 0.62 (0.15‐2.50) |
35 1.10 (0.79‐1.54) 0.41 (0.28‐0.58) |
| Herpes Zoster |
N Rate RR |
35 |
22 0.41 (0.27‐0.62) 0.94 (0.43‐2.05) |
6 0.41 (0.19‐0.92) 0.99 (0.41‐2.42) |
1 1.06 (0.15‐7.55) 2.61 (0.36‐19.16) |
1 0.92 (0.13‐6.56) 2.27 (0.31‐16.62) |
30 0.43 (0.30‐0.61) 1.81 (0.25‐13.24) |
1 0.33 (0.05‐2.32) 0.78 (0.11‐5.72) |
0 |
5 0.16 (0.07‐0.38) 0.38 (0.15‐0.98) |
| Varicella |
N Rate RR |
26 |
11 0.20 (0.11‐0.37) 0.53 (0.21‐1.32) |
8 0.55 (0.28‐1.10) 3.01 (1.21‐7.48) |
0 | 0 |
19 0.27 (0.17‐0.42) |
0 | 0 |
8 0.25 (0.13‐0.50) 0.99 (0.43‐2.26) |
Abbreviation: ABA, abatacept; ADA, adalimumab; AE, adverse event; AESI, AE of special interest; ETA, etanercept; GOL, golimumab; INF, infliximab; MTX, methotrexate; RR, risk ratio; SAE, serious adverse event; TNFi, tumor necrosis factor α inhibitor; TOC, tocilizumab.