Table 1. Published reports on the frequencies of hypersensitivity reactions to biologics.
| Biologic | Target | Author | Year | HSR | IR | ISR | Urticaria | Anaphylaxis |
|---|---|---|---|---|---|---|---|---|
| Omalizumab | IgE | Cox et al. [136] Di Bona et al. [137] FDA [138]a FDA [138]b EMA [139] |
2007 2017 2019 2019 2019 |
< 0.2 – – – – |
– 3.4 12.0 – 45.0 0.6 – 2.7 1.0 – 10.0 |
– 1.0 0.2 – 0.1 – 1.0 |
0.09 0 0.1 – 0.2 |
|
| Ligelizumab | Cε3 domain of IgE | Gauvreau et al. [140] Maurer et al. [141] |
2016 2019 |
– – |
12.5–25.0 4.0–7.0 |
0 – |
0 0 |
|
| Mepolizumab | IL-5 | Pavord et al. [142] Lugogo et al. [143] Khatri et al. [144] FDA [145] EMA [146] Chapman et al. [147] |
2012 2016 2019 2019 2019 2019 |
≤ 1.0 < 1.0 2.0 1.0 – 4.0 1.0 – 10.0 < 1.0 |
5.0 – 12.0 < 1.0 – – 1.0–10.0 – |
– 3.0 12.0 8.0 – 15.0 1.0 – 10.0 3.0 |
– – – – – < 1.0 |
0 0 0 – 0.1 – 0.01 0 |
| Reslizumab | IL-5 | Castro et al. [60] Murphy et al. [148] FDA [149] EMA [150] Bernstein et al. [151] |
2015 2017 2019 2019 2020 |
– < 1.0 – 0.19 0 |
– < 1.0 – 0.19 – |
1.0 – 2.0 < 1.0 – – 6.0 – 11.0 |
– < 1.0 – – – |
< 1.0 0 0.3 0.19 – |
| Benralizumab | IL-5Rα | Castro et al. [152] Park et al. [153] Liu et al. [154] FDA [155] EMA [156] Bourdin et al. [157] |
2014 2019 2019 2019 2019 2019 |
– – – 3.0 1.0 – 10.0 0 – 3.2 |
16.0 0 2.6 – 17.5 2.2 2.2 3.2 – 6.5 |
– 0 – 2.0 – 3.0 – – |
– – – 3.0 ? – |
|
| Dupilumab | IL-4Rα | Ou et al. [158] EMA [159] FDA [160] |
2018 2019 2020 |
– 3.0 – 4.3 < 1.0 |
13.2 16.0 – 20.1 10.0 |
– 0.5 – 1.3 < 1.0 |
– 0.2 < 1.0 |
|
| Lanadelumab | Plasma kallikrein | FDA [161] EMA [162] |
2018 2020 |
1.0 1.2 |
45 – 57.0 52.4 |
– – |
– – |
|
| Lebrikizumab | IL-13 | Hanania et al. [163] Hanania et al. [164] Simpson et al. [117] Korenblat et al. [165] |
2015 2016 2018 2018 |
0 – 0.9 – – – |
11.1 – 20.5 6 – 10.0 1.3 2.9 |
– – – – |
0 – 0.9 < 1.0 0 1.0 |
|
| Tralokinumab | IL-13 | Wollenberg et al. [166] Panettieri et al. [167] Busse et al. [168] Carlsson et al. [169] |
2019 2018 2019 2019 |
– – –13.2 – 25.9 |
5.2 4.0 – 5.4 15.7 – |
– – – < 1.0 |
– 0 0 0 |
|
| Secukinumab | IL-17A | EMA [170] Blauvelt [171] Deodhar et al. [172] FDA [173] EMA [174] Grace et al. [175] |
2015 2016 2019 2020 2020 2020 |
6.5–11.2 – 2.4 – – – |
5.6 0.7 0.8 – 1.3 – – 25.0 |
< 1.0 – – 0.6 – 1.2 0.1 – 1.0 – |
0 – – – < 0.1 – |
|
| Fezakinumab | IL-22 | – | – | – | – | – | – | – |
| Nemolizumab | IL-31Rα | Nemoto et al. [176] Kabashima et al. [120] Silverberg et al. [177] Ständer et al. [178] |
2016 2018 2020 2020 |
– – – – |
– – – – |
– 2.0 1.8 – 3.5 3.0 |
– 2.0–6.0 – – |
0 – – – |
| Etokimab | IL-33 | Chen et al. [121] Chinthrajah et al. [179] |
2019 2019 |
– – |
– – |
25.0 26.7 |
16.7 6.7 |
– 0 |
| Ustekinumab | IL-12/IL-23 | Ghosh et al. [180] FDA [181] EMA [182] |
2019 2020 2020 |
< 1.0 0.08 0.1 – 1.0 |
0.1 – 0.1 |
– 1.0 – 2.0 0.1 – 1.0 |
< 1.0 < 1.0 – |
0 0.1 0.01 – 0.1 |
aResults of clinical studies with asthma in FDA 2019 label; bresults of pooled Chronic Idiopathic Urticaria trials in FDA 2019 label. HSR = hypersensitivity reaction; IR = infusion reaction, substance-specific; ISR = injection-site-reaction.