Table 1. Frequency of hypersensitivity reaction to biologics.
| Biologic | Target | Author | Year |
HSR
% |
IR
% |
ISR
% |
Urticaria
% |
Anaphylaxis
% |
|---|---|---|---|---|---|---|---|---|
| Adalimumab | TNF-α | Puxeddu et al. [243] | 2012 | 3.5 | – | 1.5 | 1.5 | 0 |
| Tarkiainen et al. [244] | 2015 | 18.1 | 17.0 | – | – | |||
| EMA [245] | 2023 | 1.0 – 10.0 | 12.9 | 1.0 – 10.0 | 0.01 – 0.1 | |||
| FDA [246] | 2023 | 6.0 | 5.0 – 20.0 | 6.0 | – | |||
| Benralizumab | IL-5R | Castro et al. [247] | 2014 | – | 16.0 | – | – | |
| Park et al. [248] | 2019 | – | 0 | 0 – 2.0 | – | |||
| Liu et al. [249] | 2019 | – | 2.6–17.5 | – | – | |||
| FDA [250] | 2019 | 3.0 | 2.2 | 3.0 | 3.0 | |||
| Bourdin et al. [251] | 2019 | 0 – 3.2 | 3.2 – 6.5 | – | – | |||
| EMA [252] | 2023 | up to 10.0 | 2.2 | up to 10.0 | – | |||
| Yamaguchi et al. [253] | 2024 | 0.3 | – | – | 0.3 | |||
| Brodalumab | IL-17RA | FDA [254] | 2017 | – | 1.5 | 1.0 | – | |
| Iznardo et al. [255] | 2020 | < 1.0 | 1.8 | – | – | |||
| Kim et al. [256] | 2023 | – | 1.3 | – | – | |||
| EMA [257] | 2023 | – | 1.0 – 10.0 | – | 0.01 – 0.1 | |||
| Certolizumab | TNFα | FDA [258] | 2022 | – | 1.7 – 3.2 | – | – | |
| EMA [259] | 2023 | – | 1.0 – 10.0 | – | 0.01 – 0.1 | |||
| Kim et al. [256] | 2023 | – | 3.9 | – | – | |||
| Dupilumab | IL-4Rα | Ou et al. [260] | 2018 | – | 13.2 | – | – | |
| Halling et al [261] | 2021 | – | 5.3 | – | – | |||
| EMA [262] | 2023 | – | 1.0 – 10.0 | – | 0.01 – 0.1 | |||
| Kim et al. [256] | 2023 | – | 11.3 | – | – | |||
| FDA [263] | 2024 | < 1.0 | 6.0 – 38.0 | < 1.0 | < 1.0 | |||
| Simpson et al. [264] | 2024 | – | 3.0 | – | – | |||
| Yew et al. [265] | 2024 | – | 2.0 | 5.9 | – | |||
| Etanercept | TNF-α-RII | Puxeddu et. al. [243] | 2012 | 5.3 | – | 1.6 | 2.0 | 0.8 |
| Tarkiainen et al. [244] | 2015 | 11.3 | 7.5 | – | – | |||
| Girolomoni et al. [266] | 2018 | – | 10 – 49.0 | – | – | |||
| Codreanu et al. [267] | 2019 | – | 0.8 | – | 0.8 | |||
| FDA [268] | 2023 | < 1.0 | 15 – 43.0 | < 2.0 | < 2.0 | |||
| EMA [269] | 2024 | – | 13.6 – 36.0 | 0.1 – 1.0 | 0.01 – 0.1 | |||
| Etokimab | IL-33 | Chen et al. [270] | 2019 | – | – | 25.0 | 16.7 | – |
| Chinthrajah et al. [271] | 2019 | – | – | 26.7 | 6.7 | 0 | ||
| NCT03614923 - Eclipse [272] | 2022 | – | – | 2.8 – 5.7 | – | – | ||
| Fezakinumab | IL-22 | – | – | – | – | – | – | – |
| Garadacimab | FXIIa | Craigh et al. [273] | 2023 | 0 | – | 5.0 | – | 0 |
| Guselkumab | IL-23 | Langley et al. [274] | 2018 | 0 | 1.1 | 0 | ||
| FDA [275] | 2020 | – | 4.5 | < 1.0 | – | |||
| European Comission [276] | 2020 | 0.1 – 1.0 | 1.0 – 10.0 | 0.1 – 1.0 | 0.1 – 1.0 | |||
| Coates et al. [277] | 2021 | – | 1.8 | 0.4 | 0 | |||
| McInnes et al. [278] | 2022 | – | 2.5 – 2.7 | - | 0 | |||
| Danese et al. [279] | 2024 | 0 | 4.0 | - | 0 | |||
| Infliximab | TNF-α | Maggi et al. [280] | 2011 | – | 1.0 – 27.0 | – | – | – |
| Puxeddu et al. [243] | 2012 | 13.8 | – | 0 | 4.4 | 9.3 | ||
| Tarkiainen et al. [244] | 2015 | 34.1 | – | 1.9 | – | 1.9 | ||
| Lichtenstein et al. [281] | 2015 | – | 5.0 – 23.0 | – | 4.0 | – | ||
| Panés et al. [282] | 2019 | – | 13.0 | – | – | – | ||
| FDA [283] | 2023 | – | < 20.0 | – | < 1.0 | < 1.0 | ||
| EMA [284] | 2024 | – | > 10.0 | 1.0 – 10.0 | 1.0 – 10.0 | 0.1 – 1.0 | ||
| Ixekizumab | IL-17A | FDA [285] | 2022 | ≤ 0.1 | 17.0 | ≤ 0.1 | ≤ 0.1 | |
| EMA [286] | 2023 | – | > 10.0 | 0.1 – 1.0 | 0.01 – 0.1 | |||
| Kim et al. [256] | 2023 | – | 11.2 | – | – | |||
| Mastorino et al. [287] | 2023 | – | 3.1 | – | – | |||
| Ying et al. [288] | 2023 | 0.3 | 3.0 – 9.7 | 3.3 | – | |||
| Lanadelumab | Plasma kallikrein | FDA [289] | 2018 | 1.0 | 45.0 – 57.0 | – | – | |
| Craig et al. [290] | 2021 | – | 5.1 – 62.5 | – | – | |||
| Hide et al. [291] | 2023 | – | 50.0 | – | – | |||
| EMA [292] | 2024 | 1.2 | 52.4 | – | – | |||
| Lebrikizumab | IL-13 | Hanania et al. [293] | 2015 | 0 – 0.9 | 11.1 – 20.5 | – | 0 – 0.9 | |
| Hanania et al. [294] | 2016 | – | 6.0 – 10.0 | – | < 1.0 | |||
| Simpson et al. [295] | 2018 | – | 1.3 | – | 0 | |||
| Korenblat et al. [296] | 2018 | – | 2.9 | – | 1.0 | |||
| Austin [297] | 2020 | 0 | 7.0 | – | 0 | |||
| EMA [289] | 2023 | – | 2.6 | – | – | |||
| Paller et al. [299] | 2023 | – | 2.4 | 2.9 | 0 | |||
| Stein Gold et al. [300] | 2023 | 0 | 2.6 | – | 0 | |||
| Ligelizumab | Cε3 domain of IgE | Gauvreau et al. [301] | 2016 | – | 12.5 – 25.0 | 0 | 0 | |
| Maurer et al. [302] | 2019 | – | 4.0 – 7.0 | – | 0 | |||
| Wood et al. [239] | 2022 | – | – | 17.0 | 0.4 | |||
| Maurer et al. [303] | 2024 | 6.0 – 11.0 | 4.0 – 11.0 | – | < 1.0 | |||
| Mepolizumab | IL-5 | Pavord et al. [304] | 2012 | ≤ 1.0 | 5.0–12.0 | – | – | 0 |
| Lugogo et al. [305] | 2016 | < 1.0 | <1.0 | 3.0 | – | 0 | ||
| Leung et al. [306] | 2017 | 0 – 1.0 | 5.0 – 12.0 | 3.0 – 9.0 | 4.0 – 16.0 | 0.002 | ||
| Khatri et al. [307] | 2019 | 2.0 | – | 12.0 | – | 0 | ||
| Chapman et al. [308] | 2019 | < 1.0 | – | 3.0 | < 1.0 | 0 | ||
| EMA [309] | 2022 | 1.9 – 3.0 | – | 6.0 – 7.0 | – | 0 | ||
| FDA [310] | 2023 | 1.0 – 4.0 | 2.0 – 15.0 | – | – | |||
| Ishii et al. [311] | 2023 | < 1.0 | – | – | < 1.0 | |||
| Nemolizumab | IL-31Rα | Nemoto et al. [312] | 2016 | – | – | – | 0 | |
| Kabashima et al. [313] | 2018 | – | 2.0 | 2.0 – 6.0 | – | |||
| Silverberg et al. [314] | 2020 | – | 1.8 – 3.5 | – | – | |||
| Ständer et al. [315] | 2020 | – | 3.0 | – | – | |||
| Kabashima et al. [185] | 2022 | – | < 1.0 | – | – | |||
| Igarashi et al. [316] | 2023 | – | 2.2 | – | – | |||
| Omalizumab | IgE | Cox et al. [317] | 2007 | < 0.2 | – | – | 0.09 | |
| Di Bona et al. [318] | 2017 | – | 3.4 | 1.0 | 0 | |||
| FDA [319]a | 2023 | – | 12.0 – 45.0 | 0.2 | 0.1 | |||
| FDA [319]b | 2023 | – | 0.6 – 2.7 | – | – | |||
| EMA [320] | 2023 | – | 2.7 | 0.1–1.0 | 0.2 | |||
| Kim et al. [256] | 2023 | – | 4.5 | – | – | |||
| Reslizumab | IL-5 | Castro et al. [321] | 2015 | – | – | 1.0 – 2.0 | – | < 1.0 |
| Murphy et al. [322] | 2017 | < 1.0 | < 1.0 | < 1.0 | < 1.0 | 0 | ||
| FDA [323] | 2019 | – | – | – | – | 0.3 | ||
| Virschow et al. [324] | 2020 | – | – | – | – | < 1.0 | ||
| Bernstein et al. [325] | 2020 | 0 | – | 6.0 – 11.0 | – | – | ||
| EMA [326] | 2023 | 0.19 | 0.19 | – | – | 0.19 | ||
| Rituximab | CD20 | Terrier et al. [327] | 2010 | – | 9.0 | – | – | 1.4 |
| Maggi et al. [280] | 2011 | – | 10 – 77.0 | – | – | – | ||
| FDA (s.c.) [328] | 2021 | – | – | 13–26.0 | – | – | ||
| FDA (i.v.) [329] | 2021 | – | ≥ 25.0 | – | 2.0 – 8.0 | < 2.0 | ||
| BCCA [330] | 2024 | 1.0 – 10.0 | 14 – 77.0 | 20.0 | 7.0 | – | ||
| EMA [331] | 2024 | 1.0 – 10.0 | > 10.0 | < 20.0 | 1.0 – 10.0 | 0.01 – 0.1 | ||
| Riveiro-Barciela et al. [332] | 2024 | – | 9.0 | – | – | 2.8 | ||
| Secukinumab | IL-17A | Blauvelt [333] | 2016 | – | 0.7 | – | – | |
| Deodhar et al. [334] | 2019 | 2.4 | 0.8–1.3 | – | – | |||
| Grace et al. [335] | 2020 | – | 25.0 | – | – | |||
| Asawanonda et al. [336] | 2022 | – | 0.6 | – | – | |||
| Li et al. [337] | 2022 | – | 2.3 | – | – | |||
| FDA [338] | 2023 | 0.01 – 0.1 | – | 0.6 – 1.2 | – | |||
| EMA [339] | 2023 | – | – | 0.1 – 1.0 | 0.01 – 0.1 | |||
| Kim et al. [256] | 2023 | – | 1.9 | – | – | |||
| Tezepelumab | Anti-TSLP | Menzies-Gow et al. [340] | 2021 | – | 3.6 | – | 0 | |
| Corren et al. [341] | 2023 | – | 4.0 | – | 0 | |||
| EMA [342] | 2024 | – | 3.8 | – | – | |||
| Tralokinumab | IL-13 | Wollenberg et al. [343] | 2019 | – | 5.2 | – | – | |
| Panettieri et al. [344] | 2018 | – | 4.0–5.4 | – | 0 | |||
| Busse et al. [345] | 2019 | – | 15.7 | – | 0 | |||
| Carlsson et al. [346] | 2019 | 13.2 – 25.9 | – | < 1.0 | 0 | |||
| Silverberg et al. [347] | 2021 | 6.7 | ||||||
| FDA [348] | 2023 | – | 7.4 – 11.1 | – | – | |||
| EMA [349] | 2023 | – | 7.2 | – | – | |||
| Paller et al. [40] | 2023 | – | 2.1 – 9.2 | – | 0 | |||
| Upadacitinib | JAK inhibitor | FDA [350] | 2023 | 2.0 – 3.0 | – | 2.0 – 3.0 | 2.0 – 3.0 | |
| EMA [351] | 2023 | 0.1 – 1.0 | 1.0 – 10.0 | 0.1 – 1.0 | ||||
| Ustekinumab | IL-12 / IL-23 | Ghosh et al. [352] | 2019 | <1.0 | 0.1 | – | < 1.0 | 0 |
| FDA [353] | 2023 | 0.08 | – | 1.0 – 5.0 | – | 0.1 | ||
| EMA [354] | 2023 | 0.1 – 1.0 | 1.9 | 0.1 – 10.0 | 0.08 | 0.01 – 0.1 | ||
| Kim et al. [256] | 2023 | – | – | 2.8 | 0.1 – 1.0 | – |
aResults of clinical studies with asthma in FDA 2023 label. bResults of pooled chronic idiopathic urticaria trials in FDA 2023 label. JAK = Janus kinase; TSLP = thymic stromal lymphopoietin; HSR = hypersensitivity reaction; IR = infusion reaction, substance-specific; ISR = injection-site reaction.