Table 5.

Reported allergic reactions to biotechnological substances (Rheumatology)

Biologics	ROA	Feature	Author	Year	HSR %	IR %	ISR %	Urticaria %	Anaphylaxis %
Adalimumab	s.c.	Human	Puxeddu et al. [116]	2012	3.5	–	1.5	1.5	0
			Tarkiainen et al. [117]	2015	18.1		17.0	–	–
			FDA [118]	2018	6.0		8.0–20.0	6.0**	–
Anakinra	s.c.	Human	EMA [119]	2014	–	–	≥10.0	0.1–1.0	0.1–1.0
			FDA [120]	2018	–		71.0*	–	–
Belimumab	s.c. i.v.	Human	EMA [124]	2018	< 10.0	7.0–12.0	6.1	–	0.1–1.0
			FDA [125]	2019	13.0	17.0	–	–	0.6
Canakinumab	s.c.	Human	FDA [126]	2016	–	–	≥10.0	–	0
Etanercept	s.c.	Humanized	Puxeddu et al. [116]	2012	5.3	–	1.6	2.0	0.8
			Tarkiainen et al. [117]	2015	11.3		7.5	–	–
			FDA [128]	2018	<2.0		15–37.0	2.0	<2.0
Golimumab	s.c.	Human	Kay et al. [129]	2015	–	–	4.7–11.6	–	0
			FDA [130]	2018	–		3.4–6.0	–	0
Infliximab	i.v.	Chimeric	Maggi et al. [65]	2011	–	1.0–27.0	–	–	–
			Puxeddu et al. [116]	2012	13.8	–	0	4.4	9.3
			Tarkiainen et al. [117]	2015	34.1	–	1.9	–	1.9
			FDA [131]	2019	–	18.0	–	<1.0	<1.0
Certolizumab	s.c.	Humanized	EMA [134]	2015	0.2–1.1	–	6.4	–	–
			FDA [135]	2019	–		1.7–3.2	0.3	–
Rituximab	i.v. s.c.	Chimeric	Maggi et al. [65]	2011	–	10–77.0	–	–	–
			FDA (s.c.) [137]	2017	–	–	16–26.0	–	–
			FDA (i.v.) [138]	2018	–	≥25.0	–	2.0–8.0	–
			BCCA [139]	2018	1–10.0	14–77.0	20.0	7.0	–

ROA route of administration, HSR hypersensitivity reaction, IR infusion reaction, ISR Injection-site reaction, s.c. subcutaneous, i.v. intravenous, FDA Food and Drug Administration, EMA European Medicines Agency, BCCA British Columbia Cancer Agency

*any grade of reactions

**immune-mediated rash