Table 5.

Safety outcomes (adverse events of special interest) of RCTs investigating targeted synthetic DMARDs

Population	Study	Risk of bias	Treatment	n	Safety endpoint (week)	Serious adverse event	Serious infectious event	Opportunistic infection	Herpes zoster	Malignancy (other than NMSC)	Major adverse cardiovascular event	Venous thromboembolism
csDMARD-IR; bDMARD naive	McInnes 2021 (SELECT PsA 1)18	Low	UPA 15 mg OD ± csDMARD	429	24	14 (3.3)	5 (1.2)	1 (0.2)	4 (0.9)	1 (0.2)	0	0
			UPA 30 mg OD ± csDMARD	423		13 (3.1)	4 (0.9)	0	3 (0.7)	1 (0.2)	0	1 (0.2)
			ADA 40 mg Q2W ± csDMARD	429		16 (3.7)	3 (0.7)	0	0	3 (0.7)	2 (0.5)	2 (0.5)
			PBO ± csDMARD	423		26 (6.1)	11 (2.6)	2 (0.5)	5 (1.2)	0	1 (0.2)	1 (0.2)
bDMARD-IR	Mease 2021 (SELECT PsA 2)12	low	UPA 15 mg OD ± csDMARD	211	24	12 (5.7)	1 (0.5)	0	3 (1.4)	2 (0.9)	1 (0.5)	1 (0.5)
			UPA 30 mg OD ± csDMARD	218		18 (8.3)	6 (2.8)	2 (0.9)	8 (3.7)	2 (0.9)	0	0
			PBO ± csDMARD	212		4 (1.9)	1 (0.5)	0	2 (0.9)	0	0	0
Mixed (NSAID/csDMARD/bDMARD-IR)	Mease 2022 (DEUC Phase 2)11	low	DEUC 6 mg OD ± csDMARD	70	16	0	0	0	0	0	NR	0
			DEUC 12 mg OD ± csDMARD	67		0	0	0	0	0	NR	0
			PBO ± csDMARD	66		1 (1.5)	0	0	0	0	NR	1 (1.5)
Mixed (NSAID/csDMARD/bDMARD-IR)	Mease 2023 (BREP Phase 2)10	low	PBO ± csDMARD	67	16	1 (1.5)	0	0	0	0	0	0
			BREP 10 mg OD ± csDMARD	31		0	0	0	1 (3.2)	0	0	0
			BREP 30 mg OD ± csDMARD	60		3 (5.0)	2 (3.3)	0	1 (1.7)	0	0	0
			BREP 60 mg OD ± csDMARD	59		1 (1.7)	0	0	0	2 (3.3)	0	0

ADA, adalimumab; bDMARD, biological disease-modifying antirheumatic drug; BREP, brepocitinib; csDMARD, conventional synthetic DMARD; DEUC, deucravacitinib; IR, insufficient response; NMSC, non-melanoma skin cancer; NR, not reported; NSAID, non-steroidal anti-inflammatory drug; OD, once daily; RCT, randomised controlled trial; UPA, upadacitinib.