Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label

Table 4 Meta-analysis of adverse events in randomized controlled trials of biological agents in patients with systemic autoimmune diseases

	Disease	Patients (n)		Total side effects (n)		Total infections (n)		Severe infections (n)
		Placebo	Biologic	Placebo	Biologic	Placebo	Biologic	Placebo	Biologic
Meijer et al [3]	Sjögren síndrome	10	20	4	16	4	11	NS	NS
Dass et al [4]	Sjögren síndrome	9	8	0	4	0	1	0	1
Merrill et al [5]	SLE	88	169	73	139	15	16	15	16
Stone et al [6]	ANCA-vasculitis	98	99	33	31	NS	NS	7	7
Jones et al [7]	ANCA-vasculitis	11	33	NS	NS	7	19	3	7
*RITUXIMAB*		216	329	110/205	190/296	26/118	47/230	25/206	31/309
				HR 1.55 (1.06-2.26)*		HR 0.97 (0.80-1.17)		HR 0.81 (0.45-1.48)
Hoffman et al [8]	Giant cell arteritis	16	28	15	26	9	20	1	3
Salvarani et al [9]	Rheumatic polym.	28	23	5	7	0	1	0	1
Baughman et al [10]	Sarcoidosis	44	89	41	80	32	54	4	10
Mariette et al [11]	Sjögren síndrome	49	54	1	6	0	1	0	1
*INFLIXIMAB*		137	194	62 (45.2%	119 (61.3%)	41	76	5	15
				HR 1.92 (1.20-3.06)*		HR 1.51 (0.92-2.47)		HR 2.21 (0.74-7.96)
Melikoglu et al [12]	Behcet	20	20	0	2	0	0	0	0
Baughman et al [13]	Sarcoidosis	9	9	5	2	2	2	0	0
Sankar et al [14]	Sjögren syndrome	14	14	1	2	1	0	0	0
WGET [15]	ANCA-vasculitis	91	89	51	51	45	44	NS	NS
Mtnez-Taboada et al [16]	Giant cell arteritis	9	8	7	8	4	4	0	0
*ETANERCEPT*		143	140	64 (44.7%)	65 (46.4%)	52 (36.4%)	50 (35.7%)	0 (0%)	0 (0%)
				HR 1.07 (0.65-1.75)		HR 0.97 (0.58-1.63)		Not calculable
TOTAL		496	663	236/485 (48.7%)	374/630 (59.4%)	119/398 (29.9%)	173/564 (30.7%)	30/395 (7.6%)	46/554 (8.3%)
				HR 1.54 (1.20-1.97)*		HR 1.04 (0.78-1.39)		HR 1.10 (0.67-1.84)

*P < 0.05; ANCA, anti-neutrophil antibodies; HR, hazard ratio; NS, not specified; SLE, systemic lupus erythematosus.

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