Integrated safety in tocilizumab clinical trials

Table 6 Changes in ALT/AST values from normal at baseline to highest value in the all-control and in the all-exposed population

	Controlled, double-blind study population					All-exposed population
	Tocilizumab 8 mg/kg monotherapy, % (n) n= 288	Methotrexate (control), % (n) n= 284	Tocilizumab 4 mg/kg + DMARDs, % (n) n= 774	Tocilizumab 8 mg/kg + DMARDs, % (n) n= 1,582	DMARD monotherapy, % (n) n= 1,170	Tocilizumab, % (n/n) n= 4,009^c
ALT,^a n = normal at baseline	n = 269	n = 269	n = 706	n = 1,465	n = 1,080
> 1-3× ULN > 3-5× ULN > 5× ULN	33.8 (91) 1.1 (3) 0.7 (2)	32.0 (86) 2.6 (7) 1.1 (3)	42.8 (302) 4.0 (28) 1.0 (7)	45.9 (672) 4.3 (63) 1.4 (20)	19.1 (206) 0.8 (9) 0.3 (3)	57.3 (2,112/3,696) 7.2 (267/3,696) 2.2 (83/3,696)
AST,^a n = normal at baseline	n = 283	n = 269	n = 743	n = 1,502	n = 1,123
> 1-3× ULN > 3-5× ULN > 5× ULN	20.8 (59) 0.4 (1) 0.7 (2)	24.9 (67) 1.1 (3) 0.4 (1)	32.4 (241) 0.9 (7) --	38.8 (583) 1.5 (23) 0.2 (3)	14.5 (163) 0.3 (3) 0.1 (1)	51.4 (1,961/3,818) 2.6 (98/3,818) 0.6 (22/3,818)
Dose held^b	8.0 (23)	9.9 (28)	2.5 (19)	2.5 (39)	0.7 (8)	10.3 (413/4,009)
Discontinued	0.3 (1)^b	1.4 (4)^b	1.3 (10)^b	1.3 (21)^b	0.2 (2)^b	2.3 (91/4,002)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; DMARD, disease-modifying antirheumatic drug; ULN, upper limit of normal. ^aPercentages are based on number of patients with normal ALT (or AST) at baseline. ^bPercentages are based on total treatment-group sample size. ^cExcluding patients with missing values.

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