Interleukin 6 and Rheumatoid Arthritis

Table 1

Randomized phase III controlled trials of tocilizumab.

(a) Clinical efficacy of tocilizumab (Tocilizumab combination therapy)

Study	Population	Week at evaluation	Treatment arms	Patient number	HAQ (% ≥MCID)	Response rates (%), OR (95% CI)			DAS28 < 2.6 remission rate (%), OR (95% CI)
						ACR20	ACR50	ACR70
TOWARD	DMARDs-IR	24 W	TCZ (8 mg/kg) + DMARDs	803	60****	61****	38****	21****	30****, 13.8
			DMARDs	413	34	25	9	3	3
RADIATE	Anti-TNF-IR	24 W	TCZ (4 mg/kg) + MTX	161	Δ−0.3^∗∗	30***	17****	5	8, 4.3
			TCZ (8 mg/kg) + MTX	170	Δ−0.4^∗∗∗∗	50***	29****	12****	30***, 21
			MTX	158	Δ−0.1	10	4	1	2
OPTION	MTX-IR	24 W	TCZ (4 mg/kg) + MTX	214	Δ−0.52^∗	48****, 2.6 (1.7–3.9)	31****, 3.8 (2.3–6.5)	12****, 7.0 (2.4–20.4)	13***, 18.8 (2.5–142)
			TCZ (8 mg/kg) + MTX	205	Δ−0.55^∗∗	59****, 4.0 (2.6–6.1)	44****, 6.6 (3.9–11.2)	22****, 14.2 (5.0–40.4)	27****, 45 (6.1–332)
			MTX	204	Δ−0.34	26	11	2	1
LITHE	MTX-IR	52 W	TCZ (4 mg/kg) + MTX	399	60	47*	29*	16*	30*, 4.92
			TCZ (8 mg/kg) + MTX	398	63*	56****	36****	20****	47****, 10.2
			MTX	393	53	25	10	4	8

(b) Tocilizumab monotherapy

Study	Population	Week at evaluation	Treatment arms	Patient number	HAQ (% ≥MCID)	Response rates (%), OR (95% CI)			DAS28 < 2.6 remission rate (%), OR (95% CI)
						ACR20	ACR50	ACR70
AMBITION	MTX, anti-TNF naïve	24 W	TCZ (8 mg/kg)	286	Δ−0.7	70***	44**	28***	34^n.d., 5.83 (3.27–10.4)
			MTX	284	Δ−0.5	53	34	15	12
SAMURAI	DMARDs-IR	52 W	TCZ (8 mg/kg)	157	68***	78***	64***	44***	59***, 46.5
			DMARDs	145	40	34	13	6	3
SATORI	MTX-IR	24 W	TCZ (8 mg/kg)	61	67****	80***	49^n.d.	30^n.d.	43***, 37.0
			MTX	64	34	25	11	6	2

^∗𝑃<0.05, ^∗∗𝑃<0.01, ^∗∗∗𝑃<0.001, ^∗∗∗∗𝑃<0.0001.
HAQ: health assessment questionnaire disability index; MCID: minimal clinical important difference; OR: odds ratio; CI: confidence interval; DMARDs: disease-modifying antirheumatic drugs; IR: inadequate response; TCZ: tocilizumab; TNF: tumor necrosis factor; MTX: methotrexate; n.d.: not described.

(c) Efficacy of tocilizumab in protection of radiographic progression of joints

Study	Radiographic assessment	Week at evaluation	Treatment arms	Proportion without progression TSS ≦ 0	Change in score (95% CI)
					Total score	Erosion score	JSN score
SAMURAI	van der Heijde-modified Sharp score	52 W	TCZ (8 mg/kg)	56**	2.3**, (1.5–3.2)	0.9***, (0.3–1.4)	1.5*, (0.9–2.1)
			DMARDs	39	6.1 (4.2–8.0)	3.2 (2.1–4.3)	2.9 (2.0–3.8)
LITHE	Genant-modified Sharp score	52 W	TCZ (4 mg/kg) + MTX	81****	0.34****	0.21*	0.13*
			TCZ (8 mg/kg) + MTX	84****	0.29****	0.17****	0.12**
			MTX	67	1.13	0.71	0.42

^∗𝑃<0.05, ^∗∗𝑃<0.01, ^∗∗∗𝑃<0.001, ^∗∗∗∗𝑃<0.0001.
TSS: total Sharp score; CI: confidence interval; TCZ: tocilizumab; DMARDs: disease-modifying antirheumatic drugs; JSN: joint space narrowing; MTX: methotrexate.