Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who were refractory or intolerant to anti-tumor necrosis factor therapy: Subgroup analysis of a randomized, double-blind, multicenter, phase 3 study (SIRROUND-T)

Figures & data

Figure 1. Study design and patient disposition for Japanese subgroup. EE: easy escape; CO: crossover.

Table 1. Demographic and baseline characteristics.

		Sirukumab
	Placebo n = 37	50 mg q4w n = 35	100 mg q2w n = 44	Total N = 116
Age, years	54.1 (11.7)	57.0 (13.2)	57.8 (8.1)	56.4 (11.0)
Female	28 (75.7)	30 (85.7)	32 (72.7)	90 (77.6)
Weight, kg	56.8 (11.8)	58.4 (12.2)	55.5 (10.5)	56.8 (11.4)
BMI, kg/m^2	22.6 (4.2)	24.0 (4.2)	22.3 (4.1)	22.9 (4.2)
Disease duration, year	9.5 (6.8)	12.0 (9.7)	10.8 (7.4)	10.8 (8.0)
Rheumatoid factor-positive	27 (73.0)	31 (88.6)	27 (61.4)	85 (73.3)
Anti-CCP antibody positive	31 (83.8)	34 (97.1)	38 (86.4)	103 (88.8)
Swollen joint count (0–66)	12.2 (8.0)	10.7 (5.7)	10.8 (7.4)	11.2 (7.1)
Tender joint count (0–68)	16.2 (9.7)	17.6 (11.6)	17.3 (11.9)	17.0 (11.1)
HAQ-DI score (0–3)	1.3 (0.6)	1.3 (0.8)	1.3 (0.6)	1.3 (0.7)
CRP (mg/L)	37.4 (32.2)	29.3 (30.1)	28.0 (28.1)	31.4 (30.1)
DAS28 (CRP)	5.6 (1.0)	5.4 (1.2)	5.4 (1.0)	5.4 (1.1)
Clinical disease activity index score (0–76)	31.9 (10.8)	31.2 (12.0)	30.6 (12.4)	31.2 (11.7)
Simplified disease activity index score (0–86)	35.6 (11.9)	34.2 (14.1)	33.4 (12.9)	34.3 (12.9)
Previous treatment
Biological DMARDs
Anti-TNF agent
1	24 (64.9)	26 (74.3)	30 (68.2)	80 (69.0)
≥2	13 (35.1)	9 (25.7)	14 (31.8)	36 (31.0)
Concomitant medications at baseline
DMARDs	34 (91.9)	30 (85.7)	39 (88.6)	103 (88.8)
MTX	26 (70.3)	25 (71.4)	33 (75.0)	84 (72.4)
MTX dose at baseline
0	11 (29.7)	9 (25.7)	11 (25.0)	31 (26.7)
>0 to <12.5 mg/week	21 (56.8)	22 (62.9)	21 (47.7)	64 (55.2)
≥12.5 mg/week	5 (13.5)	3 (8.6)	12 (27.3)	20 (17.2)
Oral corticosteroids	24 (64.9)	19 (54.3)	36 (81.8)	79 (68.1)
NSAIDs	34 (91.9)	31 (88.6)	39 (88.6)	104 (89.7)

All data are given in mean (SD) or n (%). BMI: body mass index; CCP: cyclic citrullinated peptide; CRP: C-reactive protein; DMARDs: disease-modifying anti-rheumatic drugs; DAS28: disease activity score for 28 joints; HAQ-DI: health assessment questionnaire disability index; MTX: methotrexate; NSAIDs: nonsteroidal anti-inflammatory drugs; SD: standard deviation; TNF: tumor necrosis factor.

Figure 2. Proportion of patients who achieved an ACR 20 and ACR 50 response over time (Efficacy full analysis set). ^aThe confidence intervals are based on the Wald statistic; ^bThe p values are based on the CMH test. ACR: American college of rheumatology; CI: confidence interval.

Table 2. Summary of secondary efficacy endpoints through week 24 (full analysis set).

	Placebo (n = 37)	50 mg sirukumab every 4 weeks (n = 35)			100 mg sirukumab every 2 weeks (n = 44)
	Outcome at week 24	Outcome at week 24	Differences (95% CI)	p Value^a	Outcome at week 24	Differences (95% CI)	p Value^a
ACR endpoints
ACR 20	8 (21.6)	20 (57.1)	0.358 (0.158, 0.558)	.001	21 (47.7)	0.246 (0.048, 0.445)	.025
ACR 70	0	4 (11.4)	0.116 (0.013, 0.220)	.034	6 (13.6)	0.140 (0.034, 0.246)	.020
DAS28 (CRP) endpoints
DAS28 (CRP) remission	2 (5.4)	13 (37.1)	0.326 (0.155, 0.497)	<.001	17 (38.6)	0.331 (0.169, 0.492)	<.001
Change from baseline	−0.27 (1.20)	−2.24 (1.46)	−2.070 (−2.643, −1.497)	<.001	−2.52 (1.16)	−2.31 (−2.862, −1.765)	<.001
DAS28 (CRP) response	9 (24.3)	25 (71.4)	0.476 (0.282, 0.670)	<.001	27 (61.4)	0.361 (0.162, 0.560)	.002
SDAI (change from baseline)	−1.5 (13.24)	−18.3 (14.48)	−16.819 (−22.997, −10.641)	<.001	−19.2 (11.93)	−17.318 (−23.235, −11.402)	<.001
CDAI (change from baseline)	−1.4 (12.43)	−15.8 (13.62)	−14.466 (−20.303, −8.629)	<.001	−16.5 (11.55)	−14.707 (−20.297, −9.117)	<.001
ACR/EULAR remission endpoints
SDAI-based ACR/EULAR remission	1 (2.7)	2 (5.7)	0.033 (0.060, 0.126)	.487	6 (13.6)	0.119 (0.002, 0.235)	.063
Boolean-based ACR/EULAR remission	1 (2.7)	1 (2.9)	0.002 (−0.066, 0.069)	.967	5 (11.4)	0.092 (−0.016, 0.201)	.121
HAQ-DI endpoints
Change from baseline in HAQ-DI Score	−0.01 (0.40)	−0.40 (0.61)	−0.389 (−0.617, −0.161)	.001	−0.34 (0.50)	−0.351 (−0.570, −0.133)	.002
HAQ-DI response	11 (29.7)	17 (48.6)	0.192 (−0.027, 0.412)	.101	24 (54.5)	0.240 (0.030, 0.449)	.034
Proportion achieving HAQ-DI ≤0·5	8 (21.6)	14 (40.0)	0.190 (−0.018, 0.397)	.086	15 (34.1)	0.110 (−0.085, 0.304)	.287

All data are in mean (SD) or n (%). ACR: American college of rheumatology; CDAI: Clinical Disease Activity Index; CRP: C-reactive protein; DAS28: disease activity score for 28 joints; EULAR: European League Against Rheumatism; HAQ-DI: health assessment questionnaire disability index; SD: standard deviation; SDAI: Simplified Disease Activity Index.

^aCompared to placebo.

Table 3. Summary of treatment-emergent adverse events (safety analysis set).

	Prior to week 24					Prior to week 52
	Placebo n = 37	Placebo→ Sirukumab 50 mg q4w n = 7	Placebo→ Sirukumab 100 mg q2w n = 9	Sirukumab 50 mg q4w n = 35	Sirukumab 100 mg q2w n = 44	Sirukumab 50 mg q4w Combined n = 49	Sirukumab 100 mg q2w Combined n = 59
Average duration of follow-up (weeks)	20.7 (3.84)	6.0 (0.85)	6.1 (0.45)	23.3 (2.30)	23.4 (1.89)	42.04	42.89
≥1 TEAEs	28 (75.7)	2 (28.6)	5 (55.6)	29 (82.9)	38 (86.4)	44 (89.8)	52 (88.1)
TEAEs leading to discontinuation of study drug	3 (8.1)	0	0	2 (5.7)	4 (9.1)	5 (10.2)	8 (13.6)
≥1 serious TEAEs	2 (5.4)	0	1 (11.1)	2 (5.7)	4 (9.1)	6 (12.2)	8 (13.6)
Deaths	0	0	0	0	0	0	0
Adverse events of special interest
≥1 serious infection	0	0	0	2 (5.7)	1 (2.3)	2 (4.1)	3 (5.1)
≥1 injection-site reaction	1 (2.7)	1 (14.3)	1 (11.1)	3 (8.6)	12 (27.3)	7 (14.3)	19 (32.2)
≥1 malignancy	0	0	0	0	1 (2.3)	0	1 (1.7)
≥1 gastrointestinal perforation	0	0	0	0	1 (2.3)	0	1 (1.7)
≥1 MACE	1 (2.7)	0	0	0	0	1 (2.0)	0
TEAEs in ≥5% of patients
Nasopharyngitis	7 (18.9)	0	0	4 (11.4)	9 (20.5)	13 (26.5)	16 (27.1)
Injection-site erythema	0	0	0	4 (11.4)	10 (22.7)	7 (14.3)	16 (27.1)
Alanine aminotransferase increased	2 (5.4)	0	1 (11.1)	3 (8.6)	4 (9.1)	10 (20.4)	7 (11.9)
Stomatitis	1 (2.7)	0	0	2 (5.7)	4 (9.1)	5 (10.2)	11 (18.6)
Injection-site pruritus	1 (2.7)	0	0	2 (5.7)	6 (13.6)	3 (6.1)	11 (18.6)
Aspartate aminotransferase increased	2 (5.4)	0	1 (11.1)	3 (8.6)	4 (9.1)	8 (16.3)	6 (10.2)
Injection-site swelling	0	1 (14.3)	1 (11.1)	0	4 (9.1)	2 (4.1)	9 (15.3)
Diarrhea	2 (5.4)	0	0	1 (2.9)	2 (4.5)	2 (4.1)	5 (8.5)
Upper respiratory tract infection	0	0	1 (11.1)	2 (5.7)	2 (4.5)	4 (8.2)	4 (6.8)
Leukopenia	0	0	0	1 (2.9)	2 (4.5)	3 (6.1)	4 (6.8)
Upper respiratory tract inflammation	0	0	1 (11.1)	2 (5.7)	2 (4.5)	3 (6.1)	3 (5.1)
Neutropenia	0	0	0	2 (5.7)	1 (2.3)	3 (6.1)	3 (5.1)

All values are presented as n (%) unless stated. The list of TEAEs is provided for ≥5% patients in sirukumab combined groups. CO: crossover; E: easy escape; MACE: major adverse cardiovascular events; TEAE: treatment-emergent adverse events.