Long-term safety and efficacy of weekly subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis who had an inadequate response to subcutaneous tocilizumab every other week: Results from the open-label extension of the SHINOBI study

Figures & data

Figure 1. Patient disposition. AE: adverse event; TCZ-SC: subcutaneous tocilizumab; qw: weekly; q2w: every other week. ^a One patient was excluded due to having no evaluable measurements after study drug administration.

Table 1. Summary of adverse events (AEs) and serious adverse events (SAEs)^a from baseline to week 52 by body system.

	TCZ-SC total (N = 42)
	AE		SAE
	No. of events	n (%)^b	No. of events	n (%)^b
All body systems	143	38 (90.5)	12	8 (19.0)
Infections and infestations	36	23 (54.8)	3	2 (4.8)
Skin and subcutaneous tissue disorders	15	14 (33.3)	0	0
Gastrointestinal disorders	14	10 (23.8)	0	0
Investigations^c	20	9 (21.4)	0	0
Injury, poisoning and procedural complications	10	7 (16.7)	0	0
Respiratory, thoracic and mediastinal disorders	7	6 (14.3)	0	0
Musculoskeletal and connective tissue disorders	6	6 (14.3)	0	0
Blood and lymphatic system disorders	5	5 (11.9)	1	1 (2.4)
General disorders and administration site conditions	5	5 (11.9)	0	0
Neoplasms benign, malignant and unspecified	5	5 (11.9)	3	3 (7.1)
Psychiatric disorders	4	4 (9.5)	0	0
Hepatobiliary disorders	4	3 (7.1)	2	1 (2.4)
Nervous system disorder	3	3 (7.1)	1	1 (2.4)
Vascular disorders	3	3 (7.1)	1	1 (2.4)
Eye disorders	2	2 (4.8)	0	0
Metabolism and nutrition disorders	2	2 (4.8)	0	0
Cardiac disorders	1	1 (2.4)	1	1 (2.4)
Ear and labyrinth disorders	1	1 (2.4)	0	0

^a System organ class was used to categorize AEs and SAEs.

^b Patients with ≥1 AE, n (%).

^c Most common investigations were increases in blood cholesterol, triglycerides, and eosinophil count and decreases in white blood cell count.

Figure 2. Mean change in DAS28-ESR and CDAI from baseline to week 52. (a) Mean change in DAS28-ESR from baseline to week 52. (b) Mean change in CDAI from baseline to week 52. CDAI: Clinical Disease Activity Index; DAS28-ESR: Disease Activity Score based on 28 joints using erythrocyte sedimentation rate; TCZ-SC: subcutaneous tocilizumab; qw: weekly; q2w: every other week. Error bars represent the standard deviation.

Figure 3. DAS28-ESR and CDAI response at weeks 12 and 52. (a) DAS28-ESR^a response at weeks 12 and 52. (b) CDAI^b response at weeks 12 and 52. CDAI: Clinical Disease Activity Index; DAS28-ESR: Disease Activity Score based on 28 joints using erythrocyte sedimentation rate; HDA: high disease activity; LDA: low disease activity; MDA: moderate disease activity; TCZ-SC: subcutaneous tocilizumab; qw: weekly; q2w: every other week. ^a Remission was defined as DAS28-ESR <2.6; LDA as DAS28-ESR ≥2.6 to ≤3.2; MDA as DAS28-ESR >3.2 to ≤5.1; and HDA as DAS28-ESR >5.1. ^bRemission was defined as CDAI ≤2.8; LDA as CDAI >2.8 to ≤10; MDA as CDAI >10 to ≤22; and HDA as CDAI >22.

Table 2. Mean change in DAS28-ESR from baseline to week 12 by subgroup.

	TCZ-SC 162 mg qw (n = 21)			TCZ-SC 162 mg q2w (n = 20)
	n	Mean ΔDAS28-ESR (SD)	95% CI	n	Mean ΔDAS28-ESR (SD)	95% CI
Sex
Male	5	−2.29 (1.954)	−4.72 to 0.14	6	−0.33 (0.766)	−1.14 to 0.47
Female	16	−2.10 (1.690)	−3.00 to −1.19	14	−1.06 (1.223)	−1.77 to −0.36
Age, years
< 65	16	−2.04 (1.801)	−3.00 to −1.08	16	−1.04 (1.143)	−1.65 to −0.43
≥ 65	5	−2.47 (1.491)	−4.32 to −0.62	4	−0.05 (0.777)	−1.28 to 1.19
Body weight, kg
40 to <50	4	−2.11 (0.805)	−3.39 to −0.83	1	−2.97	−
50 to <60	4	−1.55 (2.672)	−5.80 to 2.70	7	−0.91 (1.162)	−1.98 to 0.17
60 to <70	8	−2.04 (1.401)	−3.21 to −0.87	7	−0.91 (0.783)	−1.64 to −0.19
≥ 70	5	−2.80 (2.091)	−5.40 to −0.20	5	−0.23 (1.263)	−1.80 to 1.34
BMI, kg/m^2
< 18.5	1	−2.87	−	0	−	−
18.5 to <25	11	−1.39 (1.744)	−2.57 to −0.22	9	−1.03 (1.281)	−2.02 to −0.05
≥ 25	9	−2.97 (1.367)	−4.02 to −1.92	11	−0.69 (1.044)	−1.39 to 0.01
RA disease duration, years
< 5	7	−2.07 (1.760)	−3.70 to −0.44	9	−0.93 (1.324)	−1.95 to 0.09
5 to <10	6	−2.88 (1.516)	−4.47 to −1.29	6	−0.46 (0.522)	−1.01 to 0.09
≥ 10	8	−1.65 (1.810)	−3.16 to −0.14	5	−1.15 (1.395)	−2.89 to 0.58
Steinbrocker class
I	1	−1.56	−	2	−0.78 (0.047)	−1.20 to −0.36
II	12	−1.81 (1.920)	−3.03 to −0.59	17	−0.85 (1.240)	−1.49 to −0.21
III	8	−2.71 (1.389)	−3.87 to −1.55	1	−0.87	−
Steinbrocker stage
I	5	−1.71 (2.144)	−4.37 to 0.95	5	−0.76 (1.301)	−2.38 to 0.85
II	5	−3.85 (0.957)	−5.04 to −2.66	6	−1.02 (1.193)	−2.27 to 0.23
III	7	−1.16 (1.498)	−2.55 to 0.22	8	−0.79 (1.222)	−1.81 to 0.24
IV	4	−2.26 (0.388)	−2.88 to −1.64	1	−0.67	−
DAS28-ESR at baseline
≤ 5.1	6	−1.33 (2.008)	−3.43 to 0.78	8	−0.90 (0.918)	−1.67 to −0.14
> 5.1	15	−2.47 (1.524)	−3.31 to −1.62	12	−0.80 (1.302)	−1.63 to 0.02
CRP, mg/dL
< 1	11	−1.82 (1.780)	−3.02 to −0.62	10	−1.08 (1.243)	−1.97 to −0.19
≥ 1	10	−2.50 (1.639)	−3.67 to −1.32	10	−0.61 (1.031)	−1.34 to 0.13
Previous bDMARDs for RA
Yes	13	−1.85 (1.558)	−2.79 to −0.91	17	−0.84 (1.058)	−1.39 to −0.30
No	8	−2.62 (1.935)	−4.23 to −1.00	3	−0.84 (1.830)	−5.39 to 3.70
Duration of TCZ-SC administration, weeks
< 24	17	−2.39 (1.729)	−3.28 to −1.51	12	−0.88 (1.380)	−1.76 to 0.00
≥ 24	4	−1.07 (1.252)	−3.06 to 0.93	8	−0.79 (0.720)	−1.39 to −0.19
RF
Positive	17	−2.33 (1.636)	−3.17 to −1.49	16	−0.77 (1.185)	−1.40 to −0.14
Negative	4	−1.33 (2.019)	−4.55 to 1.88	4	−1.16 (1.009)	−2.76 to 0.45
Anti-CCP antibody
Positive	18	−2.20 (1.688)	−3.04 to −1.36	17	−0.75 (1.149)	−1.34 to −0.16
Negative	3	−1.81 (2.174)	−7.22 to 3.59	3	−1.36 (1.128)	−4.16 to 1.44
Corticosteroid
Yes	12	−2.22 (1.347)	−3.08 to −1.37	10	−0.64 (1.224)	−1.52 to 0.24
No	9	−2.03 (2.183)	−3.71 to −0.36	10	−1.05 (1.069)	−1.81 to −0.28
TCZ concentration at week 12, µg/mL
< 1	1	−1.27	−	6	−0.50 (0.396)	−0.91 to −0.08
1 to ≤10	5	−2.82 (1.300)	−4.43 to −1.21	10	−1.41 (1.056)	−2.16 to −0.65
≥ 10	13	−2.20 (1.630)	−3.18 to −1.21	1	−2.13	−

bDMARDs: biologic disease-modifying antirheumatic drugs; BMI: body mass index; CCP: cyclic citrullinated peptide; CRP: C-reactive protein; DAS28-ESR: Disease Activity Score based on 28 joints using erythrocyte sedimentation rate; RA: rheumatoid arthritis; RF: rheumatoid factor; TCZ-SC: subcutaneous tocilizumab; qw: weekly; q2w: every other week. Last observation carried forward was used.

Data sharing statements

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