Safety and effectiveness of subcutaneous tocilizumab in patients with rheumatoid arthritis in a real-world clinical setting

Figures & data

Figure 1. Patient disposition in the 26-week postmarketing surveillance program. CDAI: Clinical Disease Activity Index; CRF: case report form; DAS28-ESR: Disease Activity Score in 28 joints as measured by erythrocyte sedimentation rate; IV: intravenous; RA: rheumatoid arthritis; TCZ: tocilizumab. ^aPatient data up to time of discontinuation were available for DAS28-ESR and CDAI calculations.

Table 1. Patient demographic and baseline characteristics.

	Total population, N = 1003	TCZ naïve, n = 784	TCZ-IV-SC, n = 219
Age, years
Mean (SD)	60.6 (14.0)	60.9 (14.0)	59.5 (14.2)
Median	63.0	63.0	61.0
Sex, n (%)
Male	146 (14.5)	120 (15.3)	26 (11.8)
Female	857 (85.4)	664 (84.6)	193 (88.1)
Disease duration (SD) [range], years	10.4 (9.7)	9.9 (9.9)	11.9 (8.7)
	[0.0, 62.9]	[0.0, 62.9]	[1.1, 50.5]
	(n = 839)	(n = 654)	(n = 185)
Body weight (SD) [range], kg	53.4 (9.1)	53.4 (9.2)	53.6 (9.0)
	[30.0, 91.4]	[30.0, 89.0]	[38.0, 91.4]
	(n = 972)	(n = 755)	(n = 217)
BMI (SD)	22.1 (3.3)	22.1 (3.2)	22.1 (3.4)
	(n = 786)	(n = 597)	(n = 189)
Steinbrocker disease stage classification, n (%)
Stage I	172 (17.1)	148 (18.8)	24 (10.9)
Stage II	327 (32.6)	263 (33.5)	64 (29.2)
Stage III	257 (25.6)	194 (24.7)	63 (28.7)
Stage IV	247 (24.6)	179 (22.8)	68 (31.0)
DAS28-ESR, mean (SD)	4.2 (1.7) (n = 742)	4.8 (1.3) (n = 568)	2.1 (1.2) (n = 174)
Duration of prior TCZ-IV administration at baseline, mean (SD) [range], days	–	–	884.7 (644.2)
	–	– (n = 0)	[50, 2999] (n = 219)
csDMARD, n (%)	712 (70.9)	568 (72.4)	144 (65.7)
Methotrexate	545 (54.3)	436 (55.6)	109 (49.7)
Corticosteroids, n (%)	445 (44.3)	368 (46.9)	77 (35.1)
Self-injection, n (%)^a	562 (56.0)	406 (51.7)	156 (71.2)
Concurrent disease, n (%)	594 (59.2)	447 (57.0)	147 (67.1)
Respiratory disease	114 (11.3)	84 (10.7)	30 (13.6)
Diabetes mellitus	70 (6.9)	54 (6.8)	16 (7.3)

BMI: body mass index; csDMARD: conventional synthetic biologic disease-modifying antirheumatic drug; DAS28-ESR: Disease Activity Score in 28 joints as measured by erythrocyte sedimentation rate; TCZ: tocilizumab; TCZ-IV-SC: patients who switched from intravenous to subcutaneous tocilizumab.

^a Includes any patient that self-injected at least once.

Table 2. Adverse events and serious adverse events.

	Total population, N = 1003		TCZ naïve, n = 784		TCZ-IV-SC, n = 219
%	AEs	SAEs	AEs	SAEs	AEs	SAEs
Overall	28.2	4.9	29.5	5.2	23.2	4.1
Infections and infestations	7.4	1.7	8.2	2.2	4.5	0.0
Laboratory investigations^a	5.9	0.2	6.8	0.2	2.7	0.4
Metabolism and nutrition disorders	4.0	0.0	4.7	0.1	1.8	0.0
Skin and subcutaneous tissue disorders	3.1	0.1	3.0	0.2	3.6	0.0
Musculoskeletal and connective tissue disorders	2.8	0.1	2.5	0.1	4.1	0.4
Gastrointestinal disorders	2.6	0.2	3.1	0.3	0.9	0.0
General disorders and administration site conditions	2.6	0.1	2.1	0.2	4.5^b	0.0
Respiratory, thoracic, and mediastinal disorders	2.3	0.3	1.7	0.2	4.5^b	0.9
Hepatobiliary disorders	1.6	0.0	1.9	0.1	0.9	0.0
Nervous system disorders	0.6	0.4	0.5	0.2	1.3	1.3
Injury, poisoning, and procedural complications	0.5	0.2	0.6	0.2	0.4	0.4
Neoplasms^c	0.4	0.4	0.5	0.5	0.4	0.4
Blood and lymphatic system disorders	0.4	0.0	0.3	0.1	0.9	0.0
Cardiac disorders	0.2	0.2	0.3	0.3	0.0	0.0
Vascular disorders	0.2	0.0	0.3	0.1	0.0	0.0
Endocrine disorders	0.1	0.0	0.1	0.1	0.4	0.0
Eye disorders	0.1	0.0	0.2	0.0	0.0	0.0
Renal and urinary disorders	0.1	0.0	0.2	0.1	0.0	0.0
Psychiatric disorders	0.0	0.0	0.0	0.0	0.4	0.0
Ear and labyrinth disorders	0.0	0.0	0.1	0.0	0.0	0.0
Reproductive system and breast disorders	0.0	0.0	0.0	0.0	0.4	0.4

AEs: adverse events; SAEs: serious adverse events; TCZ: tocilizumab; TCZ-IV-SC: patients who switched from intravenous to subcutaneous tocilizumab.

^a This refers to the system organ class “Investigations” from the Medical Dictionary for Regulatory Activities.

^b These events occurred in a few patients each.

^c Includes benign, malignant, and unspecified neoplasms, as well as cysts and polyps.

Table 3. Adverse events per 100 patient years.

	Total population, N = 1003		TCZ naïve, n = 784		TCZ-IV-SC, n = 219
Per 100 PY	AE	SAE	AE	SAE	AE	SAE
Overall	94.4	13.9	98.9	15.0	78.8	10.1
Infections and infestations	19.3	4.5	21.7	5.8	11.1	0.0
Laboratory investigations^a	16.2	0.6	18.8	0.5	7.0	1.0
Metabolism and nutrition disorders	9.2	0.2	10.7	0.2	4.0	0.0
Skin and subcutaneous tissue disorders	8.5	0.4	8.4	0.5	9.1	0.0
General disorders and administration site conditions	7.6	0.4	6.3	0.5	12.1^b	0.0
Gastrointestinal disorders	7.2	0.9	8.7	1.1	2.0	0.0
Musculoskeletal and connective tissue disorders	7.2	0.4	6.3	0.2	10.1	1.0
Respiratory, thoracic, and mediastinal disorders	5.8	0.9	4.3	0.5	11.1^b	2.0
Hepatobiliary disorders	3.8	0.2	4.3	0.2	2.0	0.0
Nervous system disorders	1.8	1.1	1.4	0.5	3.0	3.0
Injury, poisoning, and procedural complications	1.3	0.6	1.4	0.5	1.0	1.0
Neoplasms^c	1.3	1.3	1.4	1.4	1.0	1.0
Blood and lymphatic system disorders	1.1	0.2	0.8	0.2	2.0	0.0
Cardiac disorders	0.9	0.9	1.1	1.1	0.0	0.0
Vascular disorders	0.6	0.2	0.8	0.2	0.0	0.0
Endocrine disorders	0.4	0.2	0.2	0.2	1.0	0.0
Eye disorders	0.4	0.0	0.5	0.0	0.0	0.0
Renal and urinary disorders	0.4	0.2	0.5	0.2	0.0	0.0
Ear and labyrinth disorders	0.2	0.0	0.2	0.0	0.0	0.0
Psychiatric disorders	0.2	0.0	0.0	0.0	1.0	0.0
Reproductive system and breast disorders	0.2	0.2	0.0	0.0	1.0	1.0

AE: adverse events; PY: patient year; SAE: serious adverse events; TCZ: tocilizumab; TCZ-IV-SC: patients who switched from intravenous to subcutaneous tocilizumab.

^a This refers to the system organ class “Investigations” from the Medical Dictionary for Regulatory Activities.

^b These events occurred in a few patients each.

^c Includes benign, malignant, and unspecified neoplasms, as well as cysts and polyps.

Figure 2. CDAI, DAS28-ESR, and remission by group over 26 weeks. Median (IQR) CDAI (a) and mean (SD) DAS28-ESR (b) from baseline to week 26 for patients in the TCZ-naïve and TCZ-IV-SC groups. CDAI (c) and DAS28-ESR (d) remission rates from baseline to week 26 in the TCZ-naïve and TCZ-IV-SC groups. CDAI: Clinical Disease Activity Index; DAS28-ESR: Disease Activity Score in 28 joints as measured by erythrocyte sedimentation rate; IQR: interquartile range; SD: standard deviation; TCZ: tocilizumab; TCZ-IV-SC: patients who switched from intravenous to subcutaneous tocilizumab.