Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study

Figures & data

Figure 1. Flow-chart of the study.

AHA: autoimmune hemolytic anemia; APS: antiphospholipid syndrome; SLE: systemic lupus erythematosus; MCTD: mixed connective-tissue disease; TPO-RA: thrombopoietin-receptor agonist; ITP: immune thrombocytopenia.

Table I. Characteristics of the included safety population with immune thrombocytopenia (ITP) receiving rituximab biosimilars.

General characteristics	Rixathon™	Truxima™	ITP-ritux
	n = 55	n = 52	n = 248
Female sex, n (%)	28 (73.7)	24 (75.0)	159 (64.1)
Age at first biosimilar infusion, median (IQR)	47.5 (33.3, 67.1)	55.0 (32.1, 70.0)	51.5 (34.3, 69.4)
ITP phase, n (%)
Newly diagnosed	10 (18.2)	4 (7.7)	45 (18.1)
Persistent	10 (18.2)	11 (21.2)	59 (23.8)
Chronic	35 (63.6)	37 (71.2)	144 (58.1)
Time between ITP diagnosis and first rituximab infusion, months, median (IQR)	30.2 (4.0, 104.8)	26.8 (9.9, 58.6)	16.2 (4.5, 69.7)
Previous use of MabThera™, n (%)	13 (23.6)	7 (13.5)	0
Characteristics at ITP diagnosis
Age (years), median (IQR)	41.8 (24.5, 57.4)	51.8 (25.8, 66.1)	45.0 (27.8, 63.8)
Platelet count (x109/l), median (IQR)	12.0 (6.0, 30.0)	16.0 (8.0, 39.0)	18 (6, 4)
Transient response to corticosteroids ITP, n (%)	45 (81.8)	42 (80.8)	182 (74.0)
ITP history before rituximab infusion
Previous use of IVIg, n (%)	34 (61.8)	34 (65.4)	175 (71.1)
Previous use of TPO-RA, n (%)	15 (27.3)	15 (28.8)	30 (12.2)
Previous use of immunosuppressive drug, n (%)	5 (9,1)	2 (3,8)	15 (6,0)
Previous splenectomy, n (%)	2 (3.6)	4 (7.7)	25 (10.2)
ITP treatment lines received before biosimilar infusion, median (IQR)*	1.0 (0.0, 1.7)	1.0 (0.0, 1.2)	0.0 (0.0, 1.0)
Bleeding score >8, n (%)	11 (20.0)	0	52 (21.1)
Characteristics at first rituximab infusion
Lowest platelet count (x10^9/l) in the month before infusion, median (IQR)	16.0 (7.5, 24.5)	19.50 (12.0, 34.0)	17.0 (7.0, 25.0)
Anti-CD20 schedule administration: fixed 1-g dose on day 1 and day 15, n (%)	53 (96.4)	48 (92.3)	72 (29.0)
Concomitant ITP treatment, n (%)
Corticosteroids	32 (58.2)	20 (36.4)	128 (51.6)
IVIg	7 (12.7)	4 (7.7)	20 (8.1)
TPO-RA	9 (16.4)	9 (17.3)	18 (7.3)
Dapsone	1 (1.8)	0
Hydroxychloroquine	1 (1.8)	4 (7.7)
Vinblastine	1 (1.8)	2 (6.2)	0
None	13 (23.6)	21 (40.4)	23 (9.3)
Steroids daily dose (mg/d), if applicable, (prednisone equivalent), median (IQR)	60.0 (0.0, 70.0)	40.0 (12.5, 57.5)	20.0 (1.0, 60.0)

The characteristics of the ITP-ritux control population are given for comparison.

*corticosteroids and intravenous immunoglobulin treatment not included. IQR, interquartile range; IVIg, intravenous immunoglobulin; TPO-RA, thrombopoietin-receptor agonist

Figure 2. Initial response after biosimilar treatment among the different populations. .

ITP: immune thrombocytopenia

Table II. Characteristics and outcomes for the Rixathon™ and matched control populations.

Baseline characteristics	Rixathon™	ITP-ritux matched controls	Standardized differences
	n = 34	n = 68
Female sex*, n (%)	24 (70.6)	48 (70.6)	0
Age at first biosimilar infusion*, median (IQR)	51.6 (38.3, 67.6)	52.6 (37.9, 68.7)	0.025
ITP phase*, n (%)			0.04
Newly diagnosed	7 (20.6)	13 (19.1)
Persistent	10 (29.4)	21 (30.9)
Chronic	17 (50.0)	34 (50.0)
Protocol 1-g dose on day 1 and day 15, n (%)	33 (97.1)	19 (27.9)	2
Corticosteroid-sensitive ITP*, n (%)	29 (85.3)	58 (85.3)	0
Previous use of TPO-RAs, n (%)	10 (29.4)	6 (9.0)	0.54
History of splenectomy*, n (%)	0	0	0
Treatment lines received before biosimilar infusion**, median (IQR)	1.0 (0.0, 1.0)	0.0 (0.0, 0.0)	0.9
Severe bleeding, n (%)	6 (17.6)	13 (19,1)	0.36
Efficacy outcomes			p-value
Response at month 3, n (%):			.01
Failure	8 (23.5)	33 (48.5)
Partial response	14 (41.2)	20 (29.4)
Complete response	12 (35.3)	15 (22.1)
Response at month 12***, n (%):			.04
Failure	10 (35.7)	33 (57.9)
Partial response	8 (28.6)	7 (12.3)
Complete response	10 (35.7)	17 (29.8)
Safety outcomes			p-value
Adverse effect during the first infusion, n (%)	3 (8.8)	4 (5.8)	.27
Post-rituximab infection	3 (8.8)	10 (14.7)	.4
Post-rituximab neutropenia	0	1 (1.5)	.9

* Matching variables; ** Apart from IVIg and corticosteroids; *** Available for only 28 patients in the biosimilar group and 57 in the reference product group. ITP, immune thrombocytopenia; IQR, interquartile range; IVIg, intravenous immunoglobulin; TPO-RA, thrombopoietin-receptor agonist

Table III. Characteristics and outcomes for the Truxima™ and matched control populations.

Baseline characteristics	Truxima™	ITP-ritux matched controls	Standardized differences
	n = 40	n = 80
Female sex*, n (%)	27 (67.5)	54 (67.5)	0
Age at first biosimilar infusion*, median (IQR)	53.5 (31.2, 70.0)	54.7 (29.9, 70.0)	0.01
ITP phase*, n (%)			0.27
Newly diagnosed	3 (7.5)	12 (15.0)
Persistent	11 (27.5)	16 (20.0)
Chronic	26 (65.0)	52 (65.0)
Protocol 1-g dose on day 1 and day 15, n (%)	40 (100)	23 (28,7)	1.86
Corticosteroid-sensitive ITP*, n (%)	38 (95.0)	76 (95.0)	0
Previous use of TPO-RA, n (%)	11 (27.5)	6 (7.5)	0.55
History of splenectomy*, n (%)	0	0	0
Treatment lines received before biosimilar infusion**, median (IQR)	1.0 (0.00 1.0)	0.0 (0.0, 0.0)	0.91
Severe bleeding, n (%)	0 (0.0)	11 (14.1)	0.43
Efficacy outcomes			p-value
Response at month 3, n (%):			.81
Failure	19 (47.5)	33 (44.6)
Partial response	6 (15.0)	18 (24.3)
Complete response	15 (37.5)	23 (31.1)
Response at month 12***, n (%):			.45
Failure	17 (53.1)	41 (60.3)
Partial response	5 (15.6)	4 (5.9)
Complete response	10 (31.2)	23 (33.8)
Safety outcomes			p-value
Adverse effect during the first infusion, n (%)	4 (10)	10 (12,5)	.65
Post-rituximab infection	3 (7.7)	22 (27.5)	.019
Post-rituximab neutropenia	1 (2.5)	0 (0.0)	.9

* Matching variables; ** Apart from IgIV and corticosteroids; *** Available for only 32 patients in the biosimilar group and 68 in the reference product group. ITP, immune thrombocytopenia; IQR, interquartile range; IVIg, intravenous immunoglobulin; TPO-RA, thrombopoietin-receptor agonist