Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD

Article Figures & Data

Download figure
Open in new tab
Download powerpoint
Figure 1.
Incidence of neutropenia according to TCZ dose. (A) Comparison of neutropenia incidence between doses of 6 mg/kg versus 8 mg/kg. (B) Kinetic of ANC after a dose reduction. *** p < 0.001. TCZ: tocilizumab; ANC: absolute neutrophil count.
Download figure
Open in new tab
Download powerpoint
Figure 2.
Median drug survival by a Kaplan-Meier analysis between TCZ patients with and without neutropenia. TCZ: tocilizumab.

Table 1.

General characteristics of cohort.

Characteristics	Values
Patients, n	499
Age, yrs, mean (SD)	57.2 (29.3)
Male/female, %	17.1/82.9
Diagnosis, n (%)
Rheumatoid arthritis	361 (72.3)
Axial spondyloarthritis	101 (20.2)
Psoriatic arthritis	30 (6)
JIA	7 (1.4)
Antibody status, %
RA with RF- or ACPA-positive	63.7
ANA in cohort	6.3
Disease duration, yrs, mean (SD)	15.8 (11.2)
Prior no. biologics, IV or SC, mean (95% CI)	1.8 (1.6–2.3)
Concomitant therapy, overall/RA patients, n (%)
Methotrexate	218 (43.7)/193 (53.4)
Other sDMARD	39 (7.8)/30 (8.8)
Corticosteroids	246 (49.4)/179 (49.5)

JIA: juvenile idiopathic arthritis; RA: rheumatoid arthritis; RF: rheumatoid factor; ACPA: anticitrullinated protein antibody; ANA: antinuclear antibody; IV: intravenous; SC: subcutaneous; sDMARD: synthetic disease-modifying antirheumatic drug.

Table 2.

Characteristics of patients according to IV bDMARD. Values are % unless otherwise specified.

Characteristics	Abatacept	Infliximab	Tocilizumab	p^*
Patients, n (%)	129 (22.9)	213 (37.9)	221 (39.2)
Total time taking drug, mos, mean (SD)	27.4 (21.3)	41.7 (33.3)	31.1 (22.3)	0.03
Diagnosis
Rheumatoid arthritis	98.4	31.9	92.3
Axial spondyloarthritis	—	51.7	—
Psoriatic arthritis	—	13.6	—
JIA	1.6	2.8	7.2
Concomitant sDMARD^**
Methotrexate	59.6	44.6	66.8	< 0.001
Leflunomide	12.4	2.34	5.4	< 0.001
Corticosteroids	48.9	49.9	50.6	0.46

↵* p values are supplemented as appropriate.
↵** At baseline. IV: intravenous; DMARD: disease-modifying antirheumatic drugs; bDMARD: biological DMARD; JIA: juvenile idiopathic arthritis; sDMARD: synthetic DMARD.

Table 3.

Neutropenia and related variables according to IV bDMARD analyzed. Values are n unless otherwise specified.

Variables	Abatacept	Infliximab	Tocilizumab	p^*
Neutropenia, n (%)^**	5 (3.8)	6 (2.8)	41 (18.6)	< 0.001
Grade 1	1	0	4
Grade 2	4	3	33
Grade 3		2	4
Grade 4
Time to first episode of neutropenia, weeks, mean (range)	9.3 (3–11.5)	13.2 (2.2–18)	15.2 (1–108)	0.65
History of neutropenia, n (%)	4 (75)	3 (50)	3 (7.3)	< 0.001
sDMARD	3 (MTX)	2 (MTX)	1 (MTX)
Biologic drug		1 (ADA)	2 (1 ADA/1 ETN)
Hematologic disorder	1 (Felty)
Other cytopenias, n (%)	1 (20)	1 (16.6)	9 (21.9)	0.96
Thrombocytopenia		1	3 (2 with lymphopenia)
Lymphopenia			6
Pancytopenia	1

↵* p values are supplemented as appropriate.
↵** This value refers to the lowest ANC registered. IV: intravenous; DMARD: disease-modifying antirheumatic drugs; bDMARD: biological DMARD; sDMARD: synthetic DMARD; MTX: methotrexate; ADA: adalimumab; ETN: etanercept; ANC: absolute neutrophil count.

Table 4.

Predisposing factors of neutropenia. Values are % unless otherwise specified.

Variables	Univariate Analysis		p	Multivariate Analysis
Variables	Neutropenia, n = 52	Without Neutropenia, n = 447	p	OR	95% CI
Age, yrs, mean (SD)	60.3 (24.2)	56.5 (30.4)	0.27
Female	75	83.8	0.11
Rheumatoid arthritis	98	69.3	0.001	2.14	0.89–6.79
Disease duration, yrs, mean (SD)	16.3 (10.5)	15.4 (12.5)	0.61
RF- or ACPA-positive	65.3	63.5	0.96
Prior neutropenia receiving sDMARD therapy	11.5	1.7	0.015	1.56	1.17–7.14
Current treatment
Concomitant MTX	57.7	42.1	0.03	1.21	1.01–2.64
Concomitant PRED	48.1	49.4	0.88
0–5 mg/day	47.3	46.2	0.92
5–15 mg/day	32.4	36.1	0.75
> 15 mg/day	9.6	11.2	0.81
Abatacept	9.6	27.7	0.004
Infliximab	11.5	46.3	0.001
Tocilizumab	78.8	40.2	0.001	2.72	1.53–9.05

RF: rheumatoid factor; ACPA: anticitrullinated protein antibody; sDMARD: synthetic disease-modifying antirheumatic drug; MTX: methotrexate; PRED: prednisone.