Table 2

Univariate and multivariate analysis of risk factors for severe or life-threatening infection following rituximab treatment during 24 months of follow-up

	Univariate analysis			Multivariate analysis
	HR	95 % CI	P values	HR	95 % CI	P values
Demographics
Age (years)	1.02	1.00 to 1.04	0.031	1.03	1.01 to 1.05	0.012
Gender (male)	0.88	0.50 to 1.55	0.647
Type of vasculitis
GPA	Reference	–	–
MPA	1.59	0.78 to 3.23	0.203
EGPA	0.95	0.42 to 2.15	0.899
Symptoms/manifestations
B-symptoms (night sweat, fever, unintentional weight loss)	0.67	0.28 to 1.58	0.355
Neuropathy	0.89	0.46 to 1.70	0.72
Sinusitis	0.48	0.27 to 0.84	0.01
Deafness/mastoiditis/otitis media	0.69	0.35 to 1.35	0.275
Arthralgia	0.63	0.35 to 1.14	0.127
Organ involvement
CNS	1.12	0.35 to 3.63	0.85
Subglottic/tracheal stenosis	1.14	0.51 to 2.54	0.746
Skin	0.74	0.33 to 1.64	0.45
Kidney	1.27	0.72 to 2.21	0.411
Eye	0.52	0.23 to 1.17	0.113
Others	0.82	0.26 to 2.65	0.745
ENT	0.46	0.26 to 0.82	0.008
Lung	1.57	0.87 to 2.82	0.136
Imaging findings
Pulmonary cavities	1.11	0.56 to 2.21	0.765
Endobronchial	2.44	1.38 to 4.32	0.002	2.21	1.14 to 4.26	0.018
Severe bronchiectasis	4.79	1.47 to 15.59	0.009
Disease activity measures
BVAS	1.01	0.95 to 1.07	0.811
DEI	0.98	0.84 to 1.15	0.840
Laboratory values
Creatinine	1	1.00 to 1.00	0.141
eGFR (MDRD equation) mL/min/1.73 m²	0.99	0.98 to 1.00	0.011
CRP	1.01	1.00 to 1.01	0.061
ESR	1.01	1.00 to 1.02	0.014
Neutrophils	1.11	1.03 to 1.20	0.005
WBC	1.06	1.01 to 1.10	0.013
Lymphocytes	0.73	0.48 to 1.11	0.142
CD19	1.17	0.11 to 12.51	0.896
CD3	0.75	0.45 to 1.25	0.27
CD4	0.74	0.34 to 1.61	0.44
CD8	0.58	0.16 to 2.09	0.407
CD56	2.75	0.34 to 22.10	0.341
IgG	1.02	0.93 to 1.12	0.663
IgG decline ≥30 %	1.88	1.04 to 3.39	0.036
Hypogammaglobulinaemia	1.22	0.54 to 2.74	0.633
IgM	0.72	0.38 to 1.35	0.304
IgA	1.11	0.80 to 1.54	0.535
ANCA positive	1.11	0.58 to 2.14	0.744
Comorbidities
COPD	16.07	4.41 to 58.49	<0.001	6.3	1.08 to 36.75	0.041
Diabetes	2.35	1.14 to 4.85	0.021
Hypertension	0.79	0.44 to 1.44	0.445
Myocardial infarction/reduced LVEF	2.21	1.07 to 4.56	0.032
Indication
Minor relapse	0.6	0.32 to 1.11	0.102
Major relapse	1.63	0.92 to 2.90	0.097
Maintenance	1.15	0.56 to 2.37	0.708
Refractory disease	0.8	0.42 to 1.51	0.491
Steroid sparing	1.37	0.70 to 2.68	0.36
1st line	1.95	0.77 to 4.91	0.159
Premedication (last 12 months)
CYC (g)	0.97	0.90 to 1.04	0.389
MMF (g)	1	1.00 to 1.00	0.273
AZA (g)	0.97	0.95 to 1.00	0.066
MTX (mg)	1	1.00 to 1.00	0.979
IVIG (ever)	2.4	0.94 to 6.12	0.067
Anti-TNF (ever)	1.41	0.34 to 5.84	0.636
PLEX (ever)	0.75	0.23 to 2.42	0.629
ALM (ever)	2.49	1.05 to 5.91	0.039	3.97	1.50 to 10.54	0.006
Medication used concurrently with RTX
Steroids (mg)	1.02	1.01 to 1.04	0.006
Trimethoprim–sulfamethoxazole	0.45	0.23 to 0.88	0.02	0.3	0.13 to 0.69	0.005
Other antibiotic prophylaxis	1.63	0.76 to 3.47	0.209

Demographics of the respective patients, the form of ANCA-associated vasculitis, symptoms, laboratory values, comorbidities, indication for rituximab use, the premedication and the concomitant therapy are given. P values indicating significant changes are highlighted in bold font.
ALM, alemtuzumab; ANCA, antineutrophil cytoplasm antibody; AZA, azathioprine; BVAS, Birmingham Vasculitis Activity Score; CD, cluster of differentiation; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CRP, C reactive protein; CYC, cyclophosphamide; DEI, Disease Extent Index; eGFR, estimated glomerular filtration rate; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear, nose and throat; ESR, erythrocyte sedimentation rate; GPA, granulomatosis with polyangiitis; IVIG, intravenous immunoglobulins; LVEF, left ventricular ejection fraction; MMF, mycophenolate mofetil; MPA, microscopic polyangiitis; MTX, methotrexate; PLEX, plasma exchange; RTX, rituximab; TNF, tumour necrosis factor; WBC, white blood count.