Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis

Figures & data

Figure 1 STROBE diagram of patient cohort.

Table 1 Reasons for Starting Benralizumab in Group A (Maintenance Therapy Phase)

Reasons for starting benralizumab	n=17
OCS side-effects (irrespective of dosage)	11 (65%)
Persisting asthma symptoms	9 (53%)
Persistent blood eosinophilia	9 (53%)
Recurrent exacerbations	6 (35%)
Failure to taper OCS below 7.5 mg/day	6 (35%)
Persisting symptoms of sinus disease	5 (29%)
Side-effects/intolerability of OCS-sparing immunosuppression	4 (24%)

Notes: Reasons for starting benralizumab in maintenance phase: multiple reasons were possible.

Abbreviation: OCS, oral glucocorticosteroid.

Table 2 Baseline Characteristics of Patients Starting Benralizumab in in Group A and B (Maintenance and Induction Therapy Phase)

Baseline characteristics	Group A Maintenance Therapy Phase (n=17)	Group B Induction Therapy Phase (n=9)
Age (years), mean (SD)	58 (18)	55 (14)
Age at asthma diagnosis (years), median (IQR)	29 (19–47)	NA
Age at EGPA diagnosis (years), median (IQR)	49 (30–66)	55 (37–61)
Female, n (%)	12 (71%)	4 (44%)
BMI (kg/m^2), median (IQR)	22 (21–24)	23 (22–25)
Time between EGPA diagnosis and start of benralizumab, median (IQR)	6 (2–9) (years)	0 (0–3) (months)
Sensitization to aeroallergens, n (%)	9 (53%)	5 (56%)
Polysensitization (≥3), n (%)	3 (18%)	1 (11%)
Former smokers, n (%)	3 (18%)	4 (44%)
Clinical manifestations
Asthma, n (%)	17 (100%)	9 (100%)
CRS, n (%)	16 (94%)	8 (89%)
Pulmonary infiltrates or other interstitial lung abnormalities, n (%)	14 (82%)	9 (100%)
Peripheral nervous system involvement, n (%)	6 (35%)	2 (22%)
Cardiac involvement, n (%)	7 (41%)	6 (67%)
Muco-/cutaneous involvement, n (%)	3 (18%)	0
Central nervous system involvement, n (%)	2 (12%)	0
Ocular involvement, n (%)	1 (6%)	0
Renal involvement, n (%)	0	1 (11%)
Laboratory findings
Blood eosinophil count at diagnosis (%), mean (SD)	29 (17)	39 (16)
Blood eosinophil count at diagnosis (G/L), mean (SD)	3.2 (2.4)	6.2 (3.0)
Blood eosinophil count at start of benralizumab (G/L), median (IQR)	0.15 (0.06–0.37)	0.33 (0.03–0.85)
NTproBNP at diagnosis (pg/mL), median (IQR)*	979 (358–1139)	5693 (1341–10,859)
NTproBNP at start of benralizumab (pg/mL), median (IQR)**	669 (234–1083)	405 (133–8157)
Presence of pANCA/MPO-ANCA antibodies, n (%)	2 (12%)	0 (0%)
Presence of cANCA antibodies, n (%)	0 (0%)	1 (11%)
Presence of PR3-ANCA antibodies, n (%)	0 (0%)	0 (0%)
Presence of atypical ANCA antibodies, n (%)	2 (12%)	2 (22%)
Previous discontinued therapy
Previous anti-IL5 therapy (mepolizumab), n (%)	8 (47%)	1 (11%)
Previous azathioprine, n (%)	6 (35%)	0
Previous cyclophosphamide, n (%)	4 (24%)	0
Previous MTX, n (%)	2 (12%)	0
Previous rituximab, n (%)	2 (12%)	0
Disease control
Asthma control test (ACT), median (IQR)***	19 (15–21)	20 (7–23)
Respiratory exacerbations in previous 12 months, median (IQR)	1 (0–2)	NA
Therapy at initiation of benralizumab
ICS/LABA, n (%)	17 (100%)	9 (100%)
LAMA, n (%)	10 (59%)	6 (67%)
LTRA, n (%)	1 (6%)	2 (22%)
OCS, n (%)	17 (100%)	9 (100%)
OCS dose in prednisolone equivalent (mg/day), median (IQR)	8 (4–15)	40 (20–60)
MTX, n (%)	4 (24%)	0
Azathioprine, n (%)	2 (12%)	0
Cyclosporine A, n (%)	1 (6%)	0
Cyclophosphamide, n (%)	0	3 (33%)

Notes: Baseline characteristics of EGPA patients in maintenance and induction phase. *NTproBNP at diagnosis was available for 3/7 patients with cardiac manifestation in maintenance phase and for 4/6 patients with cardiac manifestation in induction phase. **NTproBNP at initiation of benralizumab was available for 4/7 patients with cardiac manifestation in maintenance phase and for 6/6 patients with cardiac manifestation in induction phase. ***ACT at initiation of benralizumab was available in 9/17 patients in maintenance phase and in 6/9 patients in induction phase.

Abbreviations: BMI, body mass index; CRS, chronic rhinosinusitis; ENT, ear nose and throat; IL5, interleukin-5; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; MTX, methotrexate; ANCA, antineutrophil cytoplasmic antibodies; MPO, myeloperoxidase; CNS, central nervous system.

Table 3 Comparison of Outcome Parameters at Baseline (Start) and After 12 Months of Benralizumab Therapy in Group A (Maintenance Therapy Phase)

Outcome parameters (n=15°)	Baseline	12 Months	P-value
Clinical parameters, median (IQR)
OCS dose (prednisolone equivalent) (mg/d)	8 (4–15)	2 (0–5)	0.003*
Exacerbations in previous 12 months	1 (0–2)	0 (0–0)	0.007*
ACT, N=8	18 (14–22)	23 (21–25)	0.125*
Asthma control status (n)			0.029^#
- well controlled (ACT≥20)	2	7
- partially controlled (ACT 16–19)	4	0
- uncontrolled (ACT<16)	2	1
Pulmonary function testing, mean (SD)
FEV1 (L)	2.33 (0.73)	2.54 (0.84)	0.039^+
FEV1% predicted	75.0 (16.4)	82.0 (19.7)	0.043^+
FVC (L)	3.40 (0.69)	3.56 (0.80)	0.079^+
FVC% predicted	90.13 (8.67)	94.40 (11.47)	0.069^+
MEF25-75 (L/s)	1.54 (0.93)	1.89 (1.12)	0.013^+
MEF25-75% predicted	44.3 (24.9)	57.7 (29.8)	0.008^+
RV (L)	2.87 (0.83)	2.69 (0.86)	0.12^+
RV% predicted	140.9 (31.1)	130.9 (31.7)	0.07^+
Biomarkers, median (IQR)
BEC (G/l)	0.12 (0.05–0.34)	0 (0–0)	0.0001*
FeNO (ppb), N=11	57 (23–150)	41 (20–185)	0.31*

Notes: Comparison of outcome parameters at baseline (start) and after 12 months of benralizumab therapy in the maintenance cohort. °In this analysis we included only patients who continued benralizumab for 12 months and had outcome parameters available for both timepoints (n=15 unless stated otherwise). Statistics: *Paired Wilcoxon test; ⁺Paired t-test; ^#Chi-square test.

Abbreviations: Bold, significant parameters; OCS, oral glucocorticosteroid; ACT, asthma control test; BEC, blood eosinophil count; FeNO, exhaled fraction of NO.

Figure 2 Comparison of parameters of OCS use and symptoms (A), lung function (B), and biomarkers (C) before and after 12 months of benralizumab of patients in maintenance cohort. In this analysis we included all 15 patients who continued benralizumab for 12 months. Statistics: (A), (C): Wilcoxon matched-pairs signed-rank test; (B): paired t-test, *p<0.05, **p< 0.01, ***p<0.001.

Abbreviations: BEC, blood eosinophil count; FeNO, fraction of exhaled NO; OCS, oral glucocorticosteroid; ns not significant.

Table 4 Comparison of Outcome Parameters at Baseline (Start of Benralizumab) and After 12 Months of Benralizumab Therapy in Group B (Induction Therapy Phase)

Outcome parameters (n=7°)	Baseline	12 Months	P-value
Clinical parameters, median (IQR)
OCS dose (prednisolone equiv) (mg/d)	40 (30–70)	2.5 (0–5)	0.015*
Exacerbations in previous 12 months	2 (1–4)	0 (0–0)	0.031*
Pulmonary function testing, mean (SD)
FEV1 (L)	2.62 (1.08)	2.89 (1.01)	0.36^+
FEV1% predicted	84.6 (30.9)	91.4 (23.4)	0.50^+
FVC (L)	3.67 (1.43)	4.04 (1.13)	0.30^+
FVC% predicted	97.7 (34.5)	105.6 (14.9)	0.44^+
MEF25-75 (L/s)	1.93 (0.91)	2.18 (1.18)	0.43^+
MEF25-75% predicted	56.3 (24.5)	61.4 (28.7)	0.54^+
RV (L)	2.34 (0.72)	2.19 (1.06)	0.66^+
RV% predicted	117.0 (30.5)	104.0 (44.7)	0.46^+
Biomarkers, median (IQR)
BEC (G/l)	0.48 (0.07–3.95)	0 (0–0.165)	0.093*
FeNO (ppb), N=6	53 (27.25–196)	45 (26.75–83)	0.31*

Notes: Comparison of outcome parameters at baseline (start of benralizumab) and after 12 months of benralizumab therapy in the induction cohort. °In this analysis we included only patients who continued benralizumab for 12 months and had outcome parameters available for both timepoints (n=7 unless stated otherwise). Statistics: *Paired Wilcoxon test; ⁺Paired t-test.

Abbreviations: Bold, significant parameters, OCS, oral glucocorticosteroid; BEC, blood eosinophil count; FeNO, exhaled fraction of NO.

Figure 3 Comparison of parameters of OCS use and exacerbations (A), lung function (B), and biomarkers (C) before and after 12 months of benralizumab in induction cohort. In this analysis we included all 7 patients who continued benralizumab for 12 months. Statistics: Wilcoxon matched-pairs signed-rank test, *p<0.05.

Abbreviations: BEC, blood eosinophil count; FeNO, fraction of exhaled NO; ns not significant.

Table 5 Long-Term Follow-Up in Patients Who Continued Benralizumab Beyond 12-Month Timepoint

	Maintenance cohort (n=15)	Induction cohort (n=7)
Patients continuing benralizumab at October 1, 2023, n (%)	14 (93%)	6 (85%)
Duration of benralizumab per patient at October 1, 2023 in months, median	51	46
Total patient years of benralizumab treatment	57	27
Reasons for discontinuation of benralizumab
- Death due to metastatic breast cancer	1	0
- Increasing BEC at end of benralizumab interval	0	1
Any OCS increase during follow-up from 12-month timepoint to October 1, 2023, number of events	5	1
Changes/additions of systemic treatments for EGPA, asthma, CRSwNP	1
- Addition of dupilumab to benralizumab for uncontrolled CRSwNP
- Addition of rituximab to benralizumab for increasing reticulo-nodular lung abnormalities on HRCT	1
Infections requiring hospitalization
- Bacterial airway infection (Pseudomonas aer.)	2	0
- Viral airway infection (influenza A)	1	0
- Parasitic infection (Echinococcus)^Citation24	1	0

Barnikel M, Grabmaier U, Mertsch P, et al. Domestic parasitic infections in patients with asthma and eosinophilia in Germany - three cases with learnings in the era of anti- IL5 treatments. J Asthma Allergy. 2023;16:1229–1232. doi:10.2147/JAA.S428607

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