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Observational Study
. 2023 Jun 30:14:1204444.
doi: 10.3389/fimmu.2023.1204444. eCollection 2023.

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study

Santi Nolasco  1   2 , Andrea Portacci  3 , Raffaele Campisi  2 , Enrico Buonamico  3 , Corrado Pelaia  4 , Alida Benfante  5 , Massimo Triggiani  6 , Giuseppe Spadaro  7 , Maria Filomena Caiaffa  8 , Giulia Scioscia  9 , Aikaterini Detoraki  10 , Giuseppe Valenti  11 , Francesco Papia  11 , Alessandra Tomasello  5 , Nunzio Crimi  1 , Nicola Scichilone  5 , Girolamo Pelaia  4 , Giovanna Elisiana Carpagnano  3 , Claudia Crimi  1   2
Affiliations
Observational Study

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study

Santi Nolasco et al. Front Immunol. .

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia.

Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months.

Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed.

Results: 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients.

Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.

Keywords: Churg-Strauss; EGPA; IL-5; benralizumab; eosinophilic granulomatosis with polyangiitis; mepolizumab; oral corticosteroid; remission.

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Conflict of interest statement

AP has received speaker fees from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. AB has received speaker fees from AstraZeneca, GlaxoSmithKline, and Sanofi. MT has received speaker and consultancy fees from Novartis, AstraZeneca and GlaxoSmithKline. GSc has received speaker fees from AstraZeneca, GlaxoSmithKline, and Sanofi. AD has received speaker fees from Sanofi, AstraZeneca, GlaxoSmithKline, Novartis, Lofarma. GV has received speaker fees from GlaxoSmithKline, and Sanofi. NC has received speaker and lecturer fees from AstraZeneca, GlaxoSmithKline and Sanofi. NS has received speaker fees from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. GP has received speaker and lecturer fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Guidotti, Menarini, Novartis and Sanofi. GC has received grants from AstraZeneca, GlaxoSmithKline, Chiesi, Sanofi and Grifols; has received speaker and lecturer fees from AstraZeneca, GlaxoSmithKline, and Sanofi; has received supports for attending meetings from AstraZeneca, Menarini and Chiesi. CC has received speaker fees from ResMed, Fisher&Paykel, Sanofi, AstraZeneca, GlaxoSmithKline and Menarini. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor EH declared a past co-authorship with the authors SN, RC, CP, AB, MT, GS, MC, AD, NC, NS, GP, GC and CC.

Figures

Figure 1
Figure 1
The effect of anti-IL-5/Rα biologicals on BVAS score is presented with box and whisker plots (A). Boxes display median and interquartile ranges, whiskers define maximum and minimum values. (B) Percentage of patients in remission according to MIRRA criteria. (C) Kaplan-Meier curve for the occurrence of relapses. BVAS, Birmingham vasculitis activity score. *p<0.05.
Figure 2
Figure 2
Effects of anti-IL-5/Rα biologicals on annual asthma exacerbation rate (A), occurrence of asthma exacerbations (B), ACT score (C) and FEV1% (D). The annual asthma exacerbation rate, the ACT score and the FEV1% are expressed as median values (interquartile range). The occurrence of asthma exacerbations is presented with a Kaplan-Meier curve. ACT, asthma control test; FEV1, forced expiratory volume in the 1st second. *p<0.05.
Figure 3
Figure 3
Changes in FEV1 (L) (A), FVC% (B), FEV1/FVC% (C) and FEF25-75% (D). Data are expressed as median values (interquartile range). FEV1, forced expiratory volume in the 1st second; FVC, forced vital capacity; FEF25-75, forced expiratory flow between 25% and 75% of FVC. *p<0.05.
Figure 4
Figure 4
Changes in blood eosinophil (A) and basophil (B) count. Data are expressed as median values (interquartile range). *p<0.0001.
Figure 5
Figure 5
OCS daily dose reduction (A) and withdrawal (B). The OCS daily dose is presented as median values (interquartile range). OCS, oral corticosteroids (prednisone equivalent dose). *p<0.05.
See this image and copyright information in PMC

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