Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis associated with asthma and blood and tissue eosinophilia. EGPA is often associated with glucocorticoid (GC)-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and anti-IL-5/anti-IL-5R are ineffective, other therapeutic options may be proposed. Tezepelumab, a monoclonal antibody that inhibits the binding of thymic stromal lymphopoietin (TSLP) to the TLSP receptor, approved for severe asthma, may be an option. We describe the safety and efficacy of off-label use of tezepelumab in relapsing and/or refractory EGPA.

Methods: We conducted a retrospective multicentre European study in EGPA patients who satisfied the 2022 ACR/EULAR classification criteria and received tezepelumab for relapsing or refractory EGPA. Relapsing disease was defined as active vasculitis (Birmingham Vasculitis Activity Score, BVAS >0) or active asthma symptoms or worsening sinonasal manifestations requiring an increase in oral GC dose. Refractory disease was defined as the inability to reduce GC below 7.5 mg/day due to active disease while tapering prednisone. Complete response was defined by BVAS=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day.

Results: Ten patients (median age 46 (38-52) years, 60% females) were included. All patients were previously treated with benralizumab, 6 (60%) with mepolizumab and 2 (20%) with dupilumab. The indications for tezepelumab were uncontrolled asthma in all cases (100%), disabling ENT manifestations in 7 (70%) and high-dose GC-dependency in 7 (70%). The median interval between stopping the previous biologic and starting tezepelumab was 2 (1-2.5) months.

Median follow-up after starting tezepelumab was 6 (3.2-8.7) months, including two patients with less than 3 months of follow-up (not evaluable for efficacy). Five out of 8 patients (62.5%) achieved a complete response and 1/8 (12.5%) a partial response. Median prednisone dose was 10 mg/day (0-40) at the start of tezepelumab and decreased to 0 mg/day (0-5) at 6 months. GC were completely stopped in 4 patients (50%). Median FEV1 at the start of tezepelumab was 57.5% (48-63.7) and increased to 75% (61-86) at 6 months. The median eosinophilia count was 0 (0-120) per mm3 at baseline and reached to 307 (225-397) at 6 months.

Two patients relapsed while on tezepelumab. One patient with initial improvement at 3 months experienced progressive worsening of dyspnea with marked sputum eosinophilia (56%) at 6 months, while blood eosinophilia increased from 0 to 300/mm3, leading to discontinuation of tezepelumab. One patient with arthralgia and arthritis was treated with rituximab. Two patients reported mild to moderate treatment-emergent arthralgia, one patient had epistaxis, and two patients had non-severe viral respiratory infections.

Conclusion: These results suggest that tezepelumab may be effective in the treatment of patients with EGPA and refractory or relapsing asthma and/or ENT manifestations and may allow GC sparing. The safety profile appeared to be favorable, with no risk of drug-associated eosinophilia.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tezepelumab-for-relapsing-or-refractory-eosinophilic-granulomatosis-with-polyangiitis-a-european-retrospective-study/