Remission of eosinophilic granulomatosis with polyangiitis possible with benralizumab

Key takeaways:

• After 1 year, 38 out of 56 patients no longer needed oral corticosteroids.
• The proportion of patients experiencing symptoms of acute vasculitis fell from 77.1% to 12.9% after 1 year of benralizumab.

Patients with eosinophilic granulomatosis with polyangiitis and severe eosinophilic asthma showed significant improvements in asthma control and acute vasculitis symptoms after 1 year of benralizumab, according to real-world study results.

“Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation,” Alexandra M. Nanzer, PhD, consultant respiratory physician at Guy’s and St. Thomas’ NHS Trust in London, and colleagues wrote. “Benralizumab, an anti-IL-5 receptor monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown.”

The retrospective cohort study included 70 patients (mean age, 49.4 years; 48.6% male) with EGPA and severe eosinophilic asthma who received at least 1 year of treatment with benralizumab (Fasenra, AstraZeneca) between May 2018 and May 2022 at Guy’s Hospital.

Researchers defined EGPA by a history of asthma, eosinophilia (> 10% or > 1,500 cells/µL) and at least two other symptoms, such as:

• eosinophilic vasculitis or eosinophilic granulomatous inflammation biopsy evidence;
• mononeuritis multiplex and/or motor neuropathy;
• pulmonary infiltrates or alveolar hemorrhage;
• sinonasal involvement;
• cardiomyopathy;
• glomerulonephritis;
• skin lesions compatible with vasculitis; and
• antineutrophilic cytoplasmic antibody (ANCA) positivity.

Clinical remission served as the study’s primary outcome, which researchers defined by an absence of active vasculitis, evaluated by the Birmingham Vasculitis Activity Score (BVAS), and oral corticosteroid dose of 4 mg per day or less of prednisolone 1 or 2 years after starting benralizumab treatment. Researchers identified patients as “super-responders” if they achieved remission and had no asthma or extrapulmonary relapses during the first 12 months of treatment.

About one-third of patients had used anti-IL-5 biologic therapy before switching to benralizumab, and 31% received additional immunosuppressive treatment.

Fifty-six (80%) patients were taking prednisolone at the beginning of benralizumab treatment with a mean dose of 13 ± 10.5 mg per day at baseline.

Seventy patients completed at least 1 year of treatment with benralizumab and 53 completed 2 years of treatment.

After 1 year of treatment, the mean dose of prednisolone dropped to 2.4 ± 6 mg per day (P < .0001). Further, of the 56 patients taking baseline prednisolone, 46 reduced their oral corticosteroid dose by 50% or more, and 38 patients did not need any oral corticosteroids after 1 year. Out of 41 patients who completed 2 years of treatment, 28 no longer needed oral corticosteroids.

Researchers also saw a significant decrease in active vasculitis. At baseline, 54 patients (77.1%) had a BVAS score above 0, compared with nine (12.9%) after 1 year of benralizumab treatment (P < .0001). After 2 years, four out of 53 (7.5%) had a BVAS score above 0 (P < .0001). Combining BVAS scores and oral corticosteroid reductions, 67.1% of patients achieved remission after 1 year of treatment and 67.9% achieved remission after 2 years.

After 1 year, 67.1% of patients had not experienced an asthma-related or extrapulmonary relapse, but after 2 years, that rate fell to 43.4%, with a nonsignificant trend observed of such relapses occurring less frequently among ACNA-negative patients. Nonasthma-related relapses appeared uncommon; after 1 year, 61 out of 70 patients were relapse free, and 45 out of 53 were relapse free after 2 years.

Nearly half (45.7%) of patients met super responder criteria after 1 year of benralizumab treatment, but after 2 years, the proportion fell to 34%. Researchers noted that rates were higher in the ANCA-negative subgroup at both time points, but they were not statistically significant.

“We have observed extremely positive clinical outcomes with benralizumab in EGPA including the ability to achieve corticosteroid-free clinical remission in the majority of patients,” the researchers wrote. “Given the more favorable safety profile of benralizumab compared with oral corticosteroids and other broad-spectrum immunosuppressive therapies, we believe that the appropriate treatment approach in EGPA is to directly target the eosinophil with anti-IL-5/5R therapy as a first-line option.”