Fasenra linked to sustained remission in EGPA: Real-world data
Therapy also associated with a reduction in daily oral corticosteroid dose
Fasenra (benralizumab) provides meaningful benefits for people with eosinophilic granulomatosis with polyangiitis (EGPA), including those testing positive for self-reactive antibodies called ANCAs, according to a systematic review of real-world data.
Specifically, Fasenra was associated with sustained remission rates, significant corticosteroid-sparing effects, and reductions in symptoms related to the respiratory system or not.
“The evidence presented here complements the limited clinical trial data and demonstrates that [Fasenra] is effective in a broader, real-world population, including patients with [blood vessel inflammation] features and possibly those with prior [Nucala] treatment,” researchers wrote.
Nucala (mepolizumab) was the first approved therapy for EGPA, with Fasenra being the second.
The study, “Systematic Literature Review of Real-world Outcomes of Benralizumab in Eosinophilic Granulomatosis with Polyangiitis,” was published in The Journal of Allergy and Clinical Immunology: In Practice. The study was funded by Astrazeneca, the company that markets Fasenra.
EGPA treatment usually relies on corticosteroids
EGPA is a rare type of ANCA-associated vasculitis (AAV), a group of conditions marked by inflammation of small blood vessels that can result in organ damage.
People with this rare AAV type often have high blood levels of eosinophils, a type of immune cell, and eosinophilic asthma, or asthma associated with high eosinophils. Up to 80% also develop ear, throat, and nose (ETN) manifestations. ANCAs, the most common type of AAV-driving self-reactive antibody, are detected in up to 40% of EGPA patients.
EGPA treatment usually relies on corticosteroids, but their long-term use can have serious side effects.
Fasenra is an injectable therapy that blocks the signaling from IL-5, a molecule that recruits eosinophils to inflamed tissues. It was first approved for severe eosinophilic asthma, but it was later cleared for use as an add-on therapy for adults with EGPA in the U.S., and for those with relapsing or treatment-resistant EGPA in the European Union.
Fasenra’s approval was mainly based on data from the Phase 3 MANDARA clinical trial (NCT04157348), which showed that Fasenra was at least as effective as Nucala in maintaining remission in adults with relapsing or treatment-resistant EGPA. Fasenra was also superior to Nucala at allowing patients to stop oral corticosteroids.
ANCA status did not significantly impact remission rates
In this study, an international team of researchers set out to assess Fasenra’s safety and efficacy in a broader, real-world population. They did so by systematically reviewing studies published up to January 2024.
A total of 32 case reports covering 41 patients and seven patient group studies covering 306 patients were included in the analysis. Participants’ mean age ranged from 42 to 56 years. ANCAs were detected in 17.6% to 33.3% of group study patients and 48.8% of case report patients.
Nearly all people received Fasenra at the dosage used for eosinophilic asthma, since the therapy hadn’t yet been approved for EGPA at the time of these studies.
Most people received oral corticosteroids alongside Fasenra. Other immunosuppressive therapies were used by 40% to 66% of participants. Additionally, Nucala was previously used in 24% to 60% of group study patients and 12% of case report patients.
A total of 51 group study patients and five case report patients switched from Nucala to Fasenra, most commonly due to failure to achieve remission (64%). Reasons for switching were not available for case reports.
Remission was defined as no active disease, reflected by a zero on the Birmingham Vasculitis Activity Score (BVAS), and a low oral corticosteroid dose. It was only reported for group studies. Remission rates varied from 42% to 67% at one year and from 66% to 71% at two years.
ANCA status did not significantly impact remission rates, although slightly higher rates were seen in ANCA-positive patients. Disease remission was attained regardless of prior Nucala, but its use was linked with a tendency for lower remission rates (37% vs. 60%).
Disease duration did not significantly impact remission rates
Higher eosinophil counts upon starting Fasenra were associated with a higher likelihood of achieving remission in two studies. Corticosteroid-dependent symptoms, no prior anti-IL5 therapy, better lung function, and better asthma control were also linked with remission.
Other factors, such as disease duration and simultaneous use of immunosuppressants, did not significantly impact remission rates.
Fasenra treatment was also associated with a reduction in daily oral corticosteroid dose by 75% to 91% across all studies. Between 32% to 68% of group study patients and 51% of case report patients were able to discontinue these medications altogether.
Significant reductions in the BVAS, reflecting less disease activity, were reported in studies that used this parameter. Reductions in immunosuppressant use were also reported for between 26% and 100% of patients across studies.
The real-world reports identified … demonstrate that, in patients with EGPA, [Fasenra] is associated with significant [oral corticosteroid-sparing] effects and improvements in disease activity.
ANCA status changed from positive to negative in 50% to 67% of group study patients and 63% of case report patients. Complete eosinophil depletion was reported in five of six group studies within six to 12 months, with effects sustained at two years in two studies. Eosinophil counts also decreased significantly in case reports.
Fasenra was found to lessen not only ENT and lung manifestations, but also generalized symptoms like fatigue and weight loss, joint-related manifestations, and neurological involvement — features that had not been examined in the MANDARA trial.
The therapy was generally well tolerated, with adverse events mostly mild and rarely leading to treatment discontinuation.
“The real-world reports identified … demonstrate that, in patients with EGPA, [Fasenra] is associated with significant [oral corticosteroid-sparing] effects and improvements in disease activity,” the researchers wrote.
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