Using asthma medication off-label leads to disease remission in EGPA
Benralizumab, approved as Fasenra, found effective as add-on treatment
Using benralizumab — a medication approved in the U.S. for a rare type of asthma — off-label as an add-on to standard induction treatment resulted in a high rate of disease remission in people with eosinophilic granulomatosis with polyangiitis (EGPA) and severe asthma.
That’s according to a real-world study in Germany that also showed that adding benralizumab, the ingredient in AstraZeneca’s Fasenra, to standard maintenance treatment reduced respiratory exacerbations and the use of oral glucocorticoids.
While oral glucocorticoids are a mainstay EGPA treatment, their long-term use and high doses of them are associated with serious side effects.
These findings suggest that treatment with benralizumab, especially early on, may be effective as an add-on therapy in EGPA patients, the researchers noted.
“We hypothesize that early initiation of benralizumab in addition to [oral glucocorticoids] and other indicated immunosuppressive therapies might help to control the disease faster, to prevent further eosinophil-induced damage and facilitate down-tapering [glucocorticoids] thus preventing side effects,” the team wrote.
Their study, “Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis,” was published in the journal Dovepress.
Analyzing treatment outcomes in 26 adults with EGPA
EGPA is a rare type of ANCA-associated vasculitis (AAV), a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. This rare form is associated with high numbers of eosinophils, a type of immune cell, that build up in small blood vessels.
It results in symptoms that most commonly affect the respiratory tract. Many patients experience severe eosinophilic asthma, a rare form of asthma associated with high eosinophil counts. Benralizumab, as Fasenra, is used as an add-on maintenance therapy for that type of asthma.
The therapy targets the IL-5 receptor protein on eosinophils’ surface, leading to their death. It is known to reduce disease exacerbations, or periods of sudden symptom worsening, as well as glucocorticoid use, in people with eosinophilic asthma.
In EGPA clinical trials, benralizumab was found to be as effective as Nucala (mepolizumab) at inducing disease remission, and more effective at allowing glucocorticoid discontinuation. Nucala is an approved EGPA add-on treatment that works in a similar way as benralizumab.
Now, researchers from LMU University Hospital, in Munich, retrospectively analyzed the treatment outcomes of 26 adults with severe asthma and EGPA who were treated with benralizumab as part of either their induction treatment — aimed at inducing disease remission — or their maintenance treatment, designed to maintain remission.
All patients were followed at a single severe asthma center in Germany and had at least one year of data before starting benralizumab treatment. Benralizumab was administered at a dose of 30 mg via a single subcutaneous or under-the-skin injection, once a month for three months, and then every two months.
A total of nine patients had been diagnosed less than six months before they started benralizumab as an add-on to high-dose daily oral glucocorticoids. The remaining 17 patients had been diagnosed more than six months before beginning the use of benralizumab as an add-on to maintenance treatment with a stable dose of oral glucocorticoids.
Exacerbations were defined as worsening respiratory symptoms requiring stronger oral glucocorticoid therapy for at least three consecutive days. Clinical remission was defined as the absence of active disease manifestations while on a stable, low oral glucocorticoid dose.
Patients in the induction group — five men and four women — had a mean age of 55 at their EGPA diagnosis. At the start of benralizumab treatment, one-third also were on cyclophosphamide as pulse immunosuppressive therapy for life-threatening disease, and one patient had previously received Nucala.
Use of benralizumab linked to high rates of disease remission
All seven patients who continued treatment for one year achieved disease remission. They also experienced significantly fewer respiratory exacerbations per year (zero vs. two) and significantly reduced their daily doses of oral glucocorticoids (2.5 vs. 40 mg/day), with two patients discontinuing glucocorticoids.
The 12 women and five men in the maintenance group had a mean age of 49 at their EGPA diagnosis, and had been diagnosed with asthma about 20 years before. Benralizumab was started a median of six years after EGPA diagnosis.
The patients also were all receiving asthma-specific medications, and up to about one-quarter (24%) were on immunosuppressants, most commonly methotrexate. Nearly half (47%) had previously received off-label Nucala treatment, at a lower dose, before its approval for EGPA in the U.S.
The most common reason for adding benralizumab was glucocorticoids’ side effects (65%), followed by persistent respiratory symptoms and eosinophilia (53% each).
Nearly all patients (88%) continued benralizumab for at least one year, resulting in significantly fewer annual respiratory exacerbations (zero vs. one) and an increased proportion of patients with well-controlled asthma (88% vs. 25%).
Our long-term follow-up for a median of more than 4 years found that the majority of patients continued benralizumab treatment long-term, preserving good tolerability and outcome.
Daily glucocorticoid dose also was significantly decreased (2 vs. 8 mg/day), with nearly half of the patients (46%) discontinuing glucocorticoids.
“Our long-term follow-up for a median of more than 4 years found that the majority of patients continued benralizumab treatment long-term, preserving good tolerability and outcome,” the researchers wrote.
These findings highlighted that benralizumab “reduced respiratory exacerbations, enabled reduction of daily [glucocorticoid] doses in maintenance therapy phase, and was associated with high rates of remission when added during induction therapy phase,” the team wrote.
The limitations of this study, as pointed out by researchers, were its small number of patients and the fact that they were identified at a single asthma center, potentially affecting their characteristics.
Nonetheless, the team concluded that this “study should therefore serve as experience for clinicians, corroborating earlier studies as well as generating hypotheses for future controlled studies that need to address early EGPA as well as remission induction therapy of EGPA.”
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