Nucala lowers disease activity, steroid use with EGPA in real world
Analysis of 30 adults being treated at rheumatology centers across Spain
Long-term treatment with Nucala (mepolizumab) reduces disease activity and helps to prevent progressive organ damage in people with eosinophilic granulomatosis with polyangiitis (EGPA), the rarest type of ANCA-associated vasculitis (AAV), data from a real-world study show.
Finding among patients in Spain also showed that most using Nucala were able to lower their dose of standard anti-inflammatory glucocorticoids, with about half discontinuing glucocorticoids altogether. This is relevant as long-term reliance on these therapies is linked to severe side effects.
“Our data suggests that [Nucala] is an effective and safe drug that allows glucocorticoids withdrawal without relapses,” the researchers wrote.
The study, “Mepolizumab efficacy and safety in patients with eosinophilic granulomatosis with polyangiitis in real practice: Data from a Spanish retrospective multicentric register from Rheumatology departments,” was published in the journal Reumatología Clínica.
Nucala approved as an add-on therapy to standard care for EGPA
EGPA is the rarest type of AAV, a group of autoimmune disorders marked by inflammation in and damage to small blood vessels. In this disease form, an excessive accumulation of eosinophils, a type of immune cell, in the blood and tissues leads to granulomas, or damaging clusters of immune cells.
The condition mainly affects the lungs and gastrointestinal system, with many patients experiencing asthma-like symptoms before receiving a diagnosis.
Nucala, developed by GlaxoSmithKline, is approved as an add-on to standard care with glucocorticoids for certain EGPA patients in multiple regions, including the U.S. and European Union.
It works by targeting interleukin-5 (IL-5), a key regulator of eosinophil development, survival, and movement within the body, to lower eosinophil levels.
Nucala’s approvals were supported by findings from the Phase 3 MIRRA clinical trial (NCT02020889), which showed that the therapy, along with glucocorticoids, helped more EGPA patients achieve and stay in disease remission than glucocorticoids alone.
To gather evidence of Nucala’s real-world safety and effectiveness, researchers in Spain retrospectively analyzed data from 30 EGPA patients treated with Nucala across 13 rheumatology centers in that country. These adults were recruited from January 2019 to January 2023.
“So far as we know, this is the largest Spanish [group] of patients with EGPA treated with [Nucala] in real practice,” the researchers wrote.
Nearly half of patients were in remission after 6 months of treatment
Slightly over half (53.3%) were men, and their median age at diagnosis was 52. All had asthma and 86.7% had symptoms affecting the nose and the air-filled cavities around the nose. Four patients (13.3%) had interstitial lung disease, referring to conditions marked by inflammation and scarring in the lungs.
About half of the patients were positive for ANCAs, the self-reactive antibodies that cause most cases of AAV but are less frequently detected in EGPA.
Patients were treated daily with 50 mg of prednisone, a glucocorticoid, at diagnosis, and nearly one-third (30%) required into-the-vein administration of methylprednisolone, another glucocorticoid. Nearly two-thirds (63.3%) needed at least one immunosuppressive medication, with the most common being cyclophosphamide.
Nucala was started at a mean of about four years after diagnosis. More than half of the patients (53.3%) were given the approved dose of 300 mg once a month. Another 43.3% of patients started treatment at 100 mg once a month, and one patient received Nucala at 200 mg. A total of 12 people (40%) also were treated with an immunosuppressant.
Patients were followed for a mean of 16 months (nearly 1.5 years).
The median Birmingham Vasculitis Activity Score — a measure of disease activity in which higher values indicate more severe disease — fell significantly, dropping from 6 before Nucala’s start to 3 after one month of treatment.
The median score of the Vasculitis Damage Index, a measure of organ damage, was calculated in 27 patients (90%), and remained stable across follow-up. This score increased in four patients (15.4%), indicating greater organ damage.
Nearly half (46.7%) achieved clinical remission after six months of treatment, with four patients (13.3%) deemed as nonresponders, according to a physician’s global assessment.
Almost 77% of patients on Nucala able to lower their glucocorticoid dose
After three months of treatment, patients showed a marked reduction in eosinophil counts and blood levels of C-reactive protein, a marker of generalized inflammation.
Daily doses of prednisone fell from 18.7 mg to 2.4 mg after starting with Nucala. The median glucocorticoid dose was decreased in 76.7% of patients, with 53.3% suspending that treatment completely.
At last observation, 80% of patients were still using Nucala. None reported severe adverse effects, local reactions, or serious infections during the treatment.
“Our data on the real practice use of [Nucala] in EGPA suggests that this drug has good efficacy, is safe and reduces the dependence on glucocorticoids or even their complete withdrawal,” the researchers wrote. “Furthermore, it appears to prevent the organic damage progression associated with this disease.”
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