Long-term Nucala safely eases EGPA symptoms: Real-word study

Treatment also reduced need for corticosteroids for over 30% of patients

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Treatment with Nucala (mepolizumab) for three or more years is safe, and was effective at easing symptoms and reducing the risk of relapse in people with eosinophilic granulomatosis with polyangiitis (EGPA), the most rare type of ANCA-associated vasculitis (AAV), a real-world study in Japan shows.

Further, the need for oral corticosteroids was reduced among more than one-third of patients after three years, with a sizeable number of study participants no longer using a high dose of steroid hormones by the end of an interim 48-week analysis.

“These results provide further evidence of the clinically relevant, real-world benefits of [Nucala] treatment for patients with EGPA in Japan, both for symptom control and as an [oral corticosteroid]-sparing treatment,” the researchers wrote, adding that new “safety data … is consistent with the known safety profile” of the approved medication.

The study, “Real-world safety and effectiveness of mepolizumab for patients with eosinophilic granulomatosis with polyangiitis in Japan: A 48-week interim analysis of the MARS study,” was published in the journal Modern Rheumatology.

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Analysis focused on treatment’s safety and effectiveness ‘beyond 96 weeks’

EGPA is the rarest type of AAV, a group of autoimmune disorders characterized by inflammation in small blood vessels. That inflammation eventually damages tissues and organs in the body, and causes a wide array of disease symptoms.

This particular form of AAV is characterized by high numbers of immune cells called eosinophils in the blood and symptoms that mostly affect the lungs and gastrointestinal tract.

Nucala, marketed by GlaxoSmithKline (GSK), is an add-on therapy approved for certain EGPA patients in the U.S. and Japan, as well as in the European Union. It works to reduce eosinophil levels by blocking the IL-5 signaling molecule that promotes the cells’ growth, maturation, and survival.

The treatment’s approvals were based on nearly one year of data (48 weeks) from the international Phase 3 MIRRA clinical trial (NCT02020889). That study, which spanned three continents, involved 136 adults with relapsing or treatment-resistant EGPA.

Participants were randomly assigned to receive subcutaneous or under-the-skin injections of either Nucala or a placebo every four weeks, in addition to standard AAV treatment — corticosteroids with or without immunosuppressants.

The results showed that Nucala was associated with a greater proportion of patients achieving disease remission and with longer accrued time in remission relative to the placebo.

Interim data from a post-marketing surveillance study in Japan — where EGPA patients were followed for 96 weeks, or nearly two years, after starting Nucala — supported the medication’s real-world safety and efficacy. Specifically, 48 weeks of treatment were shown to lead to a reduction in symptoms and in corticosteroid dependence.

However, the long-term safety and effectiveness of Nucala in “patients with EGPA beyond 96 weeks, either in Japan or worldwide,” has never been assessed, the researchers noted.

With this in mind, scientists at GSK along with a colleague in Japan conducted an interim 48-week analysis of the GSK-sponsored observational MARS study (NCT04551989). MARS is assessing the long-term, real-world safety and efficacy of Nucala in 118 adults with EGPA.

These patients’ mean age was 61.9, 55% were women, and the majority had asthma (76%). All had been treated with Nucala continuously for at least 96 weeks by the start of the MARS study. Two patients were MIRRA participants and had received Nucala for as long as 6.5 years.

This analysis showed that, during nearly one year of treatment within the MARS study — the third or more year of treatment overall — 34 patients (29%) patients experienced an adverse event. Serious adverse events were reported in 15 patients (13%), with the most common being gastrointestinal disorders, infections and infestations, and tumors, both cancerous and non-cancerous.

None of the adverse events or the serious adverse events were deemed to be linked to Nucala.

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Fewer hospitalizations, ER visits also seen for patients on Nucala

According to the analysis’ findings, the median daily use of oral corticosteroids in the year prior to the first dose of Nucala was of 6.9 mg/day. Such corticosteroid use was reduced to 3 mg/day after at least two years of treatment — the start of the MARS study — and to 2 mg/day after another year within MARS.

The number of patients not relying on corticosteroids increased from 8% before Nucala to 32% after two or more years of treatment — and further, to 38% after another year of its use. Additionally, the proportion of patients using a high dose of corticosteroids, specifically more than 7.5 mg/day, was reduced from 44% to 11% at MARS’ start, and remained low by week 48 (10%-14%).

“Patients had reduced [oral corticosteroid] use … with higher overall proportions of patients not using [steroid hormones] and lower doses,” the researchers wrote.

The proportion of patients without clinical symptoms increased from 6% prior to Nucala use to 27% after at least two years of treatment. After another year of treatment, that proportion increased to 33%, or about one-third of participants.

In parallel, the proportion of patients with clinical symptoms affecting any of the nine major organ systems — including the skin, cardiovascular, and nervous system — dropped from 94% to 73% at MARS’ start and to 67% at week 48 of follow-up.

Patients had reduced [oral corticosteroid] use … with higher overall proportions of patients not using [steroid hormones] and lower doses.

During the nearly one year of treatment within the MARS study, six patients (5%) had an EGPA relapse.

Overall, however, “reduced EGPA-related hospitalisations and ER/unscheduled visits were also observed in this study,” the researchers noted.

Specifically, the annualized rate of either EGPA-related hospitalizations or EGPA-related emergency room or unscheduled visits per patient dropped by about 10 times after 48 weeks in MARS, the data showed.

Also, the number of eosinophils was markedly reduced with long-term Nucala treatment. It dropped from a mean of 169.4 cells per microliter (mcl) of blood before treatment to 19.6 cells/mcl after two or more years of treatment, and remaining stable after an additional year (19.4 cells/mcl).

Overall, “the results of [Nucala] treatment for [at least] 144 weeks [2.8 years] … were consistent with the known safety profile and allowed [oral corticosteroid] dose reduction while improving disease control versus pre-treatment among patients with EGPA,” the researchers concluded.