Long-term Nucala found well tolerated as EGPA treatment: Data
Injection therapy reduced, even eliminated corticosteroid use in patients
Long-term treatment with Nucala (mepolizumab) — approved for use in EGPA, or eosinophilic granulomatosis with polyangiitis, the rarest type of ANCA-associated vasculitis — appears to be well tolerated by most patients, and was seen to reduce or even eliminate corticosteroid use.
That’s according to new data from an open-label extension study (NCT03298061) involving 100 adults initially enrolled in the Phase 3 MIRRA clinical trial (NCT02020889), completed in 2016. Data from that trial had supported Nucala’s approval the following year in the U.S. for treating EGPA. However, the researchers noted that “systematic reports of long-term [Nucala] use in EGPA are limited.”
This study, titled “Long-Term Safety and Efficacy of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis,” had assessed Nucala’s safety and efficacy over the long term in people with EGPA. It was funded by GlaxoSmithKline, which markets Nucala, and published in the journal Arthritis & Rheumatology. Four of the eight study authors are employed by the company.
Overall, “these results support a positive long-term safety profile as well as sustained efficacy of prolonged use of [Nucla] in the treatment of EGPA,” the researchers wrote.
Researchers note ‘pressing need’ for corticosteroid-sparing therapies
Like other types of AAV, EGPA causes blood vessels of small size to become inflamed, resulting in damage to the body’s organs. In EGPA, clumps of white blood cells called eosinophils help drive the damaging inflammation to small blood vessels.
EGPA treatment “has historically relied on oral corticosteroids (OCS),” the researchers wrote, but for some patients, this isn’t enough to keep the disease under control. Some individuals treated with corticosteroids experience cycles of remission and relapse, in which periods of recovery are followed by a worsening of symptoms or the onset of new ones.
“As prolonged use of OCS increases the risk of adverse effects overtime and is associated with acute infections, there is a pressing need for effective treatment strategies that spare OCS,” the researchers wrote.
Nucala is approved in the U.S. and Canada as an add-on to standard care with glucocorticoids in adults with EGPA. In the European Union, it’s approved for patients, ages 6 and older, with relapsing or treatment-resistant EGPA.
Administered via a subcutaneous, or under-the-skin, injection once every four weeks, the therapy works by blocking the action of interleukin-5 (IL-5), a signaling molecule that acts on eosinophils, helping them grow in number and survive. By reducing the number of eosinophils in the bloodstream, Nucala reduces inflammation and eases symptoms of EGPA.
The approvals were based on nearly one year of data from the international Phase 3 MIRRA trial, which had involved 136 adults with relapsing or treatment-resistant EGPA. The study results showed that patients on Nucala plus glucocorticoids were more likely to achieve disease remission and stay in remission relative to those given glucocorticoids alone.
Multiple real-world studies have shown that Nucala can reduce the risk of relapse and prolong survival, while reducing the need for corticosteroids. However, reports of the effects of long-term Nucala treatment remain few.
No new safety concerns seen with use of approved EGPA treatment
Now, the researchers analyzed data from the 100 patients given Nucala in MIRRA’s open-label extension, or OLE, study. Eligible patients were those who still required a daily dose of 5 mg of oral corticosteroids (prednisolone or equivalent) to control their disease within six months after their last visit during MIRRA.
The patients’ mean age at the start of the OLE study was 49.6, and slightly more than half were women (57%). Most (73%) completed the study. The most common reasons for study withdrawal were patient decision (10 patients), physician decision (seven patients), and lack of efficacy (six patients).
Altogether, the participants received Nucala, on top of standard care, for a median of 27 months, or a little longer than two years, and for as long as 89 months, or nearly 7.5 years.
Nearly all patients (98%) experienced at least one adverse event while on Nucala; in 43%, these were deemed related to the therapy. The most commonly reported Nucala-related adverse event was reactions at the injection site (17%), followed by infections (15%).
Serious side effects occurred in 38% of patients, and were considered to be related to Nucala in 6%.
Overall, these findings suggested that Nucala’s safety profile “was consistent with that seen in MIRRA, and prior studies in … EGPA, with no new safety concerns identified,” the researchers wrote.
This OLE study of treatment with [Nucala] for patients from MIRRA adds to the body of evidence on the long-term safety and [oral corticosteroids]-sparing effects of [Nucala].
In addition, the median daily dose of corticosteroids dropped from 10 mg at the OLE study’s start to 5 mg at the final three-month period of available data (study exit). The proportion of patients taking more than 7.5 mg per day went down from 75% to 32%, and 28% of patients were able to stop corticosteroids completely by study exit.
“This OLE study of treatment with [Nucala] for patients from MIRRA adds to the body of evidence on the long-term safety and OCS-sparing effects of [Nucala],” the researchers wrote, noting its “positive long-term benefit [to] risk profile.”
Further studies “are needed to examine the ability of [Nucala] to help achieve reduction of other immunosuppressive drugs, prevent organ damage associated with long-term OCS use, and allow patients to achieve complete remission,” the team concluded.
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