Meeting News

Emerging therapies show renewed ‘hope on the horizon’ for EGPA

Anisha Dua

CHICAGO — The emergence of interleukin-5 inhibitors and omalizumab as potential treatments for eosinophilic granulomatosis with polyangiitis could mean a breakthrough for a patient population that is rarely included in large randomized clinical trials, and has had to make do with prednisone and cyclophosphamide as a first-line treatment, according to a presenter at the 2019 Interdisciplinary Autoimmune Summit.

“EGPA patients have not been consistently included in these larger randomized controlled trials that have evaluated therapy for ANCA-associated vasculitis, so we have to extrapolate treatment recommendations based on those trials along with cohort studies in EGPA,” Anisha Dua, MD, MPH, associate director at the Northwestern University Vasculitis Center, told attendees. “We have to keep in mind that this is a risk.”

“In addition, in life-threatening forms of the disease, cycloheximide and steroids are still first line,” she added. “The toxicities of our therapies, and the disease itself, can result in significant morbidity.”

Steroids are effective and work quickly for patients with EGPA and life-threatening conditions, such as serious eye involvement or mononeuritis, according to Dua. However, 85% of patients with EGPA require long-term prednisone doses of more than 7.5 mg each day to control their asthma, rhinitis and arthralgias, she added.

Meanwhile, the side effects of steroids can be “monstrous,” Dua said. They include infection, osteoporosis, cataracts, avascular necrosis, diabetes, gastritis, anxiety, skin and hair thinning and weight gain. In addition, Dua stated although cyclophosphamide with prednisone has, in general, greatly improved morbidity and mortality, research has shown that 50% of patients who respond to initial therapy eventually relapse within 5 years.

For these reasons, physicians and researchers have been aiming for a targeted EGPA therapy. This search led them to mepolizumab (Nucala, GlaxoSmithKline), a humanized monoclonal antibody that inhibits IL-5, which is elevated in patients with EGPA and is associated with disease activity.

According to Dua, the MIRRA trial, which studied mepolizumab in 136 relapsing or refractory patients with EGPA, was “groundbreaking.”

“It is one of the few randomized controlled trials in EGPA,” she said. “In terms of emerging therapies, that really was a breakthrough for us, in terms of having something new at our disposal that has actually been studied in the population we are trying to treat.”

The results of the 52-week trial, published in the New England Journal of Medicine in 2017, found that mepolizumab, when administered to patients receiving stable daily oral corticosteroid therapy resulted in more weeks in remission, as well as a higher proportion of patients achieving remission, compared with placebo. This allowed for a reduction in glucocorticoid use.

In December 2017, the FDA approved mepolizumab as an add-on therapy for maintenance in EGPA.

According to Dua, other IL-5 inhibitors current being studied for EGPA include reslizumab (Cinqair, Teva) and benralizumab (Fasenra, AstraZenica), which specifically targets the IL-5 receptor-alpha-chain and is currently the focus of phase 2 trials.

In addition, omalizumab (Xolair, Genentech), which blocks immunoglobulin E, another target for EPGA treatment, has also shown some promise. In a study of 18 patients with EGPA, the drug helped control asthma, improve pulmonary function tests and reduce the need for steroids, with a significant decrease in the use of prednisone over 1 year.

“This was a tiny trial, but this is a rare disease, so we take what we can — at least until we can get more information,” Dua said. “New targeted therapies are being investigated, so we do have some hope on the horizon.” – by Jason Laday

Reference:
Dua A. Raising Awareness of EGPA: Optimal Diagnostic, Therapeutic and Team-Based Care Strategies. Presented at: Interdisciplinary Autoimmune Summit; April 5-7, 2019; Chicago.

Disclosure: Dua reports consulting and speaking fees from AbbVie, as well as research grants from Chemocentryx.

Anisha Dua

CHICAGO — The emergence of interleukin-5 inhibitors and omalizumab as potential treatments for eosinophilic granulomatosis with polyangiitis could mean a breakthrough for a patient population that is rarely included in large randomized clinical trials, and has had to make do with prednisone and cyclophosphamide as a first-line treatment, according to a presenter at the 2019 Interdisciplinary Autoimmune Summit.

“EGPA patients have not been consistently included in these larger randomized controlled trials that have evaluated therapy for ANCA-associated vasculitis, so we have to extrapolate treatment recommendations based on those trials along with cohort studies in EGPA,” Anisha Dua, MD, MPH, associate director at the Northwestern University Vasculitis Center, told attendees. “We have to keep in mind that this is a risk.”

“In addition, in life-threatening forms of the disease, cycloheximide and steroids are still first line,” she added. “The toxicities of our therapies, and the disease itself, can result in significant morbidity.”

Steroids are effective and work quickly for patients with EGPA and life-threatening conditions, such as serious eye involvement or mononeuritis, according to Dua. However, 85% of patients with EGPA require long-term prednisone doses of more than 7.5 mg each day to control their asthma, rhinitis and arthralgias, she added.

Meanwhile, the side effects of steroids can be “monstrous,” Dua said. They include infection, osteoporosis, cataracts, avascular necrosis, diabetes, gastritis, anxiety, skin and hair thinning and weight gain. In addition, Dua stated although cyclophosphamide with prednisone has, in general, greatly improved morbidity and mortality, research has shown that 50% of patients who respond to initial therapy eventually relapse within 5 years.

For these reasons, physicians and researchers have been aiming for a targeted EGPA therapy. This search led them to mepolizumab (Nucala, GlaxoSmithKline), a humanized monoclonal antibody that inhibits IL-5, which is elevated in patients with EGPA and is associated with disease activity.

According to Dua, the MIRRA trial, which studied mepolizumab in 136 relapsing or refractory patients with EGPA, was “groundbreaking.”

“It is one of the few randomized controlled trials in EGPA,” she said. “In terms of emerging therapies, that really was a breakthrough for us, in terms of having something new at our disposal that has actually been studied in the population we are trying to treat.”

The results of the 52-week trial, published in the New England Journal of Medicine in 2017, found that mepolizumab, when administered to patients receiving stable daily oral corticosteroid therapy resulted in more weeks in remission, as well as a higher proportion of patients achieving remission, compared with placebo. This allowed for a reduction in glucocorticoid use.

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In December 2017, the FDA approved mepolizumab as an add-on therapy for maintenance in EGPA.

According to Dua, other IL-5 inhibitors current being studied for EGPA include reslizumab (Cinqair, Teva) and benralizumab (Fasenra, AstraZenica), which specifically targets the IL-5 receptor-alpha-chain and is currently the focus of phase 2 trials.

In addition, omalizumab (Xolair, Genentech), which blocks immunoglobulin E, another target for EPGA treatment, has also shown some promise. In a study of 18 patients with EGPA, the drug helped control asthma, improve pulmonary function tests and reduce the need for steroids, with a significant decrease in the use of prednisone over 1 year.

“This was a tiny trial, but this is a rare disease, so we take what we can — at least until we can get more information,” Dua said. “New targeted therapies are being investigated, so we do have some hope on the horizon.” – by Jason Laday

Reference:
Dua A. Raising Awareness of EGPA: Optimal Diagnostic, Therapeutic and Team-Based Care Strategies. Presented at: Interdisciplinary Autoimmune Summit; April 5-7, 2019; Chicago.

Disclosure: Dua reports consulting and speaking fees from AbbVie, as well as research grants from Chemocentryx.

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