Allergic bronchopulmonary aspergillosis symptoms improve with mepolizumab

Key takeaways:

• This case study indicates reduced steroid use with biologic treatment.
• Treatment reduced IgE levels and radiographic symptoms.
• Mepolizumab and itraconazole has kept the patient symptom-free for 8 months.

BOSTON — Symptoms improved with mepolizumab after treatment with omalizumab failed for a patient with asthma who developed allergic bronchopulmonary aspergillosis, according to a poster presented at the CHEST Annual Meeting.

Biologic treatment may prevent the need for long-term steroids for similar patients, Gwendolyn Kuzmishin, DO, a PGY-3 in the department of internal medicine at Cleveland Clinic Akron General, told Healio.

“This was a really interesting case,” Kuzmishin said.

The patient, aged 70 years, was a man with a history of severe persistent asthma, including pulmonary function tests indicating a mild obstructive defect and a significant bronchodilator response. The history also included allergic rhinitis and hyperlipidemia.

“He came in with fatigue, worsening wheezing, cough, and then these recurrent what they thought were pneumonia and respiratory tract infections,” Kuzmishin said.

Upon admission, the CT chest scan without contrast revealed infiltrate with a “crazy paving pattern,” Kuzmishin said. There also was central nodularity and mediastinal lymphadenopathy, including mediastinal lymph nodes of up to 1.1 cm each.

The researchers categorized his bronchoscopy as remarkable for normal lymph node biopsy. The bronchoalveolar lavage (BAL) indicated mixed cellularity, and his CD4:CD8 ratio was elevated, the researchers continued.

“He had about 12% eosinophils on his BAL,” Kuzmishin said. “At that time, they just decided to treat it as an eosinophilic pneumonia.”

A high-dose empiric steroid course then followed.

“Within 2 weeks, he reports complete resolution of his symptoms,” Kuzmishin said.

The interstitial changes were cleared in a follow-up chest CT without contrast at 4 months, with resolved areas of ground glass opacities and central nodularity.

“We have complete radiographic resolution of his symptoms, and that’s just on steroids,” Kuzmishin said. “He remained on steroids, slowly tapering them, over the course of a year, and then he was actually off steroids for about 2 months when he had a complete recurrence of symptoms.”

The physicians repeated the workup, with a 1,381 kU/L IgE level indicating peripheral eosinophilia. The antinuclear antibody, antineutrophil cytoplasmic antibody, cytoplasmic, and peripheral antineutrophil cytoplasmic antibody tests all were negative.

Also, the “crazy paving pattern” reappeared in the CT chest scans, and there was severe and extensive sinusitis with polyposis in the CT sinus scans, the researchers said. The aspergillus IgE levels were 37.4 kU/L as well, leading the physicians to diagnose the patient with allergic bronchopulmonary aspergillosis (ABPA).

“We decided to start him on itraconazole, some antifungal therapy and systemic steroids,” Kuzmishin said. “On that combination therapy, he had both clinical improvement in the symptoms and then we also saw radiographic improvement and biologic marker improvement.”

The patient’s IgE level fell to 254 kU/L, and his aspergillus IgE level fell to 14.5 kU/L.

“Then we determined that this patient was somebody that was definitely going to benefit from ongoing therapy but didn’t want to keep him on steroids, so that’s when we were starting to think about biologic therapy,” Kuzmishin said. “There are a lot of emerging case reports and some meta-analyses about biologic therapy specifically in ABPA.”

Kuzmishin also noted that ABPA is a hypersensitivity reaction to aspergillus.

The physicians began treatment with omalizumab (Xolair; Genentech, Novartis) in conjunction with itraconazole while weaning the patient off steroids.

“Omalizumab is a monoclonal antibody against the high affinity receptor on IgE, so basically we’re targeting that hypersensitivity pathway, like mast cells,” Kuzmishin said. “Essentially what we’re doing is disrupting that mast cell degranulation, that hypersensitivity pathway.”

At 18 months, the patient’s pulmonary function testing indicated interval improvements compared with baseline. Also, itraconazole was discontinued after 9 months of antifungal therapy, and the patient continued with omalizumab and a reduced course of inhaled corticosteroids.

But after 14 months of omalizumab, including 9 months of itraconazole, symptoms completely relapsed. IgE levels increased to 1,571 kU/L, and previous radiographic findings such as poorly defined upper lobe infiltrates recurred in chest X-rays.

“What do we do? Is this an exacerbation? Or do we consider this treatment failure?” Kuzmishin said. “We decided to transition him to mepolizumab.”

The symptoms resolved again with mepolizumab (Nucala, GSK), which targets IL-5 and prevents it from binding to eosinophils, and itraconazole.

“He’s been symptom-free for 8 months,” Kuzmishin said.

Itraconazole eliminates aspergillosis by reducing the amount of aspergillus in the airway, Kuzmishin said, but biologics such as omalizumab and mepolizumab take a different approach.

“This is more trying to target the pathway, the hypersensitivity reaction, rather than what’s causing the hypersensitivity reaction,” she said.

However, this indication is off label for these biologics despite some growing research in this area, she added.

“They don’t technically have FDA approval for ABPA,” she said. “These biologics are probably helpful in these patients, but there’s not any great guidelines.”

Overall, the researchers said there is a paucity of data for guiding long-term therapy that spares steroid use for patients with ABPA, with a lack of large-scale randomized controlled trials and consensus guidelines addressing biologic treatment.

“How do we define what markers we are going to use for an exacerbation? Is the disease worsening?” Kuzmishin said. “There’s just a lot that needs to be done in this space.”

The researchers advised clinicians to consider seronegative eosinophilic granulomatosis with polyangiitis among patients who have this clinical syndrome, in addition to calling for a trial of mepolizumab in treating these patients.

“We’re seeing a lot more disease recurrence,” Kuzmishin said. “This is affecting a lot of asthmatic patients and also a lot of patients with cystic fibrosis, patients with bronchiectasis.”

Treatment failures such as this in addition to exacerbations also are emerging as patients live longer with these diseases, she continued.

“How can we keep these people off steroids long term, and how can we prevent ABPA from progressing to pulmonary fibrosis in these patients?” she said.

For more information:

Gwendolyn Kuzmishin, DO, can be reached at kuzmisg3@ccf.org.