Infliximab Successfully Treats Boy’s GPA Respiratory Symptoms: Report

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Infliximab successfully led to the remission of respiratory symptoms in a 15-year-old boy with steroid-resistant granulomatosis with polyangiitis (GPA), a type of ANCA-associated vasculitis (AAV), according to a case report.

More studies are needed to determine the treatment’s safety profile in children, the researchers noted.

The report, “Infliximab therapy of relapsing tracheal stenosis in a pediatric patient with granulomatosis with polyangiitis: a case report,” was published in the Journal of Medical Case Reports

Respiratory tract symptoms that affect the ear, nose, and throat, accompanied by clumps of immune cells in the affected areas (granulomas), are usually what occur first in children with GPA. Left untreated, the disease often progresses to the lungs and kidneys.

A high dose of steroids is usually administered to push the autoimmune disease into remission. A lower dose of steroids in combination with immunosuppressants like azathioprine, methotrexate, or rituximab may be used to maintain remission.

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It’s been proposed that therapies targeting the inflammatory molecule tumor necrosis factor-alpha (TNF-a), such as infliximab, may hold promise for those who don’t respond well to other treatments.

In this case report, a 15-year-old boy arrived at the hospital in March 2020 with a fever, recurring ear inflammation, and ulcers on his face and nose. A nasal biopsy showed granulomas associated with tissue death. Imaging tests showed artery inflammation in his spleen, but no other organs were affected.

The boy had high levels of C-ANCA/PR3 antibodies (360 units per milliliter (U/mL); upper normal limit: 20 U/mL). Of note, PR3 antibodies are present in about 75–90% of GPA patients.

Clinicians determined the boy met the criteria for GPA. He was treated with a high dose of steroids for three days to eliminate symptoms, followed by maintenance therapy, which included low-dose steroids and azathioprine. Antibiotics and an anticoagulant (blood thinner), were also administered to treat the spleen.

In May 2020, the boy was taken off of all medications, except azathioprine, due to his remission. He returned to the hospital in September 2020 with shortness of breath at rest, noisy breathing, and hearing loss.

A lung function test showed his airways were markedly obstructed and an MRI scan revealed airway narrowing between the vocal cords and the air tubes carrying oxygen to the lungs (trachea), a condition called subglottic stenosis. His PR3 antibody levels were at 93 U/mL.

High-dose steroids were again administered, followed by a course of rituximab. While clinical tests showed improvements, the boy said he still had shortness of breath and signs of stenosis were still observed.

To open his airways, the clinicians added inhaled steroids and a bronchodilator (formoterol) to the treatment regimen.

Nearly a year after his first visit, the boy’s respiratory symptoms again worsened in February 2021. Lung function tests and an MRI scan showed reduced lung capacity and subglottic stenosis had returned.

A biopsy from the airways showed significant infiltration of neutrophils, immune cells known to be overactive in AAV. This time, the boy did not respond to high doses of steroids.

A decision was made to administer infliximab once every two weeks for six weeks to induce remission, followed by once every four weeks to maintain it. The boy continued to receive azathioprine in the meantime.

The treatment was successful and his respiratory symptoms resolved. At his last follow-up in May 2021, the boy was in complete clinical remission.

According to clinicians, TNF-alpha may help recruit neutrophils to the airways, thereby playing an important role in forming granulomas that are often observed in the respiratory tract of GPA patients, making inhibiting the molecule with infliximab make sense.

“Our case report supports the potential of the additional use of infliximab in steroid and [rituximab] refractory [treatment-resistant] cases, yet there is a strong need for further evidence for the safe use of [infliximab] in children,” the researchers wrote.