An antibody-based drug triggers rare inflammatory eye problems in macular degeneration patients (Brolucizumab causes immune problems leading to blindness in 2% of users)

A drug approved in 2019 for macular degeneration apparently caused rare retinal side effects because of its interactions with the human immune system, two new studies have concluded.

The drug, a monoclonal antibody called brolucizumab, was developed for an eye condition known as wet age-related macular degeneration, or simply, AMD.

Reports emerged a few months after its launch noting rare retinal disorders in a small percentage of patients treated with the drug. These side effects impacted an estimated 2.1% of patients.

"In 2020, rare cases of retinal vasculitis and/or retinal vascular occlusion were reported, often during the first few months after treatment initiation, consistent with a possible immunologic pathobiology," Karle noted.

Retinal vasculitis is an inflammatory condition affecting blood vessels of the retina. Retinal vascular occlusion, on the other hand, is caused by a blockage in veins moving blood away from the retina, leading to rapid and severe loss of visual acuity.

To understand why the medication didn't work for some patients, Karle compared serum samples.

Serum analyses revealed that an immune response against brolucizumab was a prerequisite for both side effects because only patients with retinal vasculitis or retinal vascular occlusion showed strong T cell responses to the treatment. Patients' immune systems were attacking their retinas after treatment with the drug.

In a second study Dr. Jeffrey Kearns and colleagues adopted a translational approach.

"The presence of antidrug antibodies in these patients led to the initial hypothesis that immune complexes could be key mediators," wrote Kearns.

Kearns studied brolucizumab's effects in a model that mimicked conditions in the eye.

Factors included a linear epitope on the drug shared with gut bacterial proteins, and the appearance of non-native derivatives of brolucizumab after 13 weeks. These manifestations led to the formation of immune complexes between brolucizumab and anti-drug antibodies.

Be aware there could be blindness from this specific immunotherapy, due to an immune attack on your eyes.

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2 posted on 04/04/2023 8:38:22 PM PDT by ConservativeMind (Trump: Befuddling Democrats, Republicans, and the Media for the benefit of the US and all mankind.)

So a drug developed to slow down possible macular degeneration blindness, sped up the process.

Did I get that right?

3 posted on 04/04/2023 8:49:15 PM PDT by CaptainK ("If life's really hard, at least its short")

Yes, well, created a different way to quickly go blind.

4 posted on 04/04/2023 9:10:37 PM PDT by ConservativeMind (Trump: Befuddling Democrats, Republicans, and the Media for the benefit of the US and all mankind.)

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