Medical-AI trial: personalizing rituximab dosing with AI — optimizing treatment in membranous nephropathy (a leading cause of nephrotic syndrome) (NCT06341205)

1Membranous nephropathy and rituximab

Membranous nephropathy is an autoimmune disease in which the kidney filter (the glomerulus) is attacked by the immune system and large amounts of protein leak into the urine; it is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults. Its course varies greatly from person to person, from spontaneous remission to progression to chronic kidney disease.

In recent years, discovery of the autoantibody PLA2R1 supported a targeted approach, making rituximab, which depletes B cells, a safe and effective first-line drug. Yet a challenge remains: up to 40% of patients do not respond to a first course.

2An interventional study personalizing dosing

This interventional study examines whether the use of rituximab can be personalized with AI. Per the registry summary, taking into account each patient differing condition (in the nephrotic state, drug handling also changes), it aims to optimize dosing with an AI-based personalized protocol. The primary outcome is clinical remission (complete or partial) six months after starting rituximab. The size is 120, and it is recruiting.

3Four in ten do not respond

The same drug works for some patients and not others. What this study takes as its starting point is that the share is known concretely.

Membranous nephropathy is the most common cause of nephrotic syndrome in non-diabetic adults, with rituximab, which depletes B cells, established as first-line therapy. In the nephrotic state pharmacokinetics are disturbed — drug is lost into the urine, among other effects — so a uniform dose is hard to optimise.

Adjusting dosing per patient points toward precision medicine using an expensive, powerful biologic at the dose and timing that work.