IgG4-Related Disease: New Experimental Treatment Strategies

IgG4-related disease (IgG4-RD) is a chronic inflammatory disease that, for reasons not yet fully understood, causes tumor-like lesions affecting various tissues and organs throughout the body.

To date, there are only 2 treatment options for people with this disease:

• corticosteroids: effective, but associated with significant side effects;
• biologic drugs such as rituximab and inebilizumab: these work by eliminating B lymphocytes, the cells responsible for the disease, but expose patients to a risk of infections and require repeated intravenous infusions in hospital.

The study suggests that there may be a third option. Researchers have shown that obexelimab significantly reduces the risk of disease relapse compared with placebo while allowing the use of much lower doses of corticosteroids. Obexelimab is also administered by subcutaneous injection, providing greater flexibility in treatment, for example in the event of fever or before surgery, when therapy needs to be temporarily discontinued.

IgG4-related disease is driven by the activity of B lymphocytes, immune system cells that produce the IgG4 antibodies involved in the disease. Currently available therapies work by completely eliminating these lymphocytes from the circulation. Obexelimab, on the other hand:

• binds to their surface;
• reduces their ability to produce antibodies without destroying them.

This difference has an important practical implication: the effects of obexelimab wear off more quickly once treatment is discontinued, because its half-life, the time required for its concentration in the blood to decrease by half, is shorter. This makes it easier to temporarily suspend treatment when necessary, for example in the presence of an infection. With currently available biologic therapies, by contrast, the immunosuppressive effect lasts longer, with a risk of infection that may increase over time.

“This new molecule helps address needs that have so far remained unmet for people with IgG4-related disease: it prevents relapses, is easier to administer and reduces the need for corticosteroids,” explains Emanuel Della Torre.

Researchers are now working to confirm the benefits of obexelimab over a longer period of time.

Ospedale San Raffaele was the first center in Italy to focus specifically on IgG4-related disease, establishing a dedicated IgG4-Related Disease Clinic (IgG4-RD Clinic) coordinated by Professor Della Torre within the Immunology, Rheumatology, Allergy and Rare Diseases Unit.

Given the systemic nature of the disease, the clinic coordinates a multidisciplinary team of specialists in:

• gastroenterology;
• hepatology;
• otolaryngology;
• ophthalmology;
• pulmonology;
• neurology;
• pancreatic, hepatobiliary and thoracic surgery.

All cases are discussed during dedicated multidisciplinary meetings, with the aim of defining the most appropriate and personalized diagnostic and treatment pathway for each patient.

The clinic offers patients the opportunity to:

• obtain rare disease exemption status;
• access clinical and translational research projects;
• participate in clinical trials and studies involving innovative therapies;
• contribute to the development of guidelines and documents aimed at improving the quality of life of people with IgG4-RD.