Treatment options for IgG4-related disease

Immunoglobulin G4-related disease (IgG4-RD) is a complex immune system condition that causes organ inflammation, tumor-like lesions, and scarring. It can affect many organs in the body, such as the pancreas, kidneys, and salivary glands and the area around the eyeballs.

The symptoms and complications a person may experience will depend on which organs the disease affects.

While there’s no definitive cure for IgG4-RD, healthcare professionals consider it highly treatable, and many people notice improvement within days or weeks of starting medications.

The goal of treatment is to reduce inflammation and bring on remission, a state in which there are no active signs of the disease. To help reduce the chances of irreversible organ damage, people with an IgG4-RD diagnosis should receive treatment even if they have no symptoms.

This article provides an overview of the most common treatments for IgG4-RD and the situations in which doctors may recommend them.

Corticosteroid medications mimic the body’s natural steroid hormones. They work by decreasing inflammation and suppressing immune responses.

In IgG4-RD, corticosteroids — particularly prednisone — are a cornerstone of treatment. Prednisone is a first-line therapy and is one of the first medications a doctor may prescribe.

The dose will vary depending on the severity of symptoms, but most standard courses run 2 to 4 weeks, and a person will then taper off the medication over 2 to 3 months.

Corticosteroids can help reduce symptoms throughout the body, and their rapid effects make them ideal for treating inflammation and immune dysfunction in vulnerable organs such as the pancreas, kidneys, and lymph nodes.

Immunosuppressants reduce immune system activity in IgG4-RD, helping to decrease inflammation and prevent organ damage.

Doctors may sometimes add immunosuppressant medication to an IgG4-RD treatment plan with a corticosteroid to limit the amount of prednisone a person takes. In this role, the immunosuppressant is called a steroid-sparing immunosuppressant.

Doctors may decide to prescribe an immunosuppressant alongside a corticosteroid at first if a person has a high chance of relapse or has other existing risk factors, such as other medical conditions or multi-organ disease.

In rare cases, a doctor may recommend immunosuppressants as a substitute for corticosteroids if a person cannot tolerate corticosteroids or is at high risk of serious side effects.

While many types of immunosuppressants are available, disease-modifying antirheumatic drugs (DMARDs) are the type doctors most commonly prescribe to treat IgG4-RD.

Targeted therapies work by altering a specific step in a disease process to prevent disease progression.

In IgG4-RD, doctors prescribe targeted therapies to lower the number of B cells circulating in the bloodstream. B cells are a type of immune cell. In IgG4-RD, overactive B cells drive inflammation and turn into plasmablasts, which build up in tissue and contribute to fibrosis (scarring).

Targeted medications can reduce B-cell activity and break the cycle of immune dysfunction that underlies IgG4-RD.

Currently, inebilizumab-cdon (Uplizna) is the only targeted therapy that has received a Breakthrough Therapy Designation from the Food and Drug Administration (FDA) for the treatment of IgG4-RD. Several others are in clinical trials.

Uplizna is a monoclonal antibody drug that targets a specific protein site on B cells (CD19) and flags them for the immune system to destroy.

Researchers are studying other targeted therapies for the possible treatment of IgG4-RD, many of which already have FDA approval for treating other conditions. These therapies include:

IgG4-RD can affect any organ in the body and cause multi-organ disease. While corticosteroids, immunosuppressants, and targeted therapies can treat the underlying cause of immune dysfunction, some people may need organ-specific treatments.

Over time, inflammation and scarring due to IgG4-RD can lead to changes in an organ’s shape, structure, and function. These challenges may require individualized treatments such as organ-specific medications or surgery.

There is no definitive cure for IgG4-RD, but this condition is highly treatable. Most people notice symptom improvement within days to weeks of starting therapy.

While corticosteroids are the first-line treatment for IgG4-RD, a comprehensive plan may also include steroid-sparing immunosuppressants, targeted therapies, and organ-specific interventions.