Is there a new treatment on the horizon for IgG4-related disease?

Jason Springer, MD, MS, an associate professor at Vanderbilt University Medical Center, talks with Rare Disease 360 about a landmark trial assessing a new treatment option for IgG4-related disease and the importance of communication among care teams involved in managing this patient population.

Question:

What are the signs and symptoms that present with IgG4-related disease? How can time to diagnosis be improved?

Jason Springer, MD, MS:

As far as the signs and symptoms, so it can affect multiple different organ systems. Go over some of the more common things, so it can involve the eyes, causing ritual orbital inflammation. This can lead to symptoms of double vision from pressure on the eye or potentially pain or swelling around the eye.

It can involve the glands, like the salivary glands, like the parotids and submandibular glands. They can get swollen. Potentially painful. It can also cause significant lymph adenopathy as well, persistent lymph adenopathy. It can present as a pancreatitis picture or it can involve the biliary tract, and so patients can have unexplained weight loss or jaundice or potentially abdominal pain.

Also, some of these patients will present with retroperitoneal inflammation, what we call retroperitoneal fibrosis. Some of those patients with retroperitoneal fibrosis will have IgG4-related disease. This can put pressure on important organs. A common area would be the ureter, where it can obstruct the ureter, causing backflow into the kidneys. Sometimes patients can have lower abdominal pain or back pain, but not always.

Then also, it can cause an inflammatory mass around the aorta, and causing inflammation to the aorta as well. This can lead to potentially narrowing of the aorta, and so symptoms of claudication in the legs, for instance. Some patients may have abdominal pain or lower back pain, not always.

Some less common things would include, it can cause inflammation of the thyroid, so a thyroiditis-type picture, or there can be inflammatory changes that occur in the lungs or potentially in the kidneys as well. Now, as far as improving the time to diagnosis, I think it’s like you mentioned, better recognition, awareness, so that providers can recognize the disease quicker and make the diagnosis. I think in the future, probably better diagnostic tests because right now we’re very dependent on biopsy. You can look at IgG4 levels in the blood, but they’re not always elevated. Hopefully in the future, we’ll have some improvements in our diagnostic tests.

Question:

Results of the phase 3 MITIGATE trial were recently published in The New England Journal of Medicine, detailing a potential new treatment option for IgG4-related disease. What was your take on the findings?

Jason Springer, MD, MS:

Yeah, the MITIGATE trial, I think it is a landmark trial for this disease, definitely. It was a randomized, controlled trial, so it could potentially lead to FDA approval of this drug. It looks specifically at this drug called inebilizumab, which is similar to rituximab. We use rituximab a lot in IgG4-related disease because we know it works really well. This drug targets B cells as well. But the difference is that the receptor is different, so this targets CD19, as opposed to rituximab, which targets the CD20 receptor. The importance of that is that the CD19 in the B-cell maturation tends to be on the B cells for longer, so much earlier compared to CD20, and also much later in their cycle. Potentially, it may have a more profound impact on B cells and potentially work better.

This was a multinational study, so it included not only sites in the US but sites in Europe and Asia as well. What they found is that when they used this drug compared to placebo, there were fewer relapses. Also, there were more patients by the end of the study that were in remission off of glucocorticoids, and less glucocorticoid use when using the drug.

As far as the adverse events, there were a higher number of infections in the group that got treated with this drug, which isn’t totally unexpected. We know this is an immunosuppressive drug. I wouldn’t say there was an excess number of infections. It’s probably what we’d expect with a medicine like this. I do think it is a landmark study, and I think it is exciting that we’re seeing a randomized, controlled trial in this disease. I think it opens up the door for future studies. I think it’s an exciting time for research in IgG4-related disease.

Question:

Can you talk about the importance of multidisciplinary care when it comes to managing patients with IgG4-related disease?

Jason Springer, MD, MS:

Yeah, I think in most cases, a multidisciplinary approach is important because it does affect different organs, and it is important to have a care team that includes the right specialists. It won’t always be the same for each patient. It depends what manifestations they have. The care team should always have somebody that is quarterback of the team that is managing everything and guiding the treatment. Typically, it’s a person that’s giving the systemic therapy, like the systemic immunosuppressive therapies. Then communication is very important. Sometimes this could be being in the same healthcare system, but if not, there just has to be very effective means of communication between the specialist.