Question of the Week: Will the risk of PjP infections be higher or lower compared with prednisone of patients with IgG4-RD who are treated with B cell depletion?

The Short Answer

Thank you, Hua, for this follow-up. Understanding of an issue thoroughly usually requires another round or so of questions.

The answer to this one is that patients who are treated with B cell depletion, with or without a short course of prednisone at the start, are NOT generally at a high risk of an opportunistic infection such as PjP.

For this reason, we do not typically use antibiotic prophylaxis when aiming to induce remission in IgG4-RD with such a treatment regimen.

The Longer Answer and an Even More Important Additional Point

The key to preventing PjP and many other serious infections is likely the avoidance of long-term, high dose (e.g., 40-60 mg/day of prednisone for two months or longer). Prednisone courses of that duration and intensity are usually unnecessary in IgG4-RD. It’s the long-term, lower-dose use of steroids that is more likely to cause problems in IgG4-RD: osteoporosis, diabetes, cataracts, and so on.

There are, however, some important infectious issues to consider in the context of B cell depletion strategies. These stem primarily from issues related to: 1) viruses (hepatitis B, COVID, influenza); and 2) the vaccines that are used to prevent them.

Because our Fireside Chat this Thursday, August 22 is devoted entirely to this topic, I will address only one of these points here (see below). You can tune in later this week for more critical information on all of these topics from Dr. Camille Kotton, an infectious disease expert at the Massachusetts General Hospital. 

B Cell Depletion and Hepatitis B Reactivation

The important issue that I want to comment on here is the need to screen patients for hepatitis B infections before starting immunosuppressive therapy. Two BILLION people around the world have evidence of either past or current hepatitis B infection, and most don’t know it.

The reason for this is that the most common means of transmission of hepatitis B in many countries is at birth: from mother to child. Mother-to-child transmission may occur in utero, at the time of birth, or after birth. Most infections occur at the time of birth. An infected child may grow into adulthood and go through life without any evidence whatsoever of liver issues. However, if that child or adult needs to be treated with immunosuppression, latent hepatitis B can become “reactivated.”

Reactivation of hepatitis B can be very dangerous because it leads to liver failure in a high percentage of cases. The reason is that both high-dose steroids and B cell depletion can be associated with reactivation of hepatitis B.

BUT: this is completely preventable with routine pre-treatment testing.

Screening for latent hepatitis B is critical before starting treatment with an immunosuppressive agent. This guideline extends to immunosuppression of just about any kind but is it particularly important for both high-dose steroids and B cell depletion.

How is Screening Done?

Screening is simple. Two blood tests are performed:

• Hepatitis B surface antigen (HBsAg)

• Antibodies to hepatitis B core antigen (anti-HBc antibody)

The US Food and Drug Administration has issued boxed warnings for rituximab regarding an increased risk of hepatitis B reactivation among patients positive for HBsAg or anti-HBc.

If both of these tests are negative, then nothing further needs to be done and treatment can proceed.

A common scenario, however, is that a person is found to have anti-HBc antibodies and is completely unaware that he or she has latent hepatitis B. If this is the case, treatment can proceed but only after the patient has been started on an anti-viral medication to prevent hepatitis B reactivation.

If prophylactic treatment is needed, what medications are used?

There are two options – both pills taken once a day – that are very effective and extremely well-tolerated. These are:

• Tenofovir

• Entecavir

Treatment should be continued until patients are on low doses of prednisone or until (in the case of B cell depletion) the B cell numbers in the blood have returned to normal.

Conclusion

Benjamin Franklin, a printer, political thinker, politician, scientist, inventor, and diplomat, became famous for many things in the 1700s. One of these is the statement:

“An ounce of prevention is worth a pound of cure”.

Franklin penned this statement in a letter to his own newspaper, The Pennsylvania Gazette, following a visit to Boston in 1733 during which he became impressed by Boston’s fire prevention methods. Ben began his letter, entitled “On Protection of Towns from Fire,” with this famous expression. Nearly three centuries later, “An ounce of prevention is worth a pound of cure” applies equally well to the prevention of hepatitis B reactivation.

Looking forward to seeing you on the Fireside Chat with Dr. Kotton this Thursday. If you are unable to tune in live, you can review the discussion of all of the latest related to COVID, vaccinations, and other issues relevant to people living with IgG4-RD on the Resources page of our website one week afterwards.