Regina Berkovich, MD, PhD, provides insight on the considerations and patient awareness of the risk of infections with disease-modifying therapies in patients with multiple sclerosis.
Jeffrey Dunn, MD: The other potential issue with these medications is infections for the same reasons. If we're affecting the immune system there's an increased risk potentially of different infections either primary infections or opportunistic infections, is there a certain approach that you take? I know you probably always consider it and your risk benefit balance but how would you advise our colleagues to consider infections if they have a multiple sclerosis [MS] patient, they want to give the best therapy possible, they want to minimize relapse rate but they also want to minimize infection risk; what would be an approach, heed, advice or things to make sure that they would think of?
Regina Berkovich, MD, PhD: My advice would be looking into real numbers.
Jeffrey Dunn, MD: How do you mean?
Regina Berkovich, MD, PhD: I will tell you that recently we published (in) the International Journal of Multiple Sclerosis [International Journal of MS Care], the risk assessment that patients themselves assess their potentially risk of progressive multifocal leukoencephalopathy [PML] in the setting of natalizumab treatment. One of the most common answers (of) what they think their risk of PML might be was 50%.
Jeffrey Dunn, MD: Patients said this?
Regina Berkovich, MD, PhD: Yes.
Jeffrey Dunn, MD: That would be horrifying.
Regina Berkovich, MD, PhD: Exactly. And I have patients who are already on natalizumab, and they think their risk of PML might be about 30% and they still continue on it. You can only imagine what a relief for them to hear that it's actually always less than 1%. Looking into the facts is extremely important because assessment of the risk is a very emotional thing, that's what I've learned. I've been collecting this data on patients' risk assessment on PML since 2008 and I must say that I've learned a lot from looking at it. So it's been important to know the facts and stick to the facts. After that, yes, risk of infection is associated with every single disease-modifying therapy. You're right, but this is the equilibrium we have to maintain because we need to modulate or suppress the immune system but at the same time minimize the risk of infections, but this is where we should benefit majorly from (a) variety of disease-modifying therapies. Of course, in someone’s armamentarium if there are only 2 options out of 27, that's going to be impossible. That's why we need all 27. That's why we need 37; bring them on because the more medications are out there, the more maneuver we have. We can be more tactical, more strategical with different medications, with different risk rates and with different, let's say, incidence of lymphopenia or hypogammaglobulinemia. We can breach them, and we can switch. So I believe that we should no longer think about treatment with disease-modifying therapy (in terms of) you choose one and you stay on it. (The) reality is that rarely it happens this way anymore. We end up switching patients from one therapy to another and we should not feel bad about it. It's basically tailoring the immunomodulation or immunosuppression, depending on what we do, to the particular needs of these individuals for this particular period of life. Therefore, it would be, in my view, completely justifiable to switch patients to a different EMT prepregnancy and allow the patient to get pregnant while being on less risky disease- modifying therapy and perhaps then still switch to a different one whenever a different need occurs.
First of all, if someone shows evidence of routine infections you pay more attention to this person and you check the immunoglobulins level and if (the) patient has a low immunoglobulins level that's your marker.
Jeffrey Dunn, MD: Do you have a threshold for immunoglobulin level that concerns you?
Regina Berkovich, MD, PhD: Normal level?
Jeffrey Dunn, MD: A level where you might see an increased risk of infections.
Regina Berkovich, MD, PhD: If it's decreased, if it's outside of norm, if it's lower than normal, that's the red flag. Routine infections are the ones that are most common and associate with most of the MS symptoms and there are some immunologic theories saying that chronic infections such as chronic urinary tract infections [UTIs] may contribute to the higher risk of progression of the disease, which we still don't understand entirely.
Jeffrey Dunn, MD: If you identify a patient that you think might be more susceptible to infection, does the issue of reversibility come into play? Would that impact your choice of immunotherapy for that specific individual?
Regina Berkovich, MD, PhD: Possibly, yes, because whichever infection we are concerned about we would be more successful in preventing it if we have this agility to the plan.
Transcript Edited for Clarity