Multiple Sclerosis: Safety Profiles of Disease-Modifying Therapies
The expansion of the multiple sclerosis (MS) treatment arsenal has led to more options for disease-modifying therapy (DMT) than ever before. Although the risk of side effects and the potential for complications vary by agent, these risks can generally be mitigated through careful patient selection, monitoring, and ongoing dialogue with patients.
How do you manage the risk of side effects and complications from DMTs?
Chief Emeritus, Division of Neurology
“I think that seeing patients frequently is among the best ways to approach the safety concerns of the newer DMTs.”
The paradigm right now really focuses on the prevention of damage, and we are not quite there yet with the repair of damage, which underscores the importance of patients being comfortable taking their DMT. Patient concerns regarding the safety of these treatments can be a barrier to adherence. Some patients may be highly risk averse, and for those patients who may be reluctant to take any DMT for their MS, sometimes it is possible to at least offer them a less efficacious drug that they will actually take because they have fewer concerns about side effects. The adverse-event profiles are real, and I certainly do not want to make a patient sick in order to make them better. One of the biggest concerns is urinary tract infections in patients with urinary retention. If the patient is prone to urinary tract infections, we are very careful about recommending some of the high-potency drugs.
I see most of my patients with MS every 3 months, and I like to get blood work at each visit. Fortunately, we can do this in the office. As some of the newer injectable drugs are now being self-administered at home, I think that seeing these patients more regularly may be especially important so that they do not end up getting lost in the system. Despite the best of intentions of clinicians with the use of electronic medical record systems, medication renewal may occur without the requisite monitoring. I think that seeing patients frequently is among the best ways to approach the safety concerns of the newer DMTs.
“Strategies are adapted to individual patient factors as well, including pregnancy. I have evolved to using the B-cell–depleting agents as a treatment of choice, particularly in patients with MS who require a bridge treatment between pregnancies.”
As our treatment monitoring requirements continue to evolve, we need to maintain an awareness of the potential risks associated with each of the DMTs that we use. One example is the potential for developing progressive multifocal leukoencephalopathy (PML), which is one of the most serious complications associated with agents such as natalizumab. We now recognize the importance of risk stratifying patients based on their JC virus serology, monitoring this status longitudinally to identify seroconversion, and adjusting our treatment approach accordingly. Another example of mitigating the risk of PML relates to monitoring for lymphopenia in dimethyl fumarate. Persistent lymphopenia is a characteristic factor in the rare cases of PML in dimethyl fumarate, so monitoring the patient closely and switching therapy when necessary are important.
Strategies are adapted to individual patient factors as well, including pregnancy. I have evolved to using the B-cell–depleting agents as a treatment of choice, particularly in patients with MS who require a bridge treatment between pregnancies. In the case of a female patient who had her first child and has plans for additional children, the B-cell–depleting therapies, such as ocrelizumab, are versatile in that you can potentially decide every 6 months whether to hold the treatment and try to become pregnant or receive another dose of medication. If the patient decides to, at some point, have another child, it offers a nice bridge of continued B-cell depletion after the medication is no longer circulating. Another favorable aspect of the B-cell monoclonal antibodies is that they do not cross the placenta in the first trimester, so this gives us an additional buffer of time.
“I think that it is important to talk with patients in a way that helps them to make an informed choice and to reassure them that the neurology team will monitor their safety.”
Every patient almost uniformly has questions about treatment side effects. I like to differentiate between side effects, which are experienced, and potential complications or risks. So, we have these conversations with our patients about safety in the context of efficacy, potential complications, and convenience. Because the number of treatment options has increased, these discussions tend to run long. From the neurologist’s perspective, one way to manage these discussions is to consider the mechanisms of action of the different medications.
The sphingosine-1-phosphate receptor modulators, for instance, have different safety profiles as compared with the anti-CD20 B-cell–depleting therapies. Patients may tend to think of that dichotomy as oral medications vs injectable medications, so I think that it is important to talk with patients in a way that helps them to make an informed choice and to reassure them that the neurology team will monitor their safety.
In terms of injectable B-cell therapies, I tell my patients about infusion reactions, and I inform them that they may experience sensations such as itchiness or scratchiness of the throat and/or a warm sensation through their body as part of their treatment. We give these individuals small doses of an antihistamine and a steroid before the treatment to help minimize these reactions. We then discuss the potential longer-term complications that we need to watch for, such as infections. While these patients may be at a somewhat increased risk of infection, they should not consider themselves to be immunosuppressed or avoid social contact because they are taking this medication. Finally, I tell my patients taking sphingosine-1-phosphate receptor modulators about the potential for headaches and increases in blood pressure.
It tends to be generally reassuring to patients that the safety profiles of many of these medications are quite favorable and that communication between the patient and neurologist, as well as checking blood tests, can help maximize safety.
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