Clyde E. Markowitz, MD

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.