Christen Kutz, PhD, PA-C

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

 

Infusion therapies. There are four infusion therapies available for MS treatment. Mitoxantrone, though not commonly used, is still available for relapsing and secondary progressive forms of MS. Common infections seen in clinical trials include upper respiratory, urinary tract, and sinus infections. A CBC, including platelets, should be obtained prior to each course of mitoxantrone and again if signs and symptoms of infection develop.¹⁰

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

 

Infusion therapies. There are four infusion therapies available for MS treatment. Mitoxantrone, though not commonly used, is still available for relapsing and secondary progressive forms of MS. Common infections seen in clinical trials include upper respiratory, urinary tract, and sinus infections. A CBC, including platelets, should be obtained prior to each course of mitoxantrone and again if signs and symptoms of infection develop.¹⁰

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

 

Infusion therapies. There are four infusion therapies available for MS treatment. Mitoxantrone, though not commonly used, is still available for relapsing and secondary progressive forms of MS. Common infections seen in clinical trials include upper respiratory, urinary tract, and sinus infections. A CBC, including platelets, should be obtained prior to each course of mitoxantrone and again if signs and symptoms of infection develop.¹⁰

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates