Optimizing treatment for multiple sclerosis
“The presence of new relapse activity or ongoing new radiological activity apparent on MRI strongly suggests nonresponse to therapy and should trigger a change in treatment.”
—Sylvia Klineova, MD
Living with multiple sclerosis (MS) takes a toll on patients and their families. The disease’s physical and neurological effects can impact everything from mobility, speech, vision and cognition to bowel and bladder function.1 Too often, these effects impede ability to perform routine activities, force patients into isolation and leave many people struggling with anxiety and depression.1-4
Fortunately, recent medical advances have improved disease management, giving patients more hope than ever for reducing relapses, stalling neurologic and functional decline and potentially delaying progression to secondary-progressive MS.1
Newer therapies offer tailored treatment
The field of MS therapeutics has expanded dramatically since the first medication was introduced almost 30 years ago, says Sylvia Klineova, MD, Assistant Professor of Neurology, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai in New York City. “We currently have more than 20 medications, including generic formulations, that can be used to treat our patients. While that number might seem overwhelming to patients and physicians when deciding on a treatment plan, this magnitude of agents allows us to tailor the treatment more to the individual needs and preferences of our patients,” Dr. Klineova says. “Since MS is largely an unpredictable disease and patients vary in their disease course and response to the treatment, having more options with different mechanisms of action gives patients a higher chance to find the medication that works.”
This also makes it easier to find a treatment that’s not associated with the drawbacks of certain older disease-modifying therapies (DMTs), such as lower efficacy and regular testing for signs of rare but serious adverse effects. “Some of the agents now available are evolved versions of their predecessors with better side-effect profiles and less strenuous monitoring, thus making them easier to manage by patients,” says Dr. Klineova
Why early intervention is crucial
Degeneration of white and gray matter due to loss of myelin and, ultimately, death of neurons typical in MS begin well before diagnosis, possibly during childhood.5 That lost brain volume cannot be recovered, as no current therapy can repair the myelin sheath and restore lost function. “To offer the best prognosis for our patients, clinicians need to achieve early MS diagnosis and early treatment in the disease course with the preventive agents that we have,” stresses Dr. Klineova.
For patients who present with an initial demyelinating event consistent with clinically isolated syndrome (CIS), start a DMT if the accompanying prognostic factors (e.g., presence of additional demyelinating lesions in the brain and spinal cord, presence of oligoclonal bands in the cerebrospinal fluid) suggest increased risk of a second relapse. The American Academy of Neurology (AAN) supports prescribing a DMT after a single clinical demyelinating event with two or more brain or spinal cord lesions6 —although you may want to consider starting a DMT even if only one brain or spinal cord lesion is present, says Barbara Green, MD, of the MS Center for Innovations in Care, Missouri Baptist Hospital in St. Louis.
In addition, offer a DMT to a patient with diagnosed relapsing-remitting MS (RRMS) after an acute exacerbation (or relapse) or if MRI shows new activity, per AAN guidelines.6 If a patient presents with an episode potentially suggestive of MS onset (such as optic neuritis) but has a normal brain scan and lumbar puncture, delay DMT therapy but schedule a follow-up MRI in 3 months to check for disease activity, Dr. Green suggests.
Strategies for treating relapsing forms of MS
The first step in matching the right medication to the right patient: Having an open dialogue at each visit. “Interfacing with patients regularly is important,” says Dr. Green. “These discussions are key to determining disease activity and whether or when a change in treatment is needed.” Here are factors to consider before and during treatment.
Choosing a disease-modifying therapy
Although clinical guidelines dictate when to start and switch treatment, deciding on the most appropriate initial therapy is still an open question. “We do not have a clear-cut algorithm,” Dr. Green says. “We have many choices and decision trees but no firm data on which DMTs are best for specific patients.” When weighing the options, experts suggest the following:
Schedule a separate visit.
With so many options available, this can make the discussion about DMT initiation easier.6 Start the conversation by setting clear clinical and functional treatment goals, then explain medication risks and benefits based on clinical evidence. Also review the patient’s record for susceptibility to adverse events with specific DMTs.
Ask them to be candid about their life situation—
including topics such as work or school schedule, pregnancy planning, access to treatment via commercial health insurance or Medicare—and gauge the patient’s preference based on lifestyle. For example, those who travel frequently may prefer an infused DMT so they don’t have to remember to pack their medication.
Consider age and stage of life.
“A younger patient may not want to deal with medication side effects that will impinge on their lifestyle,” Dr. Green says. “But that patient has many years ahead and wants to stop neuron loss in its tracks to ensure a higher quality of life throughout the lifespan.
Weigh higher efficacy vs. lower toxicity.
A major consideration is whether to start with a DMT with a lower-efficacy/higher-safety profile and switch to a higher-efficacy DMT if new MS activity develops, or start with a stronger, higher-efficacy/lower-safety agent first. While patient lifestyle and preferences should be considered, Drs. Green and Klineova suggest prescribing a lower efficacy/higher safety DMT in a patient with less aggressive disease.
By contrast, several clinical and imaging factors—such as male sex, older age at disease onset, high lesion load in the brain and spinal cord at diagnosis, multiple relapses with short time between relapses, initial motor and cerebellar signs, and incomplete recovery from relapses—can signal high disease activity and increased risk of early progression. “Finding these prognostic factors in any patient would provide a valid case for prescribing a high-efficacy medication first-line,” Dr. Klineova says.
Factor in comorbidities.
Those caused by or affecting patients with MS—such as depression, sleep disorders, hypertension, hyperlipidemia, chronic lung disease and gastrointestinal disease, among others—can worsen the prognosis.7-9 “Comorbidities can have a direct negative impact on brain health and neurological reserve, such as presence of vascular risk factors with resultant stroke,” says Dr. Klineova, so work closely with the patient’s primary care provider and subspecialists to ensure comorbidities are being managed.
It's also key to consider comorbidities when choosing a DMT. For example, avoid agents with more severe GI effects, such as dimethyl fumarate and teriflunomide, in patients with GI disease. In patients with depression, avoid interferons, which can worsen the mood disorder. And choose a low-toxicity DMT for older patients, who have more comorbidities and are vulnerable to medication effects, Dr. Green says.
Monitoring treatment response
After a patient starts a new medication, experts recommend following up with these strategies:
Schedule office visits every 3 months—
or sooner if the patient shows signs of physical/cognitive decline or experiences medication-related complications, Dr. Klineova says. Regular radiologic surveillance should include a brain MRI annually. Sometimes, a cervical spine MRI is also done, which providers can decide how often to do based on the situation.
Keep patients involved.
Instruct patients to monitor their disease activity and report any new neurological symptom that lasts at least 24 hours and is not caused by fever or infection. Document any reported symptoms that could suggest new disease activity.
Encourage them to talk about any concerns.
Build time for clinician-patient discussion into each visit, and urge patients to openly discuss how their MS is affecting their life. Many patients sense losses in function that diminish quality of life and that may signal worsening MS, but they either don’t attribute the symptoms to MS or they’re too embarrassed to discuss them, Dr. Green notes. For example, many patients are reluctant to bring up sexual dysfunction, poor performance at work, problems with bladder or bowel control or suspected cognitive changes. These signs of MS progression need to be teased out. “Some patients don’t tell you everything, so you have to ask questions at every visit,” Dr. Green says.
Managing acute exacerbations
An acute exacerbation, which can occur at any point in treatment, signals ongoing disease activity and can eventually lead to MS progression.10 When a patient presents with possible symptoms of an exacerbation—such as loss of vision, strength or sensation, or lack of balance accompanied by fatigue—consider the following:
Explore possible culprits.
Determine during the patient interview and examination if the symptoms have another cause, such as infection or medication reaction, Dr. Green says. If no alternative cause is apparent, immediately start treating the exacerbation and order an MRI to check for new disease activity.
Treat according to symptom severity.
If the exacerbation is mild or moderate and marked by a specific symptom such as pain or fatigue, target the symptom with an OTC nonsteroidal anti-inflammatory drug (NSAID) or a review of sleep hygiene, Dr. Green suggests. If poor muscle tone is predominant, refer the patient for occupational or physical therapy. For more severe exacerbations, anti-inflammatory corticosteroids can lessen the attack’s severity and duration. Be prepared to manage corticosteroid-related adverse effects if they occur, such as by prescribing an OTC agent to counter GI distress or insomnia.
Consider switching DMTs.
See the patient 1 month after starting acute therapy to review the MRI findings and determine whether a change in treatment is needed. (For more guidance, see the box below)
How to spot progression to SPMS
Transition from RRMS to secondary-progressive MS (SPMS) is characterized by worsening of disability independent of clinical relapses for more than 6 months. However, Dr. Klineova says, applying this rule to clinical practice can be challenging.11 While no objective biological or imaging marker definitively signals transition to progressive MS, certain signs found during the office visit should raise a red flag for patients without a recent exacerbation or new MRI activity, Dr. Green says. These include:
- Increased dependence on a walker or other assistive device
- Worsening scores on the Multiple Sclerosis Quality of Life Inventory (MSQLI), Expanded Disability Status Scale (EDSS) or similar assessments
- Increased difficulty with the Timed 25-Foot Walk Test
- Declining work performance
Fortunately, several DMTs have shown efficacy in treating this advanced stage of MS and are now FDA-approved to treat active SPMS, Dr. Klineova notes. Change to an appropriate DMT as soon as progression to SPMS is suspected, and continue to work with the patient to gauge preference and ability to follow the prescription. Continue with visits every 3 months and perform in-office clinical measures, such as neurological exams and standardized walking tests, along with MRI to measure disease progression.
—by Pete Kelly
Illustration by Matt Chinworth
Illustration by Matt Chinworth
When to switch therapies
Many patients will experience breakthrough disease activity that necessitates a change to a different DMT, either with higher efficacy or a different mechanism of action.6 Yet the definition of treatment response is not a clear one, says Sylvia Klineova, MD, MS, Assistant Professor of Neurology, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai in New York City. “However, we can agree that the presence of new relapse activity or ongoing new radiological activity apparent on MRI strongly suggests nonresponse to therapy and should trigger a change in treatment.” In general, a switch may be needed if:
- Function has declined over the past 6 months, regardless of whether exacerbations occurred
- The patient suffers clinical exacerbations despite treatment adherence
- The latest MRI shows more or larger lesions
- Quality of life is diminished, even though the patient has received the DMT over a reasonable period
While assessments such as the Multiple Sclerosis Quality of Life Inventory and Expanded Disability Status Scale help measure physical and cognitive function and quality of life during treatment, clear signs of disease progression may also be detected during patient visits, Dr. Klineova says. For example:
- Does the patient appear weaker?
- Have they started using a cane or walker?
- Have they recently fallen at home?
- Is the patient having trouble with stairs?
- Is the patient afraid to bathe or shower (because of difficulty entering and exiting the bathtub)?
- Are they unable to complete household chores?
- Are they leaving the house less often (because of gait difficulty)?
Other factors, such as adverse events and medication nonadherence, also can diminish first-line DMT effectiveness and necessitate a second-line trial. As with selecting the initial agent, the patient’s preferences, lifestyle, comorbidities and susceptibility to adverse effects need to be considered.
“Interfacing with patients regularly is
important. These discussions are key to
determining disease activity.”
—Sylvia Klineova, MD
References
1. National Multiple Sclerosis Society. Multiple Sclerosis: Just the Facts. Available at nationalmssociety.org.
2. Hakim EA, et al. The social impact of multiple sclerosis—a study of 305 patients and their relatives. Disabil Rehabil. 2000;22(6):288-293.
3. National Multiple Sclerosis Society. Depression. Available at nationalmssociety.org.
4. Owens GM. Economic burden of multiple sclerosis and the role of managed care organizations in multiple sclerosis management. Am J Manag Care. 2016;22:S151-S158.
5. Cerqueira JJ. Time matters in multiple sclerosis: Can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J Neurol Neurosurg Psychiatry. 2018;89:844-850.
6. Rae-Grant A, et al. Practice guideline: disease-modifying therapies for adults with multiple sclerosis. Report of the American Academy of Neurology. Published April 2018. Available at aan.com.
7. Edwards NC, et al. Comorbidity in US patients with multiple sclerosis. Patient Relat Outcome Meas. 2018;9:97-102.
8. Marrie RA. Comorbidity in multiple sclerosis: some answers, more questions. Int J MS Care. 2016;18(6):271-272.
9. Gupta S, et al. Osteoporosis and multiple sclerosis: risk factors, pathophysiology, and therapeutic interventions. CNS Drugs. 2014;28(8):731-742.
10. National Multiple Sclerosis Society. Managing relapses. Available at nationalmssociety.org.
11. Katz-Sand I, et al. Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis. Mult Scler. 2014;20(12):1654-1657.
Practice Pearls:
Encouraging lifestyle changes to help patients manage MS
Study findings published in Neurology revealed that between 850,000 and 913,000 people are living with multiple sclerosis (MS) in the United States—a figure that eclipses the 400,000 prevalence figure that had been previously estimated, with women making up 75% of the total.1 While disease-modifying medication is crucial to slowing progression of the disease, physicians are increasingly using nondrug strategies as well to help patients manage their symptoms.
“There has been a lot of research put into medications, and they’ve come a long way,” says Jennifer Hofmann, physician assistant and Clinical Associate Professor at Pace University’s College of Health Professions in Pleasantville, NY. “But they don’t address cognitive issues, depression, heat intolerance and fatigue—the quality-of-life issues that affect patients day to day.”
An expanding body of research points to the importance of lifestyle factors such as diet, exercise and stress management in easing physical symptoms and psychological distress in patients with MS.2 Hofmann and Jacqueline Nicholas, MD, System Chief of Neuroimmunology & Multiple Sclerosis at the OhioHealth MS Center in Columbus, offer these suggestions for promoting lifestyle changes and improving quality of life.
Ask the right questions.
Many patients, when asked how they’re doing, will say “I’m fine,” Dr. Nicholas says. So she and Hofmann will ask questions designed to bring up problems patients may otherwise gloss over or not want to complain about: “What are the primary symptoms on a day-to-day basis that are bothering you? Do you notice any fluctuations in your symptoms depending on what you’re doing or eating? How is your energy level? How are you sleeping?”
And then they listen. “There’s a lot of pressure to get to the point and get patients in and out, but that’s hard to do with MS because it’s so multifactorial. Asking questions and listening carefully to the answers can help you focus on patients’ needs to make the most of each visit,” Hofmann says.
Treat the patient as a partner.
Instead of dictating what the patient should do, Hofmann shares research about lifestyle factors and phrases it carefully—“Did you know about this?” rather than “You should be doing this.” In addition, Dr. Nicholas advises probing further, for example: “ ‘You just told me you’re fatigued. So let’s talk about that.’ When they realize I’m not being critical of them but rather that I’m trying to enhance their life based on research, it helps,” Dr. Nicholas says. “The majority of patients are amazing people who want to do everything they can so they can function well into their later years and enjoy their grandchildren.” She tells them she wants to share everything she knows that can make that possible.
Advocate a heart-healthy diet.
Although there is no specific diet that has been found to slow the progression of MS, experts recommend the low-fat, high-fiber diet outlined by the American Heart Association. This eating plan centers on fruits and vegetables, whole grains, lean meats such as chicken and turkey, fish high in omega-3 fatty acids such as salmon, as well as beans, lentils and nuts. Another reason to recommend a heart-healthy diet: It helps ward off comorbidities, such as cardiovascular disease, that can make MS worse, says Dr. Nicholas. Also advise patients to avoid highly processed foods; an unhealthy diet is associated with the accrual of MS lesions.3
Recommend vitamin D.
Numerous studies have associated MS progression with low vitamin D levels. “Vitamin D, especially D3, regulates many different processes in the body, including myelination of cells,” Hofmann says. She will check MS patients’ blood levels and recommend a D3 supplement if they’re deficient. The dosage may be 2,000 to 5,000 IUs per day, depending on the patient.4
Consider other supplements.
One is an omega-3 fish oil supplement. “Omega-3s are building blocks for the myelin sheath,” Hofmann says. “It’s like insulation around electrical wires.” Ideally, patients would get enough through foods (like salmon), but many don’t. If that’s the case, Hofmann will recommend 2 grams of fish oil a day. For those who don’t tolerate it well, she suggests burpless forms. Vegetarians can take flaxseed oil.
Coenzyme Q10, an antioxidant produced naturally by the body, is another consideration and “has the most support in terms of clinical data,” says Hofmann. “Depression and fatigue can be improved when you take it.” Her typical suggested dosage is 500 mg a day. She says it’s important to note that coenzyme Q10 is associated with possible drug interactions; for example, it may lower blood pressure and have an additive effect with BP-lowering meds and may reduce the effectiveness of coumadin. However, she adds: “The recommendation is to be cautious but not necessarily withhold it.”
Therefore, she urges healthcare professionals to ask their patients at each visit to list every drug and supplement they’re taking. All may pose a risk of drug interactions, she says. “Often people think supplements won’t interact, but that’s not true. So they need to feel comfortable telling you everything they’re taking, whether prescribed or OTC.”
Be an exercise advocate.
“Fatigue is the most common experience of MS patients,” Dr. Nicholas says. “Extensive research shows the importance of exercise in helping to improve energy. It also helps improve cognition and prevent the development of other comorbidities that make MS worse,” such as diabetes and cardiovascular disease.
She recommends that every patient participate in some form of aerobic exercise—and she advises to start out small. “If I tell someone with MS who has extreme fatigue to exercise, that can be a daunting task. Instead, I’ll say, ‘Let’s find 5 to 10 minutes three times a week to work in more movement.’ ” That could be riding an exercise bike, taking a walk or doing an exercise video, including online. “There are all kinds of videos out there for people with MS,” she says. For example, the Cleveland Clinic has a YouTube video of exercises for people with MS.
Suggest yoga.
“Even if done moderately, yoga builds strength in the core and helps with balance,” Hofmann says. It’s also something that can be modified: “It can be done sitting in a chair, standing up or lying down,” she says. “It incorporates not just movement but breathing and mindfulness, which is important because depression is more common in patients who have MS.”
Point patients to aquatic therapy.
Many communities have a pool that offers classes in water aerobics. “Working out in water helps with stretching tight muscles,” Hofmann says. “You have more fluid movement when you’re in the water, and the workout is nonimpact.” One caution: The temperature should not exceed 84 degrees Fahrenheit. “Excessive heat can make MS symptoms worse,” says Hofmann.
Encourage them to build a support system.
Most people don’t want to admit they need help or that they can’t do something, Dr. Nicholas says. But identifying people in their lives who they can go to for help can make a huge difference to people with MS. “Maybe it’s the busy mom saying, ‘I’m really fatigued today. I’m going to ask if my friend can take my kids after school so I can get some rest,’” Dr. Nicholas says. “A lot of patients are trying to be superheroes dealing with this neurological disease, and when they realize it’s okay to ask for help and that there are others out there who want to help, they can be more successful.”
Brainstorm ways to reduce stress.
There may be family members or friends who increase patients’ stress, or it may be a coworker or job. Dr. Nicholas discusses this with her patients and asks whether there are ways to minimize contact with problematic people. If the job is the problem, she asks whether working from home is possible. “Given the amount of energy it takes for them to get into the office and then function in a loud and stressful environment, they can often be more successful in that job if they work remotely,” she says. “I have patients who are nurses who have gone into case management and do their work over the phone from home.”
Boost their social connections.
“If patients are restricted to their home and can’t get out as much, that can harm their cognition,” says Dr. Nicholas. “Being present and listening to stories is an important cognitive task.” So if someone is isolated, she assesses their circumstances and recommends how patients can be more involved with family, friends, religious organizations or the community.
Refer patients to online support.
“The National Multiple Sclerosis Society is a tremendous resource for patients, providers and families,” Hofmann says. “It’s really excellent and easy to follow and has up-to-date information.” She refers her patients to nationalmssociety.org. Another helpful organization is the Multiple Sclerosis Association of America at mymsaa.org.
—by Andrea Barbalich
References
1. Wallin MT, et al. The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology. 2019; 92(10).
2. Marck CH, et al. Health outcomes and adherence to a healthy lifestyle after intervention in people with multiple sclerosis: Three-year follow-up. PLoS One. 2018; 13(5):e0197759.
3. Jakimovski D, et al. Dietary and lifestyle factors in multiple sclerosis progression: results from a 5-year longitudinal MRI study. J Neurol. 2019;266(4):866-875.
4. Hempel S, et al. A systematic review of modifiable risk factors in the progression of multiple sclerosis. Mult Scler. 2017;23(4):525-533.
Improving adherence
to disease-modifying therapies
“Patients who consider
themselves fully
informed will more
likely be adherent.”
—Barbara Green, MD
Unfortunately, research shows that many people with multiple sclerosis (MS) discontinue their disease-modifying therapy (DMT). As many as 4 in 10 patients discontinue their injectable DMTs, and 3 in 10 stop following their oral DMT regimen within 5 years of their MS diagnosis. Certain issues that typically impede adherence to prescription medications—such as fear of side effects, cost and inconvenient dosing—also occur with DMTs. These obstacles, however, are compounded by challenges specific to patients with MS, such as cognitive deficits, depression and lost physical function. Not surprisingly, nonadherence to DMTs is significantly associated with an increased risk of relapse, hospitalization and emergency visits.1-3
The good news: Patients often become motivated to follow their treatment plan once they understand that MS, while incurable, can be controlled. “Patients who consider themselves fully informed will more likely be adherent,” says Barbara Green, MD, of the MS Center for Innovations in Care, Missouri Baptist Hospital in St. Louis.
The key is to get patients on board from the start by setting clear treatment goals, explaining how a DMT works and why you’re prescribing it, and establishing a strong clinician-patient relationship that continues with each visit. The following strategies can help ensure your patients stay on track with their treatment plan.
Put side effects into perspective
DMTs can potentially cause distressing effects such as nausea, vomiting, diarrhea and hair loss, which is why some patients are hesitant to start a DMT in the first place: “Many patients will read an agent’s prescribing information and expect every single side effect that is listed,” says Sylvia Klineova, MD, Assistant Professor of Neurology at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai in New York City. “You can curb the patient’s anxiety before starting treatment by discussing the potential effects and how they are recorded in the research trials, and by listing the most common adverse effects observed with a particular medication.”
Also be prepared to steer patients through transient but troublesome side effects. For example, prescribe an OTC antidiarrheal or antinausea medication to counter DMT-related GI problems, Dr. Green suggests. If side effects are still intolerable, consider changing to another DMT class. For patients who report hair loss, explain that it’s often temporary and their hair will regrow in time.4 However, keep in mind that other medications, such as antidepressants, as well as hormonal changes and stress can also cause hair loss; therefore, some investigation may be warranted.
Help them weigh risks vs. benefits
Regularly share new and existing data with patients on DMT risk, and keep them abreast of your plan for preventing serious complications. For example, natalizumab can cause progressive multifocal leukoencephalopathy (PML) in patients with the human polyomavirus (or JC virus).5 However, regularly testing patients for JC virus antibodies and for low lymphocyte counts can detect the increased risk and prompt a discussion about changing treatments. Dr. Green notes that some patients choose to continue taking a DMT despite certain risks because they realize the agent is controlling their MS. This underscores the value of ongoing patient-clinician communication throughout treatment.
Emphasize the need for realistic expectations
Too often, Dr. Klineova says, patients get frustrated and stop taking a DMT because it didn’t resolve their prior residual symptoms. Many patients, especially those newly diagnosed with MS, don’t realize that DMTs are not formulated to alleviate all existing symptoms or restore function. So it’s crucial to discuss expectations and treatment goals at the outset, clearly explain what a DMT can and cannot do and manage coexisting symptoms throughout treatment to keep patients engaged.
Stress the importance of ongoing therapy
Some patients whose MS remains stable for years might stop taking their DMT, thinking their disease is in remission and no longer requires treatment. “Explain to patients that even when they don’t feel new clinical symptoms, the ongoing disease can still cause new brain or spinal cord lesions, making it important to continue DMT treatment,” Dr. Klineova says.
Ask about injection fatigue
Research shows that adherence to injectable DMTs may be incomplete, and injection-related pain or discomfort can affect patients who have been using long-term self-administered injectable therapies.6 To help them overcome injection fatigue, make sure they are following proper technique. “I usually refer patients for training, even those who have been injecting long-term, to ensure that the depth of the needle is appropriate, injection location is correct, and that they are changing locations frequently enough,” says Dr. Klineova, adding that pharmaceutical companies also provide nursing support and patient training. Another tip: Advise patients to prep injection sites with soap and water to avoid burning from alcohol, and to allow the medication to reach room temperature before injecting.
Check for cognitive deficits
Cognitive impairment is a common sequela of MS, and the ensuing confusion, memory loss and impaired judgment can impede DMT adherence.7,8 If you suspect problems based on patient interviews and in-office testing, consider alternative methods of managing medication schedules and dosing, Dr. Klineova says. Suggest use of pill boxes, alarms or smartphone apps to stay on top of dosing, and show family members how to prepare and track medication. Alternatively, a visiting nurse service or home health aide may be necessary for some patients.
“Depression requires
the same level of
attention as MS.
You need to get the
depression under
control before you can
treat the MS.”
—Barbara Green, MD
Screen for depression
Chronic depression, which affects nearly 1 in 4 patients with MS, can derail treatment adherence.9 Aside from diminishing patients’ motivation to manage their disease, depression also can worsen cognitive function.10 “Depression requires the same level of attention as MS,” Dr. Green says. “You need to get the depression under control before you can treat the MS.”
Recognizing depressive symptoms early can help keep patients on track, Dr. Klineova adds. Encourage patients at each visit to openly discuss their feelings of sadness or anxiety related to their MS. Patients who don’t appear to be depressed may be confronting other potentially disruptive personal issues that surface during these discussions, such as complicated family problems or overall anger about having the disease. Ask patients up front if they’re regularly taking their medication and refer to a psychiatrist or psychotherapist if you suspect the patient is struggling with their mental health.
Address financial issues
Most patients cannot start a DMT without a third-party payer or financial assistance.11 Additionally, some lose prior authorization for a DMT, either because their plan stops covering the medication or their employer changes insurance plans. Still other patients try to cut corners by taking their DMTs in lower doses or less frequently than prescribed, Dr. Green adds. Therefore, be sure to ask about their access to medication. If needed, refer them to patient-assistance programs offered by pharmaceutical companies or nonprofits such as the Patient Advocate Foundation (patientadvocate.org). For a list of financial resources, visit https://mymsaa.org/ms-information/prescription-assistance.
Maintain an open dialogue
Rather than try to identify an agent, some physicians may opt to give patients a list of DMTs, then advise them to research online and choose one. By leaving this decision to the patient, Dr. Green says, providers are sacrificing the clinician-patient alliance integral to effective MS disease management—and opening the door to a potentially suboptimal therapy and poor adherence. “I don’t support either pushing a medication on a patient or them completely taking control of the decision-making process,” Dr. Klineova adds. “Choosing a DMT is always a joint decision between physician and patient.”
—by Pete Kelly
References
1. National Multiple Sclerosis Society. Disease-modifying therapies for MS. Available at nationalmssociety.org.
2. Burks J, et al. Adherence to disease-modifying therapies and its impact on relapse, health resource utilization, and costs among patients with multiple sclerosis. Clinicoecon Outcomes Res. 2017;9:251-260.
3. Kleinsinger F. The unmet challenge of medication nonadherence. Perm J. 2018;22:18-033.
4. MS treatment and hair loss: what you need to know. Available at overcomingms.org.
5. Yukitake M. Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis: a comprehensive review. Clin Exp Neuroimmunol. 2018;9(suppl 1):37-47.
6. Devonshire V, et al. The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18:69-77.
7. Jongen PJ, et al. Cognitive impairment in multiple sclerosis. Minerva Med. 2012;103(2):73-96.
8. Verdugo RM, et al. Adherence to disease-modifying treatments in patients with multiple sclerosis in Spain. Patient Prefer Adherence. 2019;13:261-272.
9. Marrie RA, et al. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015;21(3):305-317.
10. Perini G, et al. Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatr Dis Treat. 2019;15:1249-1258.
11. Wang G, et al. Health insurance affects the use of disease-modifying therapy in multiple sclerosis. Neurology. 2016;87(4):365-374.
Case Studies
PATIENT: CLAIRE, A 37-YEAR-OLD SCHOOLTEACHER, HAD A RIGHT OPTIC NEURITIS EPISODE 2 YEARS AGO. SHE DID NOT SEEK TREATMENT AT THAT TIME.
“Claire liked the convenience of
self-injection”
PHYSICIAN:
Fred D. Lublin, MD, Saunders Family Professor of Neurology and Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai Medical Center
History:
Claire presented to our MS Center after encountering dizziness, unsteady gait and vision problems over 2 days. Upon presentation, she had double vision and left facial numbness. Examination revealed an internuclear ophthalmoplegia, which was evident on gaze to the right. She also had decreased color vision in her right eye and vertigo. Finger-to-nose testing showed bilateral dysmetria. She had full strength in her extremities, but her gait was ataxic and she could not perform tandem walking. She was treated acutely with high-dose oral steroids for symptom relief.
A subsequent brain MRI showed multiple periventricular lesions and a gadolinium-enhanced lesion in the left pons. Lumbar puncture revealed a white blood cell count of 8/mL, cerebrospinal fluid total protein of 64 mg/dL, and 5 unique oligoclonal bands. Standard labs were all normal, but she was JC antibody–positive. Based on these findings, we diagnosed relapsing-remitting multiple sclerosis with recent activity.
Claire’s dizziness and unsteady gait were interfering with her teaching job, and she had missed 4 days at school over the past week. Of note, Claire, a mother of two girls, was not planning to have any more children.
Initiating treatment:
We discussed Claire’s treatment options. She was given the choice of an anti-CD20 monoclonal antibody given as a once-monthly self-injection or the same class of agent administered intravenously every 6 months. Claire liked the convenience of a monthly self-administered injection. Before starting the agent, we discussed the risk of infection with an anti-CD20 antibody and urged Claire to report any unusual symptoms. She also was advised to get all necessary immunizations before starting treatment, as anti-CD20 antibodies may diminish vaccine effectiveness.
Upon follow-up 1 year later, Claire had not experienced another attack, and MRI findings were stable. Her balance was improved, and she had not missed any days at her teaching job, although she still had difficulty with tandem walking.
Considerations:
Many disease-modifying therapies (DMTs) are available for relapsing MS. There are also two main approaches to treatment: Either choose a high-efficacy drug such as an anti-CD20 antibody in the first line, or start with a moderate-efficacy agent and intensify treatment later as needed. No clear data exist to guide us toward either approach, so initiating treatment comes down to a discussion between patient and clinician.
Claire’s lesion load in the brain stem caused severe impairment and could portend a worse prognosis, so initial treatment needed to be aggressive. Anti-CD20 B-cell therapies have shown effectiveness in relapsing forms of MS, so the expectation was that this class of agent would provide excellent disease control. Another high-efficacy agent, natalizumab, was not offered to Claire as she was JC antibody–positive and, thus, at risk for progressive multifocal leukoencephalopathy.
Three anti-CD20 antibodies are indicated for relapsing MS. Two are infused every 6 months, the other is injected subcutaneously once monthly. These agents are formulated to enable patients to live as normally as possible during treatment. When discussing therapy with patients, it’s imperative to ask about family planning, as this could influence their choice. In Claire’s case, once-monthly self-injection was more convenient. On the other hand, if a woman wants to start a family, an infused agent would allow her to attempt conception between infusions while delivering the disease protection she would need during the early phases of pregnancy.
The earlier we treat patients with MS with any available therapy, the better they do. Consider a high-efficacy DMT such as an anti-CD20 antibody early in the disease course, but do so in the context of shared decision-making with the patient. Risk assessment, safety assessment, the potential for family planning, monitoring requirements, insurance issues and preferences toward route and frequency of administration all need to be addressed when planning therapy.
KOL on Demand
PATIENT: ROB, 40, HAD A 6-YEAR HISTORY OF MS AND WAS ON AN INJECTABLE DMT WHEN HE SUFFERED A RELAPSE.
“Rob was happy to switch to another therapy”
PHYSICIAN:
Fred D. Lublin, MD
Treatment history:
Rob, a TV producer, showed signs of MS activity 10 years ago, although he was not diagnosed until 7 years ago. His symptoms started at age 30, when Rob developed left optic neuritis, which improved partially with a course of IV steroids. His neurological exam at that time was normal except for decreased color vision in the left eye. His past medical history and family history were unremarkable, and an MRI scan of the brain revealed one juxtacortical lesion but otherwise was normal. At that time, he did not meet the diagnostic criteria for MS, and his symptoms were attributed to clinically isolated syndrome (CIS)-optic neuritis.
I first saw Rob after his second attack at age 33, when he developed a partial myelitis with residual numbness in his feet and decreased balance. MRI scan of the brain revealed three periventricular lesions; MRI scan of the C spine showed a lesion at C2. Based on these findings, I diagnosed Rob with MS and started him on interferon beta-1b given by subcutaneous injection three times weekly. Rob had no further attacks for 3 years; however, at age 36, he developed horizontal diplopia and right facial numbness, which improved with a course of IV steroids. An MRI scan of the brain revealed a new lesion in the right pons, which enhanced with gadolinium, indicating inflammatory activity.
Initiating treatment:
Though Rob had responded well to IV steroids, I suggested he would benefit by switching to a more efficacious agent to reduce the risk of future attacks, specifically an oral S1P modulator. Rob liked the idea of taking a pill instead of having weekly injections. He underwent the usual premedication workup for S1P modulators to check for contraindications: ophthalmologic examination, cardiogram and skin examination, all of which were normal.
Rob has been on an S1P modulator for approximately 5 years now. He has had no MS attacks in that time, and his MRI scans have remained stable. His
absolute lymphocyte counts have been around 800, which is expected on this type of therapy. He has been able to continue working as a TV producer and is very happy with his medication regimen.
Considerations:
The main reason I recommended that Rob switch to an S1P modulator was his breakthrough activity on interferon, as this therapeutic class has been shown to have higher efficacy in patients like Rob who develop new MS activity. This is, of course, always a joint decision made by both the patient and physician. I provide the patient with the information to make a decision and, together, we decide what will work best. In Rob’s case, this has proved successful. His case also shows how patients may find one medication regimen burdensome and welcome the
opportunity to switch to another medication.
Q&A
Insight on managing multiple sclerosis
Taking a team approach
Q: Why is an interdisciplinary approach key for managing multiple sclerosis (MS)?
A: If MS were simple, a neurologist would be sufficient, but MS impacts multiple systems throughout the central nervous system. Commonly affected are cognition, gait, mood and often relationships, particularly over time. One person may not be sufficient to deal with all those issues, as in the phrase, “It takes a village.”
Who are the right people for that village? The answer depends on where you are in the course of MS. It may include a physiatrist, occupational therapist, physical therapist, speech therapist, neuropsychologist, urologist and, one component I have found really central and often missing, the nurse navigator. In fact in our practice, the most crucial member is the nurse navigator, a professional who serves as educator, makes sure other members of the team are connected and gets people through other issues such as insurance or dealing with medications. Maybe the last team member is the social worker, who can be found through your own practice or through the MS Society. This person can be very helpful dealing with the social impact of MS.
—Barry A. Hendin MD, Chief Medical Officer, the Multiple Sclerosis Association of America; Director, the Multiple Sclerosis Clinic at Banner University Medical Center; Clinical Professor of Neurology, University of Arizona Medical School
Individualizing treatment
Q: What is your approach to pharmacotherapy for relapsing-remitting MS?
A: My approach, which has evolved over time, has to be modified with every single patient. I began practice before there were any disease-modifying agents; now there are many—and for many patients there is real benefit in the early use of these highly effective agents. For that reason, I have expanded my approach to earlier use of these agents. Often that means more efficacious oral agents and injectable and infused therapies. The final decision is made in collaboration between what you believe the patient will benefit from and what the patient wants to take. The person is the final decider. And the third person in the room is the payer. You and the patient may have made a decision, and that decision may be changed or delayed by the payer. That requires another negotiation. In the end, it is a collaborative process.
—Barry A. Hendin, MD
Addressing cognitive issues
Q: How do you help patients who struggle with cognitive impairment?
A: MS causes inflammation in the brain and spinal cord, and when that occurs it can leave behind permanent scars or holes in brain tissue. Early on in the course of MS, there is a lot of brain reserve—we have more than we need, and for a long time people can do quite well without having symptoms of memory loss. But over time, people find they have issues with finding the right word or keeping up with tasks at work or at home. If that happens, I recommend an assessment by a neuropsychologist to determine which parts of the brain patients are having trouble with. As part of this assessment, patients will be asked about their sleeping patterns, eating habits and mental health. If those issues are playing a role, memory will be worse.
Patients may be referred to a cognitive therapist, who can lead them in a series of challenging tasks to retrain their brain and enhance cognition. Improving nutrition, exercise, reducing stress and increasing social connections can also help boost cognitive reserve.
—Jacqueline Nicholas, MD, System Chief of Neuroimmunology & Multiple Sclerosis at the OhioHealth MS Center, Columbus
Helping patients cope
Q: How do you help patients develop coping strategies for living with MS?
A: The strategies for coping with MS are not solely the work of the neurologist. It involves many people. One strategy is understanding MS better. The better you understand MS, the less frightening it is, and the better you can develop therapeutic and coping strategies.
Some coping has to do with psychological well-being and societal well-being. We must make sure patients are sufficiently protected in their work environment, sufficiently integrated into their community and not disconnected, that their family relations are healthy and strong, that their support network is intact, and that they take an active role in their own MS. That may mean exercising, it may mean seeing a psychologist or psychiatrist, it may mean vocational guidance, and it may mean discussions with the neurologist about problems that exist, so we can be part of the solution.
—Barry A. Hendin, MD
Clinical Minute:
Special thanks to our medical reviewer:
Sylvia Klineova, MD, MS,
Assistant Professor of Neurology at The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York City
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