The Provider and Caregiver Connection: Multiple Sclerosis: A Treatment Paradigm Shift When “Time Is Brain”
Release Date: April 30, 2018
Expiration Date: April 30, 2019
Media: Internet - based
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Common symptoms, including impaired mobility, loss of sensory function, cognitive decline, emotional stress, and changes in bladder function, can significantly reduce patients’ quality of life. MS is currently an incurable disease, but improved understanding of disease pathophysiology has contributed to the development of a range of disease-modifying therapies (DMTs) that can improve long-term clinical outcomes. The wide variety of available treatments also means that patients and providers can weigh the benefits and risks of each therapy as part of shared decision-making strategies. Educating patients about their disease is critical to build a foundation of knowledge that can aid in these shared decision-making discussions.
The primary goals of MS treatment are to slow disease progression, prevent relapses, manage symptoms, and improve patients’ health-related quality of life. MS progression and prognosis is highly variable, so individualized approaches to treatment are essential. Early, aggressive treatment and care provided by a comprehensive, patient-centered multidisciplinary team can optimize long-term clinical outcomes and maximize health-related quality of life.
This Provider and Caregiver Connection™ provides a two-fold activity. First a patient with MS and their caregiver engage in a discussion with a neurologist and a nurse practitioner specializing in neurological rehabilitation. Topics in this straightforward, impactful discussion include initial diagnosis, importance of multidisciplinary team interaction and practical, proactive lifestyle adjustments and ways to overcome challenges. In the second part, a multidisciplinary team individually answers questions - from early, efficacious treatment, new and emerging disease modifying therapy (DMT) to treatment escalation, all with a patient-centered approach.
Acknowledgement of Commercial Support
Instructions for This Activity and Receiving Credit
This CME activity is intended for neurologists, primary care physicians, nurse practitioners (NPs), nurses, and physician assistants (PAs) involved in the treatment and management of patients with multiple sclerosis (MS). Psychiatrists and other health care professionals interested in the treatment of MS may also participate.
Upon completion of this CME activity, you should be better prepared to:
- Describe the concept of neurological reserve and the impact of early, efficacious treatment
- Identify appropriate patient resources to improve disease knowledge, symptom reporting and treatment options
- Review the mechanisms of action (MOA)s and safety considerations for each disease modifying treatment (DMT)
- Articulate considerations and timing when switching to a new treatment
- Model a multidisciplinary treatment strategy to improve the management of patients with MS
Faculty, Staff, and Planners' Disclosures
James M. Stankiewicz, MD
Partners Multiple Sclerosis Center
Assistant Professor of Neurology
Harvard Medical School
Brigham and Women’s Hospital
Lynn Stazzone RN, MSN, NP, MSCN
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Penny Tenzer, M.D.
Professor of Clinical Family Medicine
Vice Chair of Academic Affairs
Medical Director, UHealth at Walgreens Clinics
Department of Family Medicine and Community Health
University of Miami, Miller School of Medicine
Patient with Multiple Sclerosis
The staff of PER® have no relevant financial relationships with commercial interests to disclose.
Disclosure Policy and Resolution of Conflicts of Interest (COI)
As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.
Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.
Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians, and is a provider approved by the California Board of Registered Nursing (CBRN).
Physicians' Education Resource®, LLC designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credits™ and for 2 contact hours for nurses. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Off-Label Disclosure and Disclaimer
This activity may or may not discuss investigational, unapproved, or off-label uses of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to the diagnostic, treatment, and management options for a specific patient’s medical condition.
The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource®, LLC, or any of the companies that provided commercial support for this activity.
PER Pulse™ Recaps
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Importance of Early, Efficacious Treatment of Multiple Sclerosis
- Increasing evidence suggests that early, effective treatment of multiple sclerosis can prevent inflammatory events that lead to a progressive disease course
- Early use of highly efficacious disease-modifying therapies, such as natalizumab, alemtuzumab, and ocrelizumab, can provide long-lasting immunosuppression
- Many practitioners now recommend highly efficacious disease-modifying therapies as first-line treatment for patients with highly active disease and poor prognostic factors
Over the past several years, the multiple sclerosis (MS) treatment landscape has changed dramatically. As discussed in this Provider and Caregiver Connection, a patient diagnosed with MS in the year 2000 had just a few choices for initial therapy, all of which had only modest efficacy against disease progression. In contrast, today there are 15 different disease-modifying treatment (DMT) options for MS, several of which have demonstrated superior efficacy compared with traditional therapies.
Despite the expanded range of MS treatment options, many patients and health care providers still prefer to use first-generation DMTs (ie, interferon beta or glatiramer acetate) as initial therapy because these agents have well-established, favorable, long-term safety profiles, with low risk of serious adverse events. However, in his clinical practice, James Stankiewicz, MD, has observed that MS is “a consistently progressive disease for many patients.” Furthermore, Dr. Stankiewicz notes that even in the early stages of disease, when symptoms may be minimal and damage may not be evident with conventional magnetic resonance imaging (MRI), inflammation and irreversible neurodegeneration can negatively affect patients’ long-term prognosis, increasing their risks for functional disability and cognitive impairment. Thus, his guidance is that “the only way you can be more sure that patients may do better over the future is to use highly effective agents first—if you don’t expect that those highly effective treatments are going to create a lot in the way of side effects relative to lower efficacy agents.” Consistent with this guidance, many practitioners are now recommending the use of more potent drugs, such as natalizumab, alemtuzumab, and ocrelizumab, as first-line therapy for patients with highly active disease and poor prognostic factors because these agents provide highly efficacious, long-lasting immunosuppression.1
The use of high-efficacy treatment strategies is supported by findings from a recently published systematic review. In this review, Merkel and colleagues analyzed results from clinical studies reporting treatment outcomes with high-efficacy immunotherapies, including natalizumab, alemtuzumab, and fingolimod. Across the identified publications, early use of high-efficacy treatment was associated with clinically meaningful suppression of relapse activity compared with delayed use of high-efficacy treatments.1 Similarly, early use of the high-efficacy immunotherapy ocrelizumab has been shown to provide profound reductions in clinical and subclinical disease activity compared with interferon beta-1a in patients with relapsing forms of MS. Specifically, over 96 weeks of treatment, the percentage of patients achieving no evidence of disease activity (defined as no 12-week confirmed disability progression, no relapses, no new or enlarging T2 lesions, and no T1 gadolinium-enhancing lesions) increased by 75% with ocrelizumab compared with interferon beta-1a.2References
- Merkel B, Butzkueven H, Traboulsee AL, Havrdová E, Kalincik T. Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: a systematic review. Autoimmun Rev. 2017;16(6):658-665. doi: 10.1016/j.autrev.2017.04.010.
- Havrdová E, Arnold DL, Bar-Or A, et al. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult Scler J Exp Transl Clin. 2018;4(1). doi.org/10.1177/2055217318760642.
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Treatment Escalation in Patients with Multiple Sclerosis
- Treatment escalation should be considered for patients who experience multiple sclerosis (MS) relapses, worsening disability, cognitive changes, or new or enlarging lesions on magnetic resonance imaging
- Practical considerations when selecting more potent therapies include the patient’s medical history, comorbidities, and plans for pregnancy
- Information is limited on the best sequence of treatments to use in patients with relapsing forms of MS; however, many experts recommend attainment of tight disease control with highly effective agents as soon as possible after MS diagnosis
Traditionally, the most common MS treatment strategy is an escalation approach, in which patients start treatment with a first-generation disease-modifying therapy (DMT), such as interferon beta or glatiramer acetate, and then switch to more potent drugs, as needed, when they experience breakthrough disease activity or suboptimal treatment response. Clinical parameters that can be indicative of suboptimal treatment response include occurrence of relapses, worsening disability, cognitive changes, and new or enlarging lesions on magnetic resonance imaging (MRI).
There are several practical factors that should be considered once a clinical decision has been made to switch a patient’s treatment to a more efficacious DMT. Personal and family medical history and comorbidities should be considered. For example, as Lynn Stazzone, NP, noted in this activity, a patient with a family history of breast cancer may choose not to switch to ocrelizumab because a safety signal for breast cancer was observed in clinical trials with this drug.1 She also provided guidance that treatment with fingolimod is likely not a good choice for a patient with comorbid diabetes because diabetes increases risk for macular edema, which is a known dose-dependent side effect of fingolimod.2 All patients should be screened for the presence of John Cunningham virus (JCV) antibodies, which are associated with increased risk of progressive multifocal leukoencephalopathy (PML), most notably with natalizumab. Additionally, it is important to consider the need for a washout or elimination period before initiating new therapy. In his clinical practice, James Stankiewicz, MD, has found that “we've learned that it's not a good idea to wait too long [before initiating new therapy], because if you wait too long, patients can experience disease activity.” While no washout period is needed when discontinuing interferon beta, glatiramer acetate, or dimethyl fumarate products, the suggested washout periods with fingolimod, natalizumab, and ocrelizumab are 1 to 3 months, and teriflunomide may take up to 2 years to clear for some patients. The need for a washout period is not known with alemtuzumab.3
When considering DMT sequencing, it is particularly important to understand the risks associated with different therapies for women who may become pregnant. While no DMTs are FDA approved for use during pregnancy, data suggest that interferon beta and glatiramer acetate may be safe for women who may want to pursue pregnancy. For newer DMTs, use of contraception is required for women with childbearing potential. In addition, a negative pregnancy test is required before prescription of teriflunomide because this agent was shown to be teratogenic and embryo-lethal in animal studies.4
Information is limited on the best sequence of DMTs to use in patients with relapsing forms of MS. However, as data continue to emerge on the benefits of early, aggressive intervention to prevent permanent disability and irreversible axonal loss, many experts are now recommending attainment of tight disease control with highly effective agents as soon as possible after MS diagnosis.5,6References
- Montalban X, Hauser SL, Kappos L, et al; ORATORIO Clinical Investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. doi: 10.1056/NEJMoa1606468.
- Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology. 2012;78(9):672-680. doi: 10.1212/WNL.0b013e318248deea.
- Miller AE. Switching or discontinuing disease-modifying therapies for multiple sclerosis. Continuum (Minneap Minn). 2016;22(3):851-863. doi: 10.1212/CON.0000000000000327.
- Lu E, Wang BW, Guimond C, et al. Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance. Expert Rev Neurother. 2013;13(3):251-260; quiz 261. doi: 10.1586/ern.13.12.
- Boggild M. Immunosuppression followed by immunomodulation. J Neurol Sci. 2009;277(suppl 1):S50-S54. doi: 10.1016/S0022-510X(09)70014-0.
- Boster A, Edan G, Frohman E, et al. Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. Lancet Neurol. 2008;7(2):173-183. doi: 10.1016/S1474-4422(08)70020-6.
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Multidisciplinary Management of Multiple Sclerosis
- Optimal multiple sclerosis disease management requires input from a multidisciplinary team of health care professionals who are focused on providing patient-centered care
- Key members of the multidisciplinary team can include neurologists, nurses, other medical specialists, physical and occupational therapists, and counselors
- Working together, the multidisciplinary team can proactively address issues as they arise
Patient-centered care is essential for optimizing long-term clinical outcomes and health-related quality of life for patients with multiple sclerosis (MS). Because the disease affects numerous body systems and functions, and patients with MS are at increased risk for various comorbidities, a multidisciplinary team approach to disease management is the best way to ensure that patients are receiving comprehensive, continuous care.1
In a multidisciplinary team, the neurologist obviously plays the most central role in working with the patient to prevent disease progression and manage symptoms of MS. Nurse practitioners are valuable providers of disease-related education and can spend time answering patients’ questions and explaining the benefits and potential adverse effects of different MS treatment options. Primary care physicians play an important role in ensuring that patients are receiving recommended preventive care (eg, cancer screenings, vaccinations), as well as screening for and management of comorbidities such as hypertension, diabetes, dyslipidemia, hypothyroidism, etc. Depending on patient characteristics and disease features, various specialists should also be members of the multidisciplinary team. For example, patients with bladder symptoms, such as urinary incontinence, should be referred to a urologist.
Many patients find physical and/or occupational therapy to be valuable components of their care, helping them improve their strength, aerobic capacity, range of motion, posture, and joint mobility, and reducing gait dysfunction, fatigue, and spasticity. Oftentimes, such therapy can be provided in a group setting, allowing patients to interact and share experiences with other people with MS in a supportive environment. For example, the patient Mike, in this Provider and Caregiver Connection, said that in his total rehab physical therapy, “Everybody knows what everybody else is dealing with. It’s a great place.” Vocational rehabilitation services can help patients obtain or maintain employment and live more independently.2 Physical therapists or physiatrists can provide recommendations for appropriate mobility aids (eg, canes, wheelchairs, scooters) and for making patients’ home environment more accessible.3 Consultation with an orthopedist can provide patients with strategies to improve balance and reduce risks of falling and osteoporosis. If patients with MS do experience fractures as a result of falling or osteoporosis, expert care from an orthopedist can facilitate complete recovery and prevent long-term complications.4
Cognitive changes associated with MS cause many patients to develop speech abnormalities, such as dysarthria, which can be managed by a speech-language pathologist.5 Psychological symptoms are quite common in patients with MS, with half of patients experiencing clinical depression at some point during the course of their illness.6 As part of the multidisciplinary team, psychologists, neuropsychologists, and social workers can help recognize signs and symptoms of depression, and provide support for patients who may feel isolated or stigmatized. When pharmacologic intervention for depression is warranted, psychiatrists can evaluate patients and work with them to develop a treatment plan.References
- Coyle PK, Perrin Ross A, Turner AP, Cohen B, Traboulsee AL. The multidisciplinary team in multiple sclerosis: harnessing the array of diagnostic and therapeutic tools to improve quality of life. MedScape CME/CE. Released August 18, 2008. medscape.org/viewarticle/579236. Accessed May 13, 2018.
- Chiu CY, Chan F, Bishop M, da Silva Cardoso E, O’Neill J. State vocational rehabilitation services and employment in multiple sclerosis. Mult Scler. 2013;19(12):1655-1664. doi: 10.1177/1352458513482372.
- Iezzoni LI, Rao SR, Kinkel RP. Experiences acquiring and using mobility aids among working-age persons with multiple sclerosis living in communities in the United States. Am J Phys Med Rehabil. 2010;89(12):1010-1023. doi: 10.1097/PHM.0b013e3181f70292.
- Pidgeon TS, Borenstein T, Daniels AH, Murali J, Hayda RA. Understanding multiple sclerosis: essentials for the orthopaedic surgeon. JBJS Rev. 2014;2(7). pii: 01874474-201402070-00005. doi: 10.2106/JBJS.RVW.M.00120.
- Rodgers JD, Tjaden K, Feenaughty L, Weinstock-Guttman B, Benedict RH. Influence of cognitive function on speech and articulation rate in multiple sclerosis. J Int Neuropsychol Soc. 2013;19(2):173-180. doi: 10.1017/S1355617712001166.
Minden S, Turner A, Kalb R, Burke D. Emotional disorders in multiple sclerosis. National Multiple Sclerosis Society website.
nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical-Bulletin-Emotional-Disorders-5-5-14.pdf. Accessed May 13, 2018.
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