Multiple Sclerosis: Evolving Approaches to Treatment

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Regarded as the leading progressive neurological disease affecting young adults, multiple sclerosis (MS) often strikes during life’s pivotal moments—when individuals are embarking on careers or starting families. The global prevalence of MS is rising, particularly affecting women. In the US alone, over a million people grapple with its often-debilitating effects. Alongside the physical and emotional toll MS exacts, patients and healthcare systems face mounting financial pressures, with treatment costs varying considerably depending on the type and stage of intervention.

MS arises when an individual’s immune system targets their central nervous system (CNS), impacting the brain, spinal cord, and optic nerves. Early symptoms might include eye pain or blurred vision due to optic neuritis, potentially escalating to vision loss. Symptoms stemming from spinal cord inflammation can range from numbness and tingling to walking difficulties and bladder issues. As the disease progresses, pain, fatigue, depression and even sexual dysfunction can manifest, with aggressive MS forms resulting in even more severe symptoms.

The Four Distinct Types of MS

There are four primary multiple sclerosis classifications, each indicating the disease’s progression stage. Identifying the type aids in guiding treatment choices and forecasting long-term outcomes.

  1. Clinically isolated syndrome (CIS): An initial neurological episode, lasting at least 24 hours, caused by inflammation and demyelination in the central nervous system. While symptoms, such as vision problems and weakness, resemble MS, not everyone with CIS progresses to full-blown MS.
  2. Relapsing-Remitting Multiple Sclerosis (RRMS): The most prevalent form, RRMS sees patients undergoing periods of relapses, followed by periods of recovery. RRMS accounts for about 85% of all MS diagnoses.
  3. Secondary-Progressive MS (SPMS): Over time, a significant portion of those with RRMS will transition to SPMS, where symptoms progressively worsen during relapses. This transition typically occurs 10 to 20 years after the initial onset.
  4. Primary-Progressive MS (PPMS): Differing from the relapsing forms of disease, individuals with PPMS witness a consistent and gradual progression of symptoms, without experiencing distinct periods of remission. As symptoms manifest in PPMS, neurological function can decline rapidly, with disabilities accumulating.
Current Treatment Options & Their Costs

Disease modifying therapy (DMT) is currently the first line of treatment for MS. These treatments use various mechanisms of action to modify immune processes to decrease inflammation and prevent further damage to the central nervous system.

Beta Interferons

In 1993, Betaseron (interferon beta-1b) received FDA approval, heralding the era of beta interferons as the first DMT for RRMS. Even after three decades since its introduction, Betaseron maintains premium positioning with a Wholesale Acquisition Cost (WAC) of $119,939 per year.

Other notable beta interferon agents include:
  • Avonex (interferon beta-1a) [WAC $103,323/yr]
  • Rebif (interferon beta-1a) [WAC $128,971/yr]
  • Extavia (interferon beta-1b) [WAC $93,819/yr]
  • Plegridy (peginterferon beta-1a) [WAC $103,323/yr]

These treatments necessitate self-injection, which can pose challenges for MS patients. Moreover, multiple studies have underscored the superior efficacy of newer agents against these time-honored beta interferons.


Copaxone (glatiramer acetate) [$75,816/yr] is a cornerstone in RRMS treatment, not only because of its proven efficacy but also due to its more affordable generic counterpart [WAC $20,535/yr].

S1P Receptor Modulators: A Shift in MS Treatment

Gilenya (fingolimod) [WAC $126,813/yr], was introduced as the very first oral DMT, simplifying the medication process for MS patients, removing the challenges of injections. Its generic alternative offers a significant price reduction with a WAC of $8,030/yr.

The other S1P receptor modulators are priced closer to branded Gilenya which include Mayzent (siponimod) [WAC $112,346/yr], Zeposia (ozanimod) [WAC $102.038/yr], Ponvory (ponesimod) [WAC $110,916/yr], and Tascenso ODT (fingolimod) [WAC $126,813/yr].


Aubagio (teriflunomide) [WAC $113,707/yr] was the second oral treatment for MS. Unfortunately, Aubagio has an increased risk of fetal abnormalities which applies to both women and men who take the medication, thus requiring the use of contraceptive measures to prevent pregnancy for anyone taking it. Just recently, a less expensive generic version was launched at a heavily discounted WAC of $1,099/yr.

Fumaric Acid Esters

Tecfidera (dimethyl fumarate) [WAC $109,441/yr] was the first of three oral fumaric acid esters used to treat MS. It’s known to be associated with gastrointestinal (GI) side effects, which are typically minimized after a month. Tecfidera has a generic version available on the market with a deeply discounted WAC of $1,105 per year.

The other two agents in this class are Vumerity (diroximel fumarate) and Bafiertam (monomethyl fumarate). Both Vumerity [WAC $100,516/yr] and Bafiertam [WAC $76,930/yr] are improved formulations of Tecfidera with a lower incidence of GI side effects.

High Efficacy Therapy

These agents are recognized as high-efficacy therapies (HETs) for their superior ability to treat MS. Experts use the HET designation to guide the management of patients with highly active disease. Despite varying opinions on HET designation, these agents have consistently proven their effectiveness, especially in patients who didn’t respond to other DMTs. While some HETs employ a targeted approach to optimize results and minimize side effects, balancing efficacy and safety remains challenging due to potential toxicities with these agents.

Monoclonal antibodies
  • The first monoclonal antibody FDA approved for MS was Tysabri (natalizumab) [WAC $113,771/yr]. It faced a brief market withdrawal in 2005 due to concerns over a fatal brain infection but returned with a black-box warning and a new indication restricting its use to second-line therapy. It’s administered intravenously at medical facilities.
  • Considered the market leader of the HETs, Ocrevus (ocrelizumab), priced at [WAC $75,102/yr], is the exclusive treatment for PPMS. It’s also used to treat other relapsing forms of MS. This biannual intravenous treatment offers patients convenience.
  • Kesimpta (ofatumumab) [WAC $97,969/yr] treats relapsing MS forms. It shares a mechanism with Ocrevus but stands out as a self-administered monthly subcutaneous injection.
  • The newest monoclonal antibody, Briumvi (ublituximab)[WAC $59,000/yr], utilizes the same mechanism of action as Ocrevus and Kesimpta. It is an intravenous infusion which requires administration by a healthcare provider twice a year but has a much shorter infusion time compared to Ocrevus.
  • Lastly, Lemtrada (alemtuzumab) [WAC $113,771/yr], an annual intravenous infusion with daily doses across three days, carries serious potential side effects. It’s typically a fallback after two other DMTs have failed.

Mavenclad (cladribine) [WAC $137,566/yr] is the sole orally administered HET for relapsing MS but is not recommended for CIS due to safety concerns. Its unique dosing is limited to a maximum of two years of therapy with doses given in short cycles. While highly effective, safety concerns about potential malignancy and fetal risks restrict its use to a narrow patient population.

Evolving Treatment Strategy

The journey to select the right disease-modifying therapy (DMT) for newly diagnosed MS patients is riddled with complexity and debate. Most concur that the decision should be highly individualized, considering each patient’s unique history and clinical nuances. Although early DMT interventions can potentially delay the progression of MS and curtail treatment costs, the road to optimal care isn’t straightforward. Traditionally, a phased approach to treatment began with standard therapies, transitioning, if necessary, to high-efficacy therapy (HET). But mounting evidence underscores the advantages of introducing HETs earlier to stave off significant neurological damage. Despite the undeniable benefits, the soaring costs of HETs, often ranging between $50k to $140k annually, pose a significant barrier. Many insurance providers mandate patients to initially try lower-cost DMTs before sanctioning HET coverage. As more data surfaces emphasizing the superiority of HETs and insights into predicting clinical outcomes evolve, it will increasingly challenge this typical phased approach to treatment. Moreover, emerging studies suggesting possible long-term cost efficiencies with early HET adoption will add another layer of complexity. The continued need exists for clinical trials and studies using real-world data to provide patients with the best treatment options for management of this life-altering condition.


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  4. Wylezinski LS, Gray JD, Polk JB, Harmata AJ, Spurlock CF III. Illuminating an invisible epidemic: a systemic review of clinical and economic benefits of early diagnosis and treatment in inflammatory disease and related syndromes. J Clin Med. 2019;8:493.



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