Treatment Algorithms

April 2009

Treatment Algorithms in Multiple Sclerosis

Report Authors
Amanda Puffer, M.Sc.
Nathan Calloway, M.A.
Madhuri Borde, Ph.D.

Introduction:

Although multiple sclerosis (MS) afflicts only a small percentage of the U.S. population, the MS market is substantial and growing, owing to the expensive biological therapies that provide a disease-modifying effect and can delay progression of disability and to the anticipated launch of oral disease-modifying drugs within the next two years—a transformative market event. Shifts in medical practice as more primary care physicians (PCPs) become involved with the diagnosis and treatment of MS and increases in the diagnosis of early-stage disease (i.e., clinically isolated syndrome [CIS]) are also contributing to the growth of the U.S. MS market. Interferon-beta (IFN-beta) therapies and the sole agent of the peptide and polypeptide class, Teva Pharmaceutical’s Copaxone (glatiramer acetate), are the mainstays of disease-modifying treatment for MS. While interviewed experts state that Copaxone and Biogen Idec’s Avonex (IFN-beta-1a) are favored in early-line treatment, our 2009 analysis of patient-level claims data reveals that Merck Serono/Pfizer’s Rebif (IFN-beta-1a) also plays a critical role in the treatment of newly diagnosed patients, as physicians are becoming more aggressive about turning to high-dose, high-frequency IFN-beta therapies in earlier lines of treatment. Using patient-level claims data, as well as insight from 151 surveyed U.S. neurologists and PCPs, this report determines the share of each currently marketed drug by line of therapy, analyzes the factors driving physicians to choose key disease modifiers over others, and details how physicians predict that this dynamic will change over the next two years with the expected approval of the first oral disease-modifying agents, starting with Merck Serono’s oral cladribine and Novartis/Mitsubishi Tanabe’s fingolimod (FTY-720) in 2010 and 2011, respectively.

Questions Answered in This Report:

  *   Lines of therapy: Data contained in this report show that as patients are increasingly diagnosed earlier in the progression of their disease, those therapies with moderate efficacy and less frequent dosing and/or benign side effect/safety profiles continue to receive greater use in earlier lines of treatment. What is the treatment initiation rate for newly diagnosed MS patients? How do the early-line patient shares for Copaxone, Avonex, Rebif, and Betaseron compare? What are the retention rates of each of the IFN-betas and Copaxone in the first year after diagnosis?

  *   Pathways to key therapies: Physicians (and patients) consider agents’ side effects, efficacy, and ease of use when deciding among the disease-modifying therapies and, along with an individual’s response to a given therapy, these factors drive differences in switching rates among key therapies. What percentage of the total use of each IFN-beta and Copaxone is attributed to each line of therapy? What percentages of the patients who start Copaxone versus Avonex, Rebif, or Betaseron do so after another disease-modifying drug? What do these patterns suggest about each agent’s positioning relative to other disease modifying drugs? Which agents most frequently precede the use of Biogen Idec/Elan’s Tysabri (natalizumab)? How has Tysabri’s use in the MS treatment paradigm evolved since last year’s report?

  *   Physician behavior: Physicians surveyed for this report indicate that neurologists make the primary treatment decisions for the majority of MS patients, most often initiating treatment with tolerable therapies of moderate efficacy (i.e., Avonex or Copaxone) in patients with moderate disease. What differences underlie PCPs’ and neurologists’ diagnosis and treatment of newly-diagnosed patients? How does treatment initiation differ for patients of different MS subtypes (e.g., relapsing-remitting MS [RR-MS] and CIS)? Which factors are the most critical differentiators when physicians are deciding between Avonex and Copaxone, Rebif and Betaseron, and Rebif and Avonex? What do physicians cite as the most common reasons to switch patients to a new disease modifier after Avonex versus Copaxone, and which disease-modifier is most frequently selected? How do these reasons compare with the factors most likely to cause a switch among patients treated with Rebif or Betaseron?

  *   Forecast: Increasing comfort among physicians with high-dose IFN-beta therapy and two emerging therapies—both offering an advantage in delivery and one in efficacy—are expected to steal patient share of currently available disease-modifying therapies. How will neurologists and PCPs shift their prescribing of current disease-modifying therapies over the next two years? How will the emerging therapies Merck Serono’s oral cladribine, Novartis/Mitsubishi Tanabe’s fingolimod (FTY-720), and BioMS Medical/Eli Lilly’s dirucotide (MBP-8298) be integrated into the MS treatment paradigm? Which current drugs are most likely to be replaced by each of these emerging drugs?

Scope:

Primary research: Quantitative results from our survey of 151 physicians (76 neurologists and 75 PCPs):

- Physician opinion on how drug use differs by patient severity.

- Most influential drug attributes when physicians choose between agents.

- Anticipated changes in the line of therapy in which physicians use key agents.

Primary patient-level data: Quantitative findings from our analysis of data covering 61 million lives from 98 geographically diverse U.S. health plans:

- Quantified lines of therapy analysis showing exact share of each agent in each line of therapy, including rate of progression between lines and length of time patients are on each line.

- Progression flowcharts through one year of treatment for newly diagnosed patients receiving each of the following first-line agents: Avonex, Rebif, Betaseron, Copaxone, Tysabri, Rituxan, corticosteroids, CellCept, azathioprine, mitoxantrone, methotrexate, and cyclophosphamide.

- Flowcharts tracking the preceding therapy patterns for patients taking each of the following key therapies: Avonex, Rebif, Betaseron, Copaxone, Tysabri, Rituxan, corticosteroids, Cellcept, azathioprine, and mitoxantrone.

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