The field of multiple sclerosis (MS) treatment now offers a variety of medications—from longer-in-the-market agents now available also in generic formulations, to several more recent additions to the armamentarium—and all have distinct modes of action. However, while treatment choices have become more numerous, prices for such medications have risen at a breathtaking rate far beyond that of inflation. Ahead, I will review the factors impacting drug costs and consider how the changing economic landscape of MS therapy will shape future development and care.

“Preferred” by Whom?

A number of factors can influence the cost of a drug. Medication purchases by Federal carriers may be subject to mandated rebates and/or penalties that depend on how long a specific product has been on the market, while commercial purchasers of medications negotiate rebates on individual products and on volume of purchases from a given manufacturer that principally change the effective cost of a medication from a payer side. This leads to a situation in which the effective cost of a medication may be significantly different depending on the payer.

For patients, arguably the most important facet of the complicated puzzle of drug prices is the tiered system of “preferred,” “non-preferred,” and “uncovered” formularies. Under this system, a pharmacy benefit provider contracted by an insurer sets what is “preferred,” “non-preferred,” or “uncovered,” based on a number of considerations, not least of which are financial factors. This model risks supplanting evidence-based medical considerations with pricing arguments for the drug alone, but it fails to consider total cost of treatment or consequence of undertreated disease.

While insurance companies have used the formulary model for many years, recent changes have made the system far more concerning for patients. In the past, when there were changes to the formulary, there was generally a grandfathering or an exemption to allow continuation of a previous formulary medication for patients who enjoyed reasonable clinical stability on the agent they were already on. However, in a very concerning recent trend, insurance companies have started to step back from honoring this grandfathering process less frequently, effectively forcing patients to switch to a medication with different mode of action and in certain cases even to a class of medication that the patient had previously failed. Such policies make little sense from an evidence-based perspective.

For example, a patient that had previously experienced breakthrough on a high-dose interferon agent may have to use another manufacturer’s high dose interferon because patients are required to have used “preferred” products before other MS medications are to be approved. It does not appear that rational treatment considerations are driving such formulary policies, rather price is.

A patient is rather less likely to benefit from a therapeutic mode of action that was previously not effective or not tolerable. Another concern is the frequency and the breadth of formulary changes. Case in point are the many changes in formulary status of MS medications that became effective in 2016. Obviously, even most casual observers would draw the conclusion that effective cost rather than efficacy was at the center of these formulary switches.

To offset at least in part some of the cost sharing of medication cost borne by patients, many manufacturers provide programs that help eligible patients with copays and co-insurance and contribute to charities that help patients on Medicare struggling with their portion of medication cost. Many manufacturers also have programs that provide eligible patients affected by formulary changes to receive free or low-cost medication while denials are re-evaluated. Drug manufacturers carry the costs for these programs. Of note, patients with high co-insurance may be disproportionally hit with increasing drug prices. Often, co-insurance is calculated not based on cost to the pharmacy benefit provider after rebates but on manufacturer retail price. Patients with co-insurance may thus actually carry a larger share of the actual cost medication.

Practical Pointers

• In the instance that an insurer does not “prefer” a particular agent you have prescribed, the National MS Society has put together template letters of appeal that are available on the society’s website (www.nationalmssociety.org).

• To help defray the costs of a medication, consider enrolling patients in manufacturer support programs where available.

Impact on MS Therapy

Looking at the dense marketplace of MS medications, the volatility of the reimbursement spectrum and insurance formularies spells great uncertainty for patients. When a widely used product loses its preferred status, the simple reality is that a potentially larger group of patients faces either higher cost-sharing or may be forced to switch to another therapy. While changing between agents that share the same mode of action comes with its own set challenges, it is arguably more unpredictable to switch to an agent with an altogether different mode of action that’s deemed more “preferable” economically.

While individual practitioners may have their own hierarchy of effectiveness of MS agents, factors such as the variability of the disease, different patient characteristics, and risk and side-effect profiles of individual agents stand in the way of a simple first-line, second-line, etc. algorithm. With the economics of therapy selection taking priority over clinical considerations, it is frustrating to see a therapeutic choice deemed appropriate for a given patient to be beyond formulary reach. This is especially important as it has become better understood that there is a window of opportunity early in the MS process during which effective treatment may significantly affect a patient’s trajectory for years to come, while delayed treatment may leave the patient with potentially avoidable disability. Restricted, cost-based formularies may potentially be far less cost-effective, as delay of the most appropriate medication for a given patient may ultimately lead to increased overall treatment cost and burden of disease.

MS is a chronic condition that patients live with for the rest of their lives. Thus, rather than looking at an episodic treatment model, it may make sense both clinically and economically to consider the long-term implications of care. Thus, it will become important to accumulate more outcome data that may ultimately put a stronger emphasis on patients who are not cared for as optimally as possible, which ultimately results in greater cost of treatment and other disease-associated cost. While this would represent a shift from the current model payers attribute to MS treatments, such a model could very well lower longer-term system utilization while achieving better outcomes. The current model of percolating patients through agents based on economic considerations and switching when a given treatment failed may risk avoidable setbacks, as breakthrough disease is in general a model where patients are not controlled. It could be that a given patient has difficult to control disease, but in many cases the right intervention may help stabilize the patient. Therefore, it behooves us to institute changes in our treatment models that would better enable us to treat optimally from the very beginning of the disease and shift the decision back to a cooperative decision-making between patient and physician.

Advocating for Appropriate MS Care

Even in an ideal scenario, optimal treatment for MS across the board would be a challenge. But given the current conditions (including tighter and more tightly enforced restrictions on drug formularies), delivering the appropriate care to patients can be an act of resistance against a system that’s designed to run on short-term economic considerations. Although the MS treatment field has expanded significantly in recent years and continues to be a place of great innovation, access to the best treatment has unfortunately not kept pace. There may be an increase in choice for medications with new treatment modalities with distinct features, but this may result in a decrease in what’s available and/or affordable to patients at a certain time.

The time necessary to wade through mounting regulations and pre-certification requirements has increased at a time when reimbursements have not. Even if we were to fight for approval on certain agents, physicians ultimately have no choice but to prescribe a medication that the patient has access to and can afford. Oftentimes just copays are already a challenge for patients, especially since many are on several medications, including those for disease associated symptoms that are all subject to copays and possibly co-insurance.

That having been said, while the practice of principally replacing the model of evidence-based medicine with a rebate-based model is difficult to withstand, but it is the role of the physician to point out the possible shortcomings of this approach. Individual physicians and physician groups should advocate for action that gives the decision regarding how to best treat MS back to patients and physicians.

Moreover, in spite of increased administrative and regulatory burden of caring for MS patients, physicians and subspecialty medical providers remain likely the last, best advocates for patients. It may be an uphill battle, but opportunities are available that physicians can take advantage of. As long as there is a strong proprietary interest from manufacturers within the MS space, there should be a shared interest in delivering specific products that are deemed most appropriate for an individualized care approach. There are support mechanisms that specific manufacturers have put together that could help patients during formulary transitions to continue to allow access to a given medication. There are also a number of tools and resources that assist physicians and their staff to deal with utilization reviews and denials can offer to patients that could be beneficial, as well. For example, the National MS Society (www.nationalmssociety.org) has put together templates for letters including appeal letters to insurance companies when a medication choice is denied. Additionally, the American Medical Association, the Academy of Neurology, the Consortium of MS Centers, the MS Association of America, and the MS Foundation can help physicians to advocate for care and are in many cases good sources for disease related information. Such information can also be found on the NIH website.

Physicians should also remain open to an ongoing dialogue with insurance providers to educate them about the concept of the window of opportunity and that the most effective early interventions can lead to both clinically efficacious and cost-effective care.

relieving the cost burden

In MS, clinicians have a unique opportunity early in the disease stages to possibly affect the ultimate outcome of the condition or in the least allow a patient faced with this disease to live the fullest and most productive life possible. We have learned that the right treatment at the right time can translate to significant clinical benefit to patients. Therefore, as MRI and other imaging modalities continue to improve, allowing us to assess even clinically silent disease activity with greater accuracy, and as new therapeutic modalities expand the treatment arena, clinicians should be in the position to use the mot appropriate available tool to ensure that patients receive the best possible treatment. The available MS medications fold into therapeutic categories that have different modes of action. If a patient shows breakthrough disease activity during routine monitoring it is reasonable to consider a switch to an agent of a distinct mechanism of action or perhaps consider a dose escalation if this is available. However, while clinicians can make every effort to work within the current framework to secure the best treatment for patients, it is a growing concern that the odds are increasingly stacked against the practice of evidence-based medicine. Fortunately, there are ways that we can try to help eligible patients secure more affordable yet still efficacious treatment. These include enrolling them in manufacturer support programs and directing them toward other resources of advocacy groups. As we move forward, it is our responsibility to continue to draw attention to these issues and ensure through dialogue and advocacy that patients with chronic conditions requiring ongoing treatment such as MS are not buried by cost-shifting.

Patients with MS deserve the best treatments available, and they deserve access to these treatments in a way that they can afford. As their providers, we must advocate both for the sound practice of evidence-based medicine and for the welfare of our patients. n

Thomas P. Leist, MD, PhD is a Professor of Neurology and Director of the Comprehensive Multiple Sclerosis Center at Thomas Jefferson University in Philadelphia, PA.