Collaborative Decision Making Tops Efficacy for MS Patients

When choosing treatment for a patient, whether he or she has a clinically isolated syndrome (CIS) or clinically definite multiple sclerosis (MS), providers need to establish a collaborative relationship, according to speakers at the 2014 Joint ACTRIMS-ECTRIMS Meeting in Boston, Massachusetts, from September 10-13.

Aaron E. Miller, MD, professor of neurology at the Icahn School of Medicine at Mount Sinai and the medical director at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, and Rev. Alasdair Coles, PhD, FRCP, a senior lecturer for the Department of Clinical Neurosciences at the University of Cambridge, held the live symposium “Aligning Treatment Selection with Goals in Multiple Sclerosis: How Can We Optimize Established and Emerging Therapy in Clinical Practice?”

Miller focused on treatment options for and challenges associated with management of patients with CIS and/or MS, while Coles discussed optimizing treatment for highly active disease (HAD) in patients with MS.

As of last year, the way practitioners categorize patients with MS changed. Patients with CIS are those within the spectrum of MS, but who do not meet the diagnostic criteria. However, as soon as they have new disease activity they almost certainly are categorized as having definite or relapse-remitting MS.

“The therapeutic objects for CIS and definite, relapsing forms of MS are similar,” Miller said. “But should we treat CIS? Well, I think now there’s abundant evidence that one should seriously consider treatment and having a conversation with patients.”

For CIS patients, there are 3 available injectable disease-modifying therapies — interferon β-1a, interferon β-1b, and glatiramer acetate — and studies found that all reduced the risk for clinically definite MS by 44-52%.

As for the first of the oral agents, teriflunomide, 14 mg/day reduced the risk of new clinical relapse by 42.6%. The 7 mg/day dose reduced risk by 37.2%. While both options are available in the US, only the higher dose is available elsewhere in the world, too. According to Miller, the only reason anyone should consider the 7 mg dose is if the patient has tolerability issues.

Other agents approved for relapse-remitting MS include: fingolimod, with a reduced ARR of 48-54%; dimethyl fumarate, which reported ARR reduction by 49%; and natalizumab, which reduced ARR by 68%. Although natalizumab reports the highest ARR reduction rate, it has the longest list of potential adverse events, although Miller claimed he seldom encounters many of them. Meanwhile, dimethyl is the least well tolerated, but that can be helped if the patient takes the drug with a real meal. Furthermore, most of dimethyl’s adverse events diminish significantly in 1-2 months.

“I think most important is that the selection of therapy for an individual patient should, in fact, be individualized,” Miller said. “It should be based on a lot of factors, not simply efficacy and not simply safety.”

This is particularly true since factors driving treatment selection vary between practitioners and patients. Although a survey of neurologists listed efficacy as the most important factor when selecting a disease-modifying therapy, followed by safety and tolerability, patients are often more concerned with tolerability, not the nuances of efficacy between drugs. Other factors to consider are how aggressive the disease is and comorbidities.

Both Miller and Coles lamented the lack of head-to-head trials comparing MS drugs. According to Coles, there is also a lack of trials that pick up aggressive subgroups.

There are 2 definitions of aggressive MS: rapidly evolving severe MS, and HAD despite interferon β. However, patients with aggressive MS may not actually fulfill the criteria for either category, which means providers may not be able to escalate therapy as necessary, according to Coles.

Despite the lack of head-to-head trials, he compared the agents indirectly based on available studies: both fingolimod and teriflunomide have been compared to placebo, and teriflunomide has been compared to interferon β-1a subcutaneous, which has been compared to alemtuzumab.

Ultimately, Coles said, alemtuzumab is not only the most effective, but is also the cheapest treatment of MS, according to data from the National Institute for Health and Care Excellence in the United Kingdom. However, the treatment is not licensed in the United States.

Even though a more active disease typically requires more effective therapies with greater risk tolerance, the patient’s perception and attitude to risk is a key determinant in this area, too.

“Not only do we have our technical considerations to take into account, but also the patient’s perceptions of the risk,” Coles said. He added that physicians, nurses, and media heavily influence those perceptions.