Conference Coverage

Changing Therapies May Benefit Patients With Active MS



BOSTON—Neurologists may consider changing the medication for a patient with relapsing-remitting multiple sclerosis (MS) who has ongoing disease activity despite treatment, according to a presentation at the 2014 Joint ACTRIMS–ECTRIMS Meeting. Patients with a poor response to their initial treatment often benefit from a change to a new drug.

“The rationale for escalating treatment strategies in MS is based on a combination of clinical experience, expected benefit, and calculated risk,” said Xavier Montalban, MD, Chair of Neurology and Neuroimmunology at University Hospital and Research Institute, Vall d’Hebron in Barcelona. Yet neurologists must remember that “we do not have good class I evidence for switching patients from a platform therapy to a second-line treatment strategy,” he added.

Assessing Treatment Response
Treatment response is a major element of a treatment algorithm and can be defined in various ways. A common definition includes two clinical parameters (ie, relapses and disability progression) and MRI activity.

In an article published in Multiple Sclerosis in 2009, Río et al proposed a multicomponent score to assess treatment failure. The Río score incorporates the following three criteria: one or more relapse during the first 12 months, an increase in Expanded Disability Status Scale (EDSS) score of one point that is confirmed at six months, and three or more active new T2 or gadolinium-enhancing lesions on MRI. The authors found that patients who met two of these criteria had an odds ratio (OR) of 5.9 for clinical activity within three years. Fulfilling all three criteria was associated with an OR of 13.2 for this outcome.

Río and colleagues recently completed a study examining potential predictors of long-term outcomes. The investigators monitored clinical activity among 234 patients with MS during the first two years of treatment with interferon beta. They followed patients for 12 years and tracked three outcomes: the development of progressive MS, confinement to a wheelchair, and an increase in EDSS score of 5 or more points. The researchers found that clinical activity during the first two years of treatment increased the likelihood of the three end points at 12 years. These results are consistent with those of a 2013 study by Bermel et al, said Dr. Montalban.

The Results of Switching Treatments
If a neurologist decides that a change in therapy is advisable, one option is to switch from one first-line treatment to another. In a 2012 study, Río and colleagues found that patients who switched from an interferon to another interferon, from an interferon to glatiramer acetate, or from glatiramer acetate to an interferon had a decreased annualized relapse rate at 12 months.

A 2009 trial by Gajofatto and colleagues resulted in similar findings. Patients who switched from interferon beta or glatiramer acetate to natalizumab had greater reductions in annualized relapse rate at 24 months than participants who switched from one first-line therapy to another. In a similar study conducted in 2012, Prosperini and colleagues found no significant differences in disease activity at 12 months between patients switching from one first-line treatment to another and patients switching from a first-line to a second-line treatment. At 24 months freedom from disease activity was more common among patients who had escalated therapies than among patients who had switched between first-line treatments.

Few studies have examined the results of escalating to fingolimod, but their results generally have been positive. In a retrospective study, Bergvall and colleagues found a 59% reduction in the probability of having a relapse in patients who switched to fingolimod, compared with patients who switched to glatiramer acetate. In a 2011 extension of the TRANSFORMS trial, patients who had been treated with interferon beta-1a for one year were switched to fingolimod. These patients had a 50% reduction in annualized relapse rate after the switch, and the benefits were sustained for 4.5 years.

Considering Factors Beyond Clinical Efficacy
When neurologists consider switching a patient’s therapy because of clinical inefficacy, they must take other factors such as side effects, convenience, patient preferences, and cost into account, said Dr. Montalban. Disease severity, in terms of the numbers and volumes of gadolinium-enhancing and T2 lesions and the presence of oligoclonal bands, also should be considered. Apart from clinical activity, gender, age, the desire to become pregnant, comorbidities, and concomitant drugs may influence treatment decisions.

If a patient taking a first-line therapy has mild disease activity, it would be reasonable to consider switching him or her to another first-line therapy, to teriflunomide, or to dimethyl fumarate, said Dr. Montalban. But for a patient who has moderately severe disease activity despite treatment with a first- or second-line medicine, the neurologist might consider switching to a more potent drug such as natalizumab, fingolimod, or alemtuzumab.

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