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`New treatment options encourage a fresh approach to patients.
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`A Q&A WITH JOHN CORBOY, MD, FAAN AND PATRICIA COYLE, MD, FAAN
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`fter years of status quo, the treatment landscape for
`multiple sclerosis has rapidly and undeniably changed.
`The grOWth of the field of MS therapies—now with
`three oral therapies on the market—creates new deci-
`sions for physicians and patients when it comes to treatment
`selection. While the influence of factors like insurance coverage
`and therapy cost should be minimal, according to the National
`Clinical Advisory Board of the National Multiple Sclerosis
`Society (See Sidebar) and many other experts, the reality of
`these bctors is inescapable in actual practice.
`To get a better sense of the decision-making process for spe—
`cialists, we asked MS experts to share thoughts on their current
`strategies for patient management.
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`Q. The field of diseasermodifying therapies has certainly
`grown in recent months. Could you briefly describe your
`general approach to treatment selection for the newly diag—
`nosed, treatment-naive patient with MS or suspected MS?
`John R. Corboy, MD, FAAN: Take no prisoners. Treat aggres-
`sively from the outset, so as to maximize reduction in inflam—
`matory disease activity.
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`Exceptions might be patients diagnosed after a long benign
`course, who likely will do well no matter what we treat them
`with (maybe even with nothing).
`Patricia K. Coyle, MD. FAAN: Drug selection is based on
`drug, disease. and patient faCtors, influenced by practical avail—
`ability and personal experience. I briefly discuss all options, then
`narrow down to recommend specific choices and their pros
`and cons,
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`Q: In the new treatment environment, how do you
`approach the established patient who is already on a
`therapy?
`Dr. Carboy If the patient is stable for a significant period of
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`time on whatever drug and tolerating it well, I leave them on
`that drug I have a very low threshold to move to best available
`therapy.
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`'Q. What factors do you believe justify considering a thera-
`peutic switch?
`Dr. Coyle. Any relapse while on therapy should be inveSti-
`gated for possible switch. Worsening on exam or surveillance
`MRI, in the setting of someone who feels well and reports no
`change, should be verified with alternative testing or lead to a
`second unacceptable MRI before switching on neuroimaging
`criteria alone.
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`Dr. Corboy: I look for new disease activity on scan or exam
`(i.e., attack or change in £055), or intolerance, especially if it
`affecrs compliance.
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`Q. is patient interest in oral therapy sufficient reason to
`initiate an oral agent over an injectable DMT?
`Dr. Corboy. if patients have been putting up with the pain
`and inconvenience of injeCtions for a period of time, and devel.
`Oping "shat burnout," switching to a more effeCtive drug that
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`i -FDR—AFPRoi/ép—M'sbisfisegmoorFriniElHEIiAmesfia
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`- Aubagio (teriflunomide)
`- Avonex (interferon beta‘ia)
`- Betaseron (interferon beta-1b)
`- Copaxone (glatiramer acetate)
`- Extavia (interferon beta-1b)
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`- Gilenya (fingolimod)
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`- Novantrone (mitoxantrone)
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`- Rebif (interferon beta-1a)
`- Tecfidera (dimethyl fumarate)
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`- Tysabri (natalizumab)
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`happens to be oral makes very good sense, from a compliance
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`and patient satisfaction point of view.
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`“'Rimrntorgm NMSS.0RG
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`COVER FOCUS
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`Q, What factors (insurance coverage/costs, convenience,
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`trial data, experience) would you say are most relevant to
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`you in your therapeutic decision-making?
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`Dr. Coyle: Trial data and experience are most important to
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`me. It is a sad commentary when cost/coverage becomes the
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`deciding factor.
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`Dr. Corboy: Efficacy. Efficacy. Risk. Compliance (convenience
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`and side effects). Insurance/costs never play a role in philo-
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`sophical choice, but often play a practical role in what we can
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`actually get for the patient.
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`Q: The media, patient groups, drug marketers, and even
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`neurologists sometimes seem to view the available therapies
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`according to their delivery method—injectable versus oral.
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`Do you think this is a meaningful distinction, or, more impor-
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`tantly, how would you recommend that your colleagues
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`treating MS conceptualize the field?
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`Dr. Corboy: To paraphrase James Carville, "It's the effi—
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`cacy, stupid." When you explain to patients that the goal
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`is to maintain their neurological function at their present
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`state for as long as possible, they clearly agree that is most
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`important. If you waffle around, talking about number of
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`injections per week, oral vs. injectable vs. infusion, the dis—
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`cussion is way off track.
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`Dr. Coyle: I think this is a meaningful distinCtion. I think of
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`MS options in three buckets: first line parenterals, second line
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`parenterals, and oral options.
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`Q. Several agents are new or relatively new to market.
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`What are you looking to learn about newer agents as experi—
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`Dr. Coyle: Over time I am looking at long—term efficacy and
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`safety, and that there are no late surprises. Over time, a sense of
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`the true tolerability and effectiveness of a new agent compared
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`to interferons and glatiramer acetate will become apparent.
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`Dr. Corboy: What is the true side effect profile, are there
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`longvterm risk issues? Does the efficacy remain intact over time?
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`How can we manage the risk?
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`Q. Can We still learn more about the interferons or glat’
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`iramer acetate in light of these new therapies?
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`Dr. Corboy: Although there is a general perception, and
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`some data that the "old" drugs are inferior, we likely still need
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`some comparative trials. It is, however, getting very difficult to
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`convince people to enter trials with injectables as the compara—
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`tor. I would favor trials comparing the higher efficacy medica—
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`tions to each other. This will never be sponsored by pharma,
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`and needs alternative techniques to accomplish.
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`Page 2 of 2
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`- Patients’ access to medication should n0t be limited by the
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`frequency of relapses, age, or level of disability.
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`- Treatment is not to be stopped while insurers evaluate for
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`continuing coverage of treatment, as this would put patients
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`at increased risk for recurrent disease activity.
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`- Therapy is to be continued indefinitely. except for the fol.
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`lowing circumstances: there is clear lack of benefit; there are
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`intolerable side effects; better therapy becomes available.
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`- All of these FDA-approved agents should be included in
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`formularies and covered by third party payers so that physi—
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`cians and patients can determine the most appropriate
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`agent on an individual basis; failure to do so is unethical and
`discriminatory.
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`- Movement from one disease-modifying medication to
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`another should occur only for medically appropriate reasons.
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`- None of the therapies has been approved for use by women
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`who are trying to become pregnant, are pregnant, or are
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`nursing mothers.
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`— National Clinical Advisory Board of the
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`National Multiple Sclerosis Society (2008)
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`Q. When does it make sense to discontinue medication?
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`How can the neurology community develop a consensus
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`Dr. Corboy l consider discontinuation of DMTs under the
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`following circumstances
`1. Intolerance
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`2. In a patient with apparent diminished risk of new inflam—
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`matory disease aCtivity
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`a. "Benign MS," likely around 60, with onset at least 15-20
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`years prior, no attack in the last five years, no enhancing MRI
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`lesion for S-plus years, and on DMT for at least 5-10 years, or
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`b. Same as above, but has more significant disability, but
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`appears to have “burned out," or
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`c. SPMS, with similar characteristics as above (i.e. age, dura—
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`tion of disease, no new lesions, no attacks, etc.)
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`We need a study to give us some guidance. Anyone who
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`says they know what to do in these contexts is making it up.
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`Data trumps all. E
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`john R. Carboy, MD, FAAN is Professor, Neurology, University
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`of Colorado School ofMedicine and Co-Director, Rocky Mountain
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`MS Center at Anschutz Medical Campus.
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`Patricia K. Coy/e, MD, FAAN is Professor and Vice Chair
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`(Clinical Afiairs), Department of Neurology, Stony Brook
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`University in Stony Brook, NY.
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`JULY/AUGUST 2013
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