Multiple Sclerosis Journal

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Jan 9, 2013 - every few days is a nuisance, particularly if there is an equi- potent oral therapy without significant safety problems. So what is the problem ...
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In the coming year we should abandon interferons and glatiramer acetate as first line therapy for MS: Commentary Michael Hutchinson Mult Scler 2013 19: 29 DOI: 10.1177/1352458512470507 The online version of this article can be found at: http://msj.sagepub.com/content/19/1/29

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470507 2012

MSJ19110.1177/1352458512470507Multiple Sclerosis JournalHutchinson

MULTIPLE SCLEROSIS MSJ JOURNAL

Controversies in Multiple Sclerosis

In the coming year we should abandon interferons and glatiramer acetate as first line therapy for MS: Commentary

Multiple Sclerosis Journal 19(1) 29­–30 © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458512470507 msj.sagepub.com

Michael Hutchinson

Yes it is good news that a range of oral disease modifying therapies (DMTs) will become available in 2013 and onward for patients with relapsing remitting multiple sclerosis (RRMS). The evidence, that some of the oral therapies are as equally effective as established first line DMTs (and by a number of MRI measures, more effective), increases the treatment options available to patients and neurologists. The good news for health care providers is that these newcomers and a range of biosimilars will pressure the big pharmaceutical companies manufacturing injectables (Biogen-Idec, Bayer-Schering, Merck-Serono and Teva) to reduce the prices of their products. For too long health insurance and state providers have been paying around €15,000 plus per annum for modestly effective therapies. Market forces should come into play and make these drugs more affordable. For the person with MS, clearly injecting every day or every few days is a nuisance, particularly if there is an equipotent oral therapy without significant safety problems. So what is the problem about changing to new oral therapies? Well, there are a number of problems:

If it ain’t broke don’t fix it If you, the person with MS, are feeling well on a first line injectable DMT, without any evidence of disease activity in the last few years (no relapses, EDSS stable, no MRI change), why would you change your treatment regime? All neurologists have patients with mild inflammatory disease well controlled on injectables over many years. If such patients ask in the clinic to change to a new oral therapy, then I, for one, will be reluctant to go with pure patient preference. We now have the evidence (denied by some for many years) that early treatment with injectables has longterm efficacy in reducing long-term hard end-points; the remarkable study by Doug Goodin of the long-term followup of the pivotal IFNB-1b study is an example.1

Increased efficacy and tolerability but at what cost? Importantly the institutions paying for this medication will certainly have an opinion. Why allow a patient to change to

a medication, which will undoubtedly cost much more than first-line DMTs, just because it is more convenient to administer? In recessionary times both private and state health providers need adequate reasons to change to a more expensive therapy. Convenience is not an adequate reason.

Are the new oral therapies that good/safe/tolerable? Present first-line DMTs have an excellent safety record. Comparisons without head-to head studies are invidious; we can only rely on what is published. There is caution about safety with fingolimod, with an amended start-up regime; that is why in Europe it is a second line therapy.2,3 Teriflunomide may be teratogenic, a considerable factor when treating women of child-bearing age4; we know that is not the case with injectables. BG-12 has problems with flushing and gastrointestinal symptoms in a small percentage (10%) of patients (admittedly side-effects improve with time).5 Laquinimod appears to have less anti-inflammatory effect (relapse reduction & MRI measures) than other oral therapies and less than first line DMTs.6 We should be cautious in advocating transfer to an oral therapy in patients presently well controlled on a first-line DMT.

Price may be a determinant of market penetration Phase III studies are expensive, as is the basic laboratory research in drug development; a pivotal study costs $3 billion to bring to fruition. Clearly pharmaceutical companies need to make profits and thus new DMTs are increasingly expensive. One might anticipate that in order to improve or maintain market penetration there will be significant reductions of the price of both older therapies and the newer oral drugs. That is the good news for consumers. Corresponding author: Michael Hutchinson, Consultant Neurologist, St Vincent’s University Hospital Newman Clinical Research Professor, University College Dublin Dublin, Ireland. Email: [email protected]

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Multiple Sclerosis Journal 19(1)

Disclosures Michael Hutchinson serves on a medical advisory board for the CONFIRM study [BG00012] for Biogen-Idec, serves on the editorial board of the Multiple Sclerosis journal, has received speaker’s honoraria from Novartis, Biogen-Idec and Bayer-Schering and receives research support from Dystonia Ireland and the Health Research Board of Ireland.

References 1. Goodin DS, Reder AT, Ebers GC, et al. Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. Neurology 2012; 78: 1315–1322.

2. Espinosa PS and Berger JR. Delayed fingolimod-associated asystole. Mult Scler 2011; 17: 1387–1389. 3. Bourdette D and Gilden D. Fingolimod and multiple sclerosis: Four cautionary tales. Neurology 2012; 79: 1942–1943. 4. O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011; 365: 1293–1303. 5. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 36: 1087–1097. 6. Comi G, Jeffery D, Kappos L, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 2012; 366: 1000–1009.

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