Can We Offer More to Patients with Multiple Sclerosis?

European Neurological Review, 2015;10(2):139–47 DOI: http://doi.org/10.17925/ENR.2015.10.02.139

Abstract:

The recent approvals of both teriflunomide (Aubagio®) and alemtuzumab (Lemtrada®) have meant that substantially more can now be offered to patients with multiple sclerosis (MS). In clinical trials, teriflunomide has shown consistent efficacy across patients with early disease (TOPIC study, n=618) and in patients with relapsing forms of MS (TEMSO, n=1,088 and TOWER studies n=1,169). Teriflunomide 14 mg/day showed consistent efficacy in patients with varying levels of disease activity and is the only approved oral MS therapy that significantly delayed disability progression in two phase III clinical trials. The safety profile of teriflunomide now extends to 12 years and the data support its use as a platform agent in patients with relapsing MS (RMS). In other phase II and III clinical trials (CAMMS223, n=334, CARE-MS 1, n=581 and CARE-MS 2, n=840), alemtuzumab has demonstrated superior efficacy (clinical and magnetic resonance imaging [MRI]) than high-dose subcutaneous (s.c.) interferon beta (IFNβ-1a). It has also shown improvement in pre-existing disability compared with IFNβ-1a s.c. and sustained efficacy over 3–4 years despite no further therapy after the second administration in the majority of the patients. Alemtuzumab has a consistent, well-characterised safety profile, so adverse events can be identified and managed using a comprehensive safety monitoring and education programme. Both teriflunomide and alemtuzumab therefore have favourable benefit– risk profiles in patients with early and/or active RMS. Their efficacies constitute real advances in MS treatment and in regular clinical use are likely to effectively control disease and improve outcomes for many MS patients.
Keywords: Teriflunomide, alemtuzumab, efficacy, safety, multiple sclerosis, patient selection, treatment administration, treatment timing
Disclosure: Bart Van Wijmeersch has received research and travel grants and honoraria for multiple sclerosis expert advice and speakers fees from Bayer-Schering, Biogen, Genzyme-Sanofi, Merck-Serono, Novartis and Teva. Celia Oreja-Guevara has received advisory board and consulting honoraria from Bayer, Biogen, Genzyme-Sanofi, Merck-Serono, Novartis and Teva. Ron Milo has received research grants, travel funding, speaker’s honoraria or consultation fees from Bayer-Schering, Biogen Idec, Genzyme, Medison Pharma, Neopharm, Novartis, Merck-Serono and Teva.
Acknowledgments: Editorial assistance was provided by James Gilbart at Touch Medical Media, London and funded by Genzyme. This article reports the proceedings of a sponsored satellite symposium and as such has not been subject to the journal’s usual peer-review process.
Received: July 01, 2015 Accepted August 26, 2015
Correspondence: Ron Milo, Department of Neurology, Barzilai Medical Center, Ashkelon 78278, Israel E: rmilo@barzi.health.gov.il
Support: This article was supported by Genzyme (a Sanofi company).
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Despite the availability of disease-modifying therapies (DMTs) in multiple sclerosis (MS) for over 2 decades, substantial unmet treatment needs have remained. From the patient perspective, there is a need for better tolerability, quality of life (QoL) benefits and customised treatment approaches that are based on disease prognosis and individual patient needs and risk– benefit ratio. From the healthcare provider perspective, there is a need for treatment approaches that address individual prognosis, optimised treatment outcomes in an increasingly complex treatment landscape and ability to achieve new treatment goals.1–11 The recent approvals of the oral treatment teriflunomide (Aubagio®) and the intravenous (IV) monoclonal antibody (mAb) treatment alemtuzumab (Lemtrada®) in MS have markedly changed the options available to neurologists and their ability to achieve these goals. This review considers how teriflunomide and alemtuzumab can fit into current and future treatment approaches to MS as discussed at a satellite symposium and a plenary session that were convened at the 9th Controversies in Neurology meeting at Budapest, Hungary, in March 2015.

Teriflunomide – For Whom, When, How?

Teriflunomide is a once-daily oral therapy that was approved for the treatment of relapsing forms of MS by the US Food and Drug Administration (FDA) in September 2012 and by the EU Commission in Europe in August 2013. The mode of action of teriflunomide in MS is not fully understood but it is known to selectively and reversibly inhibit dihydroorotate reductase, a key mitochondrial enzyme involved in de novo pyrimidine synthesis, which is required for the proliferation of activated lymphocytes. This results in fewer B and T cells crossing the blood–brain barrier. Teriflunomide also reduces the ability of activated B and T cells to participate in the damaging immune attack on the central nervous system and has other modes of action.12 These actions are quite specific and preserve adaptive immunity to infectious pathogens, which is an advantage over some other immunomodulating agents used in MS.13,14 Teriflunomide is not cytotoxic and does not deplete lymphocytes, so can be described as an immunomodulatory agent.

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Keywords: Teriflunomide, alemtuzumab, efficacy, safety, multiple sclerosis, patient selection, treatment administration, treatment timing