Research Article| Volume 3, ISSUE 5, P607-619, September 2014

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Outcomes of switching directly to oral fingolimod from injectable therapies: Results of the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis


      • The phase 4 Evaluate Patient OutComes study was conducted in North America.
      • Patients switched directly from an injectable DMT to fingolimod without a washout.
      • Most self-reported outcomes significantly improved 6 months after the switch.
      • The EPOC study broadens knowledge of fingolimod use in a real-world scenario.



      The Evaluate Patient OutComes ( Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout.


      In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5 mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4.


      Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout.


      Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT.


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        • Agashivala N
        • Kim E.
        Cost-effectiveness of early initiation of fingolimod versus delayed initiation after 1 year of intramuscular interferon beta-1a in patients with multiple sclerosis.
        Clin Ther. 2012; 34: 1583-1590
        • Arnau RC
        • Meagher MW
        • Norris MP
        • Bramson R.
        Psychometric evaluation of the Beck Depression Inventory-II with primary care medical patients.
        Health Psychol. 2001; 20: 112-119
        • Atkinson MJ
        • Sinha A
        • Hass SL
        • Colman SS
        • Kumar RN
        • Brod M.
        • et al.
        Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease.
        Health Qual Life Outcomes. 2004; 2: 12
        • Bayas A.
        Improving adherence to injectable disease-modifying drugs in multiple sclerosis.
        Expert Opin Drug Deliv. 2013; 10: 285-287
        • Berk M
        • Ng F
        • Dodd S
        • Callaly T
        • Campbell S
        • Bernardo M.
        • et al.
        The validity of the CGI severity and improvement scales as measures of clinical effectiveness suitable for routine clinical use.
        J Eval Clin Pract. 2008; 14: 979-983
        • Brandes DW
        • Callender T
        • Lathi E
        • O’Leary S.
        A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events.
        Curr Med Res Opin. 2009; 25: 77-92
        • Brinkmann V
        • Billich A
        • Baumruker T
        • Heining P
        • Schmouder R
        • Francis G.
        • et al.
        Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis.
        Nat Rev Drug Discov. 2010; 9: 883-897
        • Buzzard KA
        • Broadley SA
        • Butzkueven H.
        What do effective treatments for multiple sclerosis tell us about the molecular mechanisms involved in pathogenesis?.
        Int J Mol Sci. 2012; 13: 12665-12709
        • Calabresi PA
        • Radue EW
        • Goodin D
        • Jeffery D
        • Rammohan KW
        • Reder AT.
        • et al.
        Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial.
        Lancet Neurol. 2014; 13: 545-556
        • Cascione M
        • Wynn D
        • Barbato LM
        • Pestreich L
        • Schofield L
        • McCague K.
        Randomized, open-label study to evaluate patient-reported outcomes with fingolimod after changing from prior disease-modifying therapy for relapsing multiple sclerosis: EPOC study rationale and design.
        J Med Econ. 2013; 16: 859-865
        • Cohen J
        • Barkhof F
        • Comi G
        • Hartung HP
        • Kappos L
        • Khatri B.
        • et al.
        Oral fingolimod (FTY720) treatment improves the performance of daily activities compared with intramuscular interferon α-1a: patient-reported indices for multiple sclerosis (PRIMUS)-activities results from a phase III study (TRANSFORMS).
        Neurology. 2010; 74: A543
        • Cohen JA Barkhof F
        • Comi G
        • Hartung H-P
        • Khatri BO
        • Montalban X.
        • et al.
        Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.
        N Engl J Med. 2010; 362: 402-415
        • Doward LC
        • McKenna SP
        • Meads DM
        • Twiss J
        • Eckert BJ.
        The development of patient-reported outcome indices for multiple sclerosis (PRIMUS).
        Mult Scler. 2009; 15: 1092-1102
      1. Francis G., Kappos L., O’Connor P., Collins W., Zhang-Auberson L., de Vera A., et al. Lymphocytes and fingolimod - temporal pattern and relationship with infections. 2010; P442: Poster presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, 13–16 October 2010, Gothenburg, Sweden

        • Hofmann M
        • Brinkmann V
        • Zerwes HG.
        FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs.
        Int Immunopharmacol. 2006; 6: 1902-1910
      2. ICH. ICH harmonised tripartite guidelines for good clinical practice E6(R1). In: Proceedings of the International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use, Geneva 〈〉 [accessed 27.02.14] 1996.

      3. ICH. In: Proceedings of the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) 〈〉 [27.02.14] 2013.

        • Janardhan V
        • Bakshi R.
        Quality of life in patients with multiple sclerosis: the impact of fatigue and depression.
        J Neurol Sci. 2002; 205: 51-58
        • Jenkinson C
        • Stewart-Brown S
        • Petersen S
        • Paice C.
        Assessment of the SF-36 version 2 in the United Kingdom.
        J Epidemiol Community Health. 1999; 53: 46-50
        • Jensen LH
        • Osterlind K
        • Rytter C.
        Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC.
        Lung Cancer. 2008; 62: 85-91
        • Kappos L
        • Radue EW
        • O’Connor P
        • Polman C
        • Hohlfeld R
        • Calabresi P.
        • et al.
        A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis.
        N Engl J Med. 2010; 362: 387-401
        • Kurtzke JF.
        Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • La Mantia L
        • Munari LM
        • Lovati R.
        Glatiramer acetate for multiple sclerosis.
        Cochrane Database Syst Rev. 2010; : CD004678
        • Lima AP
        • del Giglio A.
        Randomized crossover trial of intravenous 5-FU versus oral UFT both modulated by leucovorin: a one-centre experience.
        Eur J Cancer Care. 2005; 14: 151-154
        • Nikfar S
        • Rahimi R
        • Abdollahi M.
        A meta-analysis of the efficacy and tolerability of interferon-beta in multiple sclerosis, overall and by drug and disease type.
        Clin Ther. 2010; 32: 1871-1888
        • Oliver BJ
        • Kohli E
        • Kasper LH.
        Interferon therapy in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis of the comparative trials.
        J Neurol Sci. 2011; 302: 96-105
        • Osborne RH
        • De Abreu Lourenco R
        • Dalton A
        • Houltram J
        • Dowton D
        • Joshua DE.
        • et al.
        Quality of life related to oral versus subcutaneous iron chelation: a time trade-off study.
        Value Health J Int Soc Pharmacoecon Outcomes Res. 2007; 10: 451-456
        • Peidro-Garces L
        • Otero-Fernandez R
        • Lozano-Lizarraga L.
        [Adherence to and satisfaction with oral outpatient thromboembolism prophylaxis compared to parenteral: SALTO study].
        Rev Esp Cir Ortop Traumatol. 2013; 57: 53-60
        • Polman CH
        • Reingold SC
        • Edan G
        • Filippi M
        • Hartung HP
        • Kappos L.
        • et al.
        Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria".
        Ann Neurol. 2005; 58: 840-846
        • Qizilbash N
        • Mendez I
        • Sanchez-de la Rosa R.
        Benefit-risk analysis of glatiramer acetate for relapsing-remitting and clinically isolated syndrome multiple sclerosis.
        Clin Ther. 2012; 34 (, e5): 159-176
        • Rice GP
        • Incorvaia B
        • Munari L
        • Ebers G
        • Polman C
        • D’Amico R.
        • et al.
        Interferon in relapsing-remitting multiple sclerosis.
        Cochrane Database Syst Rev. 2001; : CD002002
        • Sospedra M
        • Martin R.
        Immunology of multiple sclerosis.
        Annu Rev Immunol. 2005; 23: 683-747
        • Tan H
        • Cai Q
        • Agarwal S
        • Stephenson JJ
        • Kamat S.
        Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis.
        Adv Ther. 2011; 28: 51-61
        • Treadaway K
        • Cutter G
        • Salter A
        • Lynch S
        • Simsarian J
        • Corboy J.
        • et al.
        Factors that influence adherence with disease-modifying therapy in MS.
        J Neurol. 2009; 256: 568-576
        • Treadaway K
        • Cutter G
        • Salter A
        • Lynch S
        • Simsarian J
        • Corboy J.
        • et al.
        Factors that influence adherence with disease-modifying therapy in MS.
        J Neurol. 2009; 256: 568-576
        • Twelves C
        • Gollins S
        • Grieve R
        • Samuel L.
        A randomised cross-over trial comparing patient preference for oral capecitabine and 5-fluorouracil/leucovorin regimens in patients with advanced colorectal cancer.
        Ann Oncol Off J Eur Soc Med Oncol / ESMO. 2006; 17: 239-245
      4. US prescribing information. Gilenya prescribing information. 〈〉 [accessed 03.14]2014.

        • Valko PO
        • Bassetti CL
        • Bloch KE
        • Held U
        • Baumann CR.
        Validation of the fatigue severity scale in a Swiss cohort.
        Sleep. 2008; 31: 1601-1607
        • Weinshenker BG
        • Bass B
        • Rice GP
        • Noseworthy J
        • Carriere W
        • Baskerville J.
        • et al.
        The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course.
        Brain. 1989; 112: 1419-1428
      5. World Medical Association. Declaration of Helsinki: Ethical principles for medical research involving human subjects. [27.02.14] 2014

        • Ziemssen T
        • Vollmar P
        • Meergans M
        • Tracik F
        • Diaz Lorente M
        • Neidhardt K.
        • et al.
        Interim results of the PANGAEA and PEARL studies, comparing treatment satisfaction and pharmaco-economic data of fingolimod (Gilenya®) and first-line therapies in multiple sclerosis patients in Germany.
        Neurology. 2013; 80 P03: 220

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