Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority
Identifieur interne : 000813 ( Pmc/Checkpoint ); précédent : 000812; suivant : 000814Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority
Auteurs : Silvia Romano [Italie] ; Michela Ferraldeschi [Italie] ; Francesca Bagnato [États-Unis] ; Rosella Mechelli [Italie] ; Emanuele Morena [Italie] ; Marzia Caldano [Italie] ; Maria Chiara Buscarinu [Italie] ; Arianna Fornasiero [Italie] ; Marco Frontoni [Italie] ; Viviana Nociti [Italie] ; Massimiliano Mirabella [Italie] ; Flavia Mayer [Italie] ; Antonio Bertolotto [Italie] ; Carlo Pozzilli [Italie] ; Nicola Vanacore [Italie] ; Marco Salvetti [Italie] ; Giovanni Ristori [Italie]Source :
- Frontiers in Neurology [ 1664-2295 ] ; 2019.
Abstract
Url:
DOI: 10.3389/fneur.2019.00695
PubMed: 31379701
PubMed Central: 6646514
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority</title><author><name sortKey="Romano, Silvia" sort="Romano, Silvia" uniqKey="Romano S" first="Silvia" last="Romano">Silvia Romano</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ferraldeschi, Michela" sort="Ferraldeschi, Michela" uniqKey="Ferraldeschi M" first="Michela" last="Ferraldeschi">Michela Ferraldeschi</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neurology and Psychiatry, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bagnato, Francesca" sort="Bagnato, Francesca" uniqKey="Bagnato F" first="Francesca" last="Bagnato">Francesca Bagnato</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Neuroimmunology Division, Department of Neurology, Neuroimaging Unit, Vanderbilt University Medical Centre</institution>,<addr-line>Nashville, TN</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mechelli, Rosella" sort="Mechelli, Rosella" uniqKey="Mechelli R" first="Rosella" last="Mechelli">Rosella Mechelli</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Morena, Emanuele" sort="Morena, Emanuele" uniqKey="Morena E" first="Emanuele" last="Morena">Emanuele Morena</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Caldano, Marzia" sort="Caldano, Marzia" uniqKey="Caldano M" first="Marzia" last="Caldano">Marzia Caldano</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Neurologia – Centro Riferimento Regionale Sclerosi Multipla and Neuroscience Institute Cavalieri Ottolenghi, San Luigi Hospital</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Buscarinu, Maria Chiara" sort="Buscarinu, Maria Chiara" uniqKey="Buscarinu M" first="Maria Chiara" last="Buscarinu">Maria Chiara Buscarinu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fornasiero, Arianna" sort="Fornasiero, Arianna" uniqKey="Fornasiero A" first="Arianna" last="Fornasiero">Arianna Fornasiero</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Frontoni, Marco" sort="Frontoni, Marco" uniqKey="Frontoni M" first="Marco" last="Frontoni">Marco Frontoni</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>D.A.I. Neurosciences and Mental Health, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nociti, Viviana" sort="Nociti, Viviana" uniqKey="Nociti V" first="Viviana" last="Nociti">Viviana Nociti</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Università Cattolica, Fondazione Policlinico Universitario “A. Gemelli</institution>,<addr-line>” Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Don Carlo Gnocchi Foundation Onlus</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mirabella, Massimiliano" sort="Mirabella, Massimiliano" uniqKey="Mirabella M" first="Massimiliano" last="Mirabella">Massimiliano Mirabella</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Università Cattolica, Fondazione Policlinico Universitario “A. Gemelli</institution>,<addr-line>” Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mayer, Flavia" sort="Mayer, Flavia" uniqKey="Mayer F" first="Flavia" last="Mayer">Flavia Mayer</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>National Centre of Epidemiology, National Institute of Health</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bertolotto, Antonio" sort="Bertolotto, Antonio" uniqKey="Bertolotto A" first="Antonio" last="Bertolotto">Antonio Bertolotto</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Neurologia – Centro Riferimento Regionale Sclerosi Multipla and Neuroscience Institute Cavalieri Ottolenghi, San Luigi Hospital</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pozzilli, Carlo" sort="Pozzilli, Carlo" uniqKey="Pozzilli C" first="Carlo" last="Pozzilli">Carlo Pozzilli</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neurology and Psychiatry, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vanacore, Nicola" sort="Vanacore, Nicola" uniqKey="Vanacore N" first="Nicola" last="Vanacore">Nicola Vanacore</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>National Centre of Epidemiology, National Institute of Health</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Salvetti, Marco" sort="Salvetti, Marco" uniqKey="Salvetti M" first="Marco" last="Salvetti">Marco Salvetti</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed</institution>,<addr-line>Pozzilli</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ristori, Giovanni" sort="Ristori, Giovanni" uniqKey="Ristori G" first="Giovanni" last="Ristori">Giovanni Ristori</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31379701</idno><idno type="pmc">6646514</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646514</idno><idno type="RBID">PMC:6646514</idno><idno type="doi">10.3389/fneur.2019.00695</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000556</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000556</idno><idno type="wicri:Area/Pmc/Curation">000556</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000556</idno><idno type="wicri:Area/Pmc/Checkpoint">000813</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000813</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority</title><author><name sortKey="Romano, Silvia" sort="Romano, Silvia" uniqKey="Romano S" first="Silvia" last="Romano">Silvia Romano</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ferraldeschi, Michela" sort="Ferraldeschi, Michela" uniqKey="Ferraldeschi M" first="Michela" last="Ferraldeschi">Michela Ferraldeschi</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neurology and Psychiatry, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bagnato, Francesca" sort="Bagnato, Francesca" uniqKey="Bagnato F" first="Francesca" last="Bagnato">Francesca Bagnato</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Neuroimmunology Division, Department of Neurology, Neuroimaging Unit, Vanderbilt University Medical Centre</institution>,<addr-line>Nashville, TN</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mechelli, Rosella" sort="Mechelli, Rosella" uniqKey="Mechelli R" first="Rosella" last="Mechelli">Rosella Mechelli</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Morena, Emanuele" sort="Morena, Emanuele" uniqKey="Morena E" first="Emanuele" last="Morena">Emanuele Morena</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Caldano, Marzia" sort="Caldano, Marzia" uniqKey="Caldano M" first="Marzia" last="Caldano">Marzia Caldano</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Neurologia – Centro Riferimento Regionale Sclerosi Multipla and Neuroscience Institute Cavalieri Ottolenghi, San Luigi Hospital</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Buscarinu, Maria Chiara" sort="Buscarinu, Maria Chiara" uniqKey="Buscarinu M" first="Maria Chiara" last="Buscarinu">Maria Chiara Buscarinu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fornasiero, Arianna" sort="Fornasiero, Arianna" uniqKey="Fornasiero A" first="Arianna" last="Fornasiero">Arianna Fornasiero</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Frontoni, Marco" sort="Frontoni, Marco" uniqKey="Frontoni M" first="Marco" last="Frontoni">Marco Frontoni</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>D.A.I. Neurosciences and Mental Health, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nociti, Viviana" sort="Nociti, Viviana" uniqKey="Nociti V" first="Viviana" last="Nociti">Viviana Nociti</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Università Cattolica, Fondazione Policlinico Universitario “A. Gemelli</institution>,<addr-line>” Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Don Carlo Gnocchi Foundation Onlus</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mirabella, Massimiliano" sort="Mirabella, Massimiliano" uniqKey="Mirabella M" first="Massimiliano" last="Mirabella">Massimiliano Mirabella</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Università Cattolica, Fondazione Policlinico Universitario “A. Gemelli</institution>,<addr-line>” Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mayer, Flavia" sort="Mayer, Flavia" uniqKey="Mayer F" first="Flavia" last="Mayer">Flavia Mayer</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>National Centre of Epidemiology, National Institute of Health</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bertolotto, Antonio" sort="Bertolotto, Antonio" uniqKey="Bertolotto A" first="Antonio" last="Bertolotto">Antonio Bertolotto</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Neurologia – Centro Riferimento Regionale Sclerosi Multipla and Neuroscience Institute Cavalieri Ottolenghi, San Luigi Hospital</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pozzilli, Carlo" sort="Pozzilli, Carlo" uniqKey="Pozzilli C" first="Carlo" last="Pozzilli">Carlo Pozzilli</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Neurology and Psychiatry, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vanacore, Nicola" sort="Vanacore, Nicola" uniqKey="Vanacore N" first="Nicola" last="Vanacore">Nicola Vanacore</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>National Centre of Epidemiology, National Institute of Health</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Salvetti, Marco" sort="Salvetti, Marco" uniqKey="Salvetti M" first="Marco" last="Salvetti">Marco Salvetti</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed</institution>,<addr-line>Pozzilli</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ristori, Giovanni" sort="Ristori, Giovanni" uniqKey="Ristori G" first="Giovanni" last="Ristori">Giovanni Ristori</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Neurology</title><idno type="eISSN">1664-2295</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Introduction:</bold> To compare a schedule with cyclic withdrawal (CW) of interferon beta (IFN-b) 1b, respect to the full regimen (FR), in relapsing-remitting MS (RR-MS).</p><p><bold>Methods:</bold> Participants were randomly assigned to CW or FR schedule and monthly monitored with brain MRI scans for 12 months (three of run-in and 9 of treatment). CW schedule included drug withdrawal for 1 month after two of treatment for a total of three quarters over the 9-month treatment period. The assessing neurologist and the expert neuroradiologists were blind. After the blind phase of the study all participants took their indicated disease modifying therapies in a prospectively planned, open-label extension phase (up to 120 months).</p><p><bold>Results:</bold> Of 60 randomized subjects 56 (29 in FR and 27 in CW group) completed the single-blind phase: the two groups were comparable, except for a non-significant difference in the number of contrast-enhanced lesions (CEL) at the end of run-in. The two-sided 90% CI for the ratio between median number of cumulative CEL was 0.29–1.07, allowing to significantly reject the null hypothesis of a ratio ≥1.2 and to meet the primary end-point of non-inferiority (the threshold and the ratio between median were chosen according to the non-normal distribution of the data). The differences (CW vs. FR) were also non-significant for secondary end points: mean cumulative number of T2-weighted new and enlarging lesions (3.48 ± 5.34 vs. 3.86 ± 6.76); mean number and volume (cm<sup>3</sup>) of black holes (1.24 ± 1.61 vs. 2.71 ± 4.56; 489.11 ± 1488.12 vs. 204.48 ± 396.98); number of patients with at least an active scan (21 vs. 22); mean relapse rate (0.52 ± 0.89 vs. 0.34 ± 0.66), relapse risk ratio adjusted for baseline variables (2.15 [0.64–7.18]), EDSS score (1.0 [1–1.56] vs. 1.5 [1–1.78]), proportion of patients with antibodies anti-IFN (5 [21%] vs. 8 [36%]). Fifty-four patients (27 for each study arm) completed the open-label phase. The annualized RR, EDSS, proportion of patients shifting to progressive disease and hazard ratio of shifting, adjusting for baseline covariates, were comparable between the two study groups.</p><p><bold>Conclusions:</bold> A calendar with CW was non-inferior than FR at the beginning of IFN-b therapy, and may not affect the long-term outcome.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://www.ClinicalTrials.gov">www.ClinicalTrials.gov</ext-link>, identifier: NCT00270816</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Thompson, Aj" uniqKey="Thompson A">AJ Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Metz, Lm" uniqKey="Metz L">LM Metz</name></author><author><name sortKey="Li, Dkb" uniqKey="Li D">DKB Li</name></author><author><name sortKey="Traboulsee, Al" uniqKey="Traboulsee A">AL Traboulsee</name></author><author><name sortKey="Duquette, P" uniqKey="Duquette P">P Duquette</name></author><author><name sortKey="Eliasziw, M" uniqKey="Eliasziw M">M Eliasziw</name></author><author><name sortKey="Cerchiaro, G" uniqKey="Cerchiaro G">G Cerchiaro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahad, Dh" uniqKey="Mahad D">DH Mahad</name></author><author><name sortKey="Trapp, Bd" uniqKey="Trapp B">BD Trapp</name></author><author><name sortKey="Lassmann, H" uniqKey="Lassmann H">H Lassmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salvetti, M" uniqKey="Salvetti M">M Salvetti</name></author><author><name sortKey="Landsman, D" uniqKey="Landsman D">D Landsman</name></author><author><name sortKey="Schwarz Lam, P" uniqKey="Schwarz Lam P">P Schwarz-Lam</name></author><author><name sortKey="Comi, G" uniqKey="Comi G">G Comi</name></author><author><name sortKey="Thompson, Aj" uniqKey="Thompson A">AJ Thompson</name></author><author><name sortKey="Fox, Rj" uniqKey="Fox R">RJ Fox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faissner, S" uniqKey="Faissner S">S Faissner</name></author><author><name sortKey="Mahjoub, Y" uniqKey="Mahjoub Y">Y Mahjoub</name></author><author><name sortKey="Mishra, M" uniqKey="Mishra M">M Mishra</name></author><author><name sortKey="Haupeltshofer, S" uniqKey="Haupeltshofer S">S Haupeltshofer</name></author><author><name sortKey="Hahn, Jn" uniqKey="Hahn J">JN Hahn</name></author><author><name sortKey="Gold, R" uniqKey="Gold R">R Gold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Annibali, V" uniqKey="Annibali V">V Annibali</name></author><author><name sortKey="Di Giovanni, S" uniqKey="Di Giovanni S">S Di Giovanni</name></author><author><name sortKey="Cannoni, S" uniqKey="Cannoni S">S Cannoni</name></author><author><name sortKey="Giugni, E" uniqKey="Giugni E">E Giugni</name></author><author><name sortKey="Bomprezzi, R" uniqKey="Bomprezzi R">R Bomprezzi</name></author><author><name sortKey="Mattei, C" uniqKey="Mattei C">C Mattei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald, Wi" uniqKey="Mcdonald W">WI McDonald</name></author><author><name sortKey="Compston, A" uniqKey="Compston A">A Compston</name></author><author><name sortKey="Edan, G" uniqKey="Edan G">G Edan</name></author><author><name sortKey="Goodkin, D" uniqKey="Goodkin D">D Goodkin</name></author><author><name sortKey="Hartung, Hp" uniqKey="Hartung H">HP Hartung</name></author><author><name sortKey="Lublin, Fd" uniqKey="Lublin F">FD Lublin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurtzke, Jf" uniqKey="Kurtzke J">JF Kurtzke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bagnato, F" uniqKey="Bagnato F">F Bagnato</name></author><author><name sortKey="Jeffries, N" uniqKey="Jeffries N">N Jeffries</name></author><author><name sortKey="Richert, Nd" uniqKey="Richert N">ND Richert</name></author><author><name sortKey="Stone, Rd" uniqKey="Stone R">RD Stone</name></author><author><name sortKey="Ohayon, Jm" uniqKey="Ohayon J">JM Ohayon</name></author><author><name sortKey="Mcfarland, Hf" uniqKey="Mcfarland H">HF McFarland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertolotto, A" uniqKey="Bertolotto A">A Bertolotto</name></author><author><name sortKey="Malucchi, S" uniqKey="Malucchi S">S Malucchi</name></author><author><name sortKey="Milano, E" uniqKey="Milano E">E Milano</name></author><author><name sortKey="Castello, A" uniqKey="Castello A">A Castello</name></author><author><name sortKey="Capobianco, M" uniqKey="Capobianco M">M Capobianco</name></author><author><name sortKey="Mutani, R" uniqKey="Mutani R">R Mutani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antonelli, G" uniqKey="Antonelli G">G Antonelli</name></author><author><name sortKey="Bagnato, F" uniqKey="Bagnato F">F Bagnato</name></author><author><name sortKey="Pozzilli, C" uniqKey="Pozzilli C">C Pozzilli</name></author><author><name sortKey="Simeoni, E" uniqKey="Simeoni E">E Simeoni</name></author><author><name sortKey="Bastianelli, S" uniqKey="Bastianelli S">S Bastianelli</name></author><author><name sortKey="Currenti, M" uniqKey="Currenti M">M Currenti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawade, Y" uniqKey="Kawade Y">Y Kawade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grossberg, Se" uniqKey="Grossberg S">SE Grossberg</name></author><author><name sortKey="Kawade, Y" uniqKey="Kawade Y">Y Kawade</name></author><author><name sortKey="Kohase, M" uniqKey="Kohase M">M Kohase</name></author><author><name sortKey="Klein, Jp" uniqKey="Klein J">JP Klein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lublin, Fd" uniqKey="Lublin F">FD Lublin</name></author><author><name sortKey="Reingold, Sc" uniqKey="Reingold S">SC Reingold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lublin, Fd" uniqKey="Lublin F">FD Lublin</name></author><author><name sortKey="Reingold, Sc" uniqKey="Reingold S">SC Reingold</name></author><author><name sortKey="Cohen, Ja" uniqKey="Cohen J">JA Cohen</name></author><author><name sortKey="Cutter, Gr" uniqKey="Cutter G">GR Cutter</name></author><author><name sortKey="S Rensen, Ps" uniqKey="S Rensen P">PS Sørensen</name></author><author><name sortKey="Thompson, Aj" uniqKey="Thompson A">AJ Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pozzilli, C" uniqKey="Pozzilli C">C Pozzilli</name></author><author><name sortKey="Bastianello, S" uniqKey="Bastianello S">S Bastianello</name></author><author><name sortKey="Koudriavtseva, T" uniqKey="Koudriavtseva T">T Koudriavtseva</name></author><author><name sortKey="Gasperini, C" uniqKey="Gasperini C">C Gasperini</name></author><author><name sortKey="Bozzao, A" uniqKey="Bozzao A">A Bozzao</name></author><author><name sortKey="Millefiorini, E" uniqKey="Millefiorini E">E Millefiorini</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Pocock, Sj" uniqKey="Pocock S">SJ Pocock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Green, Aj" uniqKey="Green A">AJ Green</name></author><author><name sortKey="Gelfand, Jm" uniqKey="Gelfand J">JM Gelfand</name></author><author><name sortKey="Cree, Ba" uniqKey="Cree B">BA Cree</name></author><author><name sortKey="Bevan, C" uniqKey="Bevan C">C Bevan</name></author><author><name sortKey="Boscardin, Wj" uniqKey="Boscardin W">WJ Boscardin</name></author><author><name sortKey="Mei, F" uniqKey="Mei F">F Mei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calabresi, Pa" uniqKey="Calabresi P">PA Calabresi</name></author><author><name sortKey="Kieseier, Bc" uniqKey="Kieseier B">BC Kieseier</name></author><author><name sortKey="Arnold, Dl" uniqKey="Arnold D">DL Arnold</name></author><author><name sortKey="Balcer, Lj" uniqKey="Balcer L">LJ Balcer</name></author><author><name sortKey="Boyko, A" uniqKey="Boyko A">A Boyko</name></author><author><name sortKey="Pelletier, J" uniqKey="Pelletier J">J Pelletier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwid, Sr" uniqKey="Schwid S">SR Schwid</name></author><author><name sortKey="Panitch, Hs" uniqKey="Panitch H">HS Panitch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Di Rezze, S" uniqKey="Di Rezze S">S Di Rezze</name></author><author><name sortKey="Gupta, S" uniqKey="Gupta S">S Gupta</name></author><author><name sortKey="Durastanti, V" uniqKey="Durastanti V">V Durastanti</name></author><author><name sortKey="Millefiorini, E" uniqKey="Millefiorini E">E Millefiorini</name></author><author><name sortKey="Pozzilli, C" uniqKey="Pozzilli C">C Pozzilli</name></author><author><name sortKey="Bagnato, F" uniqKey="Bagnato F">F Bagnato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hartung, Hp" uniqKey="Hartung H">HP Hartung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prosperini, L" uniqKey="Prosperini L">L Prosperini</name></author><author><name sortKey="Borriello, G" uniqKey="Borriello G">G Borriello</name></author><author><name sortKey="De Giglio, L" uniqKey="De Giglio L">L De Giglio</name></author><author><name sortKey="Leonardi, L" uniqKey="Leonardi L">L Leonardi</name></author><author><name sortKey="Barletta, V" uniqKey="Barletta V">V Barletta</name></author><author><name sortKey="Pozzilli, C" uniqKey="Pozzilli C">C Pozzilli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snell, Lm" uniqKey="Snell L">LM Snell</name></author><author><name sortKey="Mcgaha, Tl" uniqKey="Mcgaha T">TL McGaha</name></author><author><name sortKey="Brooks, Dg" uniqKey="Brooks D">DG Brooks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Negro, F" uniqKey="Negro F">F Negro</name></author><author><name sortKey="Baldi, M" uniqKey="Baldi M">M Baldi</name></author><author><name sortKey="Mondardini, A" uniqKey="Mondardini A">A Mondardini</name></author><author><name sortKey="Leandro, G" uniqKey="Leandro G">G Leandro</name></author><author><name sortKey="Chaneac, M" uniqKey="Chaneac M">M Chaneac</name></author><author><name sortKey="Manzini, P" uniqKey="Manzini P">P Manzini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, M" uniqKey="Tanaka M">M Tanaka</name></author><author><name sortKey="Kinoshita, M" uniqKey="Kinoshita M">M Kinoshita</name></author><author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, K" uniqKey="Takahashi K">K Takahashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Killestein, J" uniqKey="Killestein J">J Killestein</name></author><author><name sortKey="Vennegoor, A" uniqKey="Vennegoor A">A Vennegoor</name></author><author><name sortKey="Strijbis, Em" uniqKey="Strijbis E">EM Strijbis</name></author><author><name sortKey="Seewann, A" uniqKey="Seewann A">A Seewann</name></author><author><name sortKey="Van Oosten, Bw" uniqKey="Van Oosten B">BW van Oosten</name></author><author><name sortKey="Uitdehaag, Bm" uniqKey="Uitdehaag B">BM Uitdehaag</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mauri, L" uniqKey="Mauri L">L Mauri</name></author><author><name sortKey="D Agostino, Rb" uniqKey="D Agostino R">RB D'Agostino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trojano, M" uniqKey="Trojano M">M Trojano</name></author><author><name sortKey="Pellegrini, F" uniqKey="Pellegrini F">F Pellegrini</name></author><author><name sortKey="Fuiani, A" uniqKey="Fuiani A">A Fuiani</name></author><author><name sortKey="Paolicelli, D" uniqKey="Paolicelli D">D Paolicelli</name></author><author><name sortKey="Zipoli, V" uniqKey="Zipoli V">V Zipoli</name></author><author><name sortKey="Zimatore, Gb" uniqKey="Zimatore G">GB Zimatore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Freedman, Ms" uniqKey="Freedman M">MS Freedman</name></author><author><name sortKey="Wolinsky, Js" uniqKey="Wolinsky J">JS Wolinsky</name></author><author><name sortKey="Wamil, B" uniqKey="Wamil B">B Wamil</name></author><author><name sortKey="Confavreux, C" uniqKey="Confavreux C">C Confavreux</name></author><author><name sortKey="Comi, G" uniqKey="Comi G">G Comi</name></author><author><name sortKey="Kappos, L" uniqKey="Kappos L">L Kappos</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Neurol</journal-id><journal-id journal-id-type="iso-abbrev">Front Neurol</journal-id><journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id><journal-title-group><journal-title>Frontiers in Neurology</journal-title></journal-title-group><issn pub-type="epub">1664-2295</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31379701</article-id><article-id pub-id-type="pmc">6646514</article-id><article-id pub-id-type="doi">10.3389/fneur.2019.00695</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neurology</subject><subj-group><subject>Clinical Trial</subject></subj-group></subj-group></article-categories><title-group><article-title>Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Romano</surname><given-names>Silvia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn002"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/290825/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Ferraldeschi</surname><given-names>Michela</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn002"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/680188/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Bagnato</surname><given-names>Francesca</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mechelli</surname><given-names>Rosella</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/621817/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Morena</surname><given-names>Emanuele</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Caldano</surname><given-names>Marzia</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/532353/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Buscarinu</surname><given-names>Maria Chiara</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fornasiero</surname><given-names>Arianna</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/681107/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Frontoni</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/747485/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Nociti</surname><given-names>Viviana</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mirabella</surname><given-names>Massimiliano</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/693991/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Mayer</surname><given-names>Flavia</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/755023/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Bertolotto</surname><given-names>Antonio</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pozzilli</surname><given-names>Carlo</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/739356/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Vanacore</surname><given-names>Nicola</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/23542/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Salvetti</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff9"><sup>9</sup></xref><xref ref-type="corresp" rid="c001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/157693/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Ristori</surname><given-names>Giovanni</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="c002"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/620841/overview"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, Center for Experimental Neurological Therapies, S. Andrea Hospital-site, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></aff><aff id="aff2"><sup>2</sup><institution>Department of Neurology and Psychiatry, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></aff><aff id="aff3"><sup>3</sup><institution>Neuroimmunology Division, Department of Neurology, Neuroimaging Unit, Vanderbilt University Medical Centre</institution>,<addr-line>Nashville, TN</addr-line>,<country>United States</country></aff><aff id="aff4"><sup>4</sup><institution>Neurologia – Centro Riferimento Regionale Sclerosi Multipla and Neuroscience Institute Cavalieri Ottolenghi, San Luigi Hospital</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></aff><aff id="aff5"><sup>5</sup><institution>D.A.I. Neurosciences and Mental Health, “Sapienza” University of Rome</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></aff><aff id="aff6"><sup>6</sup><institution>Università Cattolica, Fondazione Policlinico Universitario “A. Gemelli</institution>,<addr-line>” Rome</addr-line>,<country>Italy</country></aff><aff id="aff7"><sup>7</sup><institution>Don Carlo Gnocchi Foundation Onlus</institution>,<addr-line>Milan</addr-line>,<country>Italy</country></aff><aff id="aff8"><sup>8</sup><institution>National Centre of Epidemiology, National Institute of Health</institution>,<addr-line>Rome</addr-line>,<country>Italy</country></aff><aff id="aff9"><sup>9</sup><institution>IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed</institution>,<addr-line>Pozzilli</addr-line>,<country>Italy</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Hans-Peter Hartung, Heinrich Heine University of Düsseldorf, Germany</p></fn><fn fn-type="edited-by"><p>Reviewed by: Maria José Sá, Centro Hospitalar São João, Portugal; Eva Havrdova, Charles University in Prague, Czechia</p></fn><corresp id="c001">*Correspondence: Marco Salvetti <email>marco.salvetti@uniroma1.it</email></corresp><corresp id="c002">Giovanni Ristori <email>giovanni.ristori@uniroma1.it</email></corresp><fn fn-type="other" id="fn001"><p>This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology</p></fn><fn fn-type="other" id="fn002"><p>†These authors have contributed equally to this work</p></fn></author-notes><pub-date pub-type="epub"><day>16</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>695</elocation-id><history><date date-type="received"><day>13</day><month>2</month><year>2019</year></date><date date-type="accepted"><day>13</day><month>6</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Romano, Ferraldeschi, Bagnato, Mechelli, Morena, Caldano, Buscarinu, Fornasiero, Frontoni, Nociti, Mirabella, Mayer, Bertolotto, Pozzilli, Vanacore, Salvetti and Ristori.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Romano, Ferraldeschi, Bagnato, Mechelli, Morena, Caldano, Buscarinu, Fornasiero, Frontoni, Nociti, Mirabella, Mayer, Bertolotto, Pozzilli, Vanacore, Salvetti and Ristori</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p><bold>Introduction:</bold> To compare a schedule with cyclic withdrawal (CW) of interferon beta (IFN-b) 1b, respect to the full regimen (FR), in relapsing-remitting MS (RR-MS).</p><p><bold>Methods:</bold> Participants were randomly assigned to CW or FR schedule and monthly monitored with brain MRI scans for 12 months (three of run-in and 9 of treatment). CW schedule included drug withdrawal for 1 month after two of treatment for a total of three quarters over the 9-month treatment period. The assessing neurologist and the expert neuroradiologists were blind. After the blind phase of the study all participants took their indicated disease modifying therapies in a prospectively planned, open-label extension phase (up to 120 months).</p><p><bold>Results:</bold> Of 60 randomized subjects 56 (29 in FR and 27 in CW group) completed the single-blind phase: the two groups were comparable, except for a non-significant difference in the number of contrast-enhanced lesions (CEL) at the end of run-in. The two-sided 90% CI for the ratio between median number of cumulative CEL was 0.29–1.07, allowing to significantly reject the null hypothesis of a ratio ≥1.2 and to meet the primary end-point of non-inferiority (the threshold and the ratio between median were chosen according to the non-normal distribution of the data). The differences (CW vs. FR) were also non-significant for secondary end points: mean cumulative number of T2-weighted new and enlarging lesions (3.48 ± 5.34 vs. 3.86 ± 6.76); mean number and volume (cm<sup>3</sup>) of black holes (1.24 ± 1.61 vs. 2.71 ± 4.56; 489.11 ± 1488.12 vs. 204.48 ± 396.98); number of patients with at least an active scan (21 vs. 22); mean relapse rate (0.52 ± 0.89 vs. 0.34 ± 0.66), relapse risk ratio adjusted for baseline variables (2.15 [0.64–7.18]), EDSS score (1.0 [1–1.56] vs. 1.5 [1–1.78]), proportion of patients with antibodies anti-IFN (5 [21%] vs. 8 [36%]). Fifty-four patients (27 for each study arm) completed the open-label phase. The annualized RR, EDSS, proportion of patients shifting to progressive disease and hazard ratio of shifting, adjusting for baseline covariates, were comparable between the two study groups.</p><p><bold>Conclusions:</bold> A calendar with CW was non-inferior than FR at the beginning of IFN-b therapy, and may not affect the long-term outcome.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://www.ClinicalTrials.gov">www.ClinicalTrials.gov</ext-link>, identifier: NCT00270816</p></abstract><kwd-group><kwd>relapsing-remitting multiple sclerosis</kwd><kwd>interferon beta 1b</kwd><kwd>non-inferiority</kwd><kwd>cyclic withdrawal</kwd><kwd>contrast-enhanced lesions</kwd><kwd>black holes</kwd></kwd-group><counts><fig-count count="2"></fig-count><table-count count="3"></table-count><equation-count count="0"></equation-count><ref-count count="32"></ref-count><page-count count="9"></page-count><word-count count="6274"></word-count></counts></article-meta></front></pmc><affiliations><list><country><li>Italie</li><li>États-Unis</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Romano, Silvia" sort="Romano, Silvia" uniqKey="Romano S" first="Silvia" last="Romano">Silvia Romano</name></noRegion><name sortKey="Bertolotto, Antonio" sort="Bertolotto, Antonio" uniqKey="Bertolotto A" first="Antonio" last="Bertolotto">Antonio Bertolotto</name><name sortKey="Buscarinu, Maria Chiara" sort="Buscarinu, Maria Chiara" uniqKey="Buscarinu M" first="Maria Chiara" last="Buscarinu">Maria Chiara Buscarinu</name><name sortKey="Caldano, Marzia" sort="Caldano, Marzia" uniqKey="Caldano M" first="Marzia" last="Caldano">Marzia Caldano</name><name sortKey="Ferraldeschi, Michela" sort="Ferraldeschi, Michela" uniqKey="Ferraldeschi M" first="Michela" last="Ferraldeschi">Michela Ferraldeschi</name><name sortKey="Fornasiero, Arianna" sort="Fornasiero, Arianna" uniqKey="Fornasiero A" first="Arianna" last="Fornasiero">Arianna Fornasiero</name><name sortKey="Frontoni, Marco" sort="Frontoni, Marco" uniqKey="Frontoni M" first="Marco" last="Frontoni">Marco Frontoni</name><name sortKey="Mayer, Flavia" sort="Mayer, Flavia" uniqKey="Mayer F" first="Flavia" last="Mayer">Flavia Mayer</name><name sortKey="Mechelli, Rosella" sort="Mechelli, Rosella" uniqKey="Mechelli R" first="Rosella" last="Mechelli">Rosella Mechelli</name><name sortKey="Mirabella, Massimiliano" sort="Mirabella, Massimiliano" uniqKey="Mirabella M" first="Massimiliano" last="Mirabella">Massimiliano Mirabella</name><name sortKey="Morena, Emanuele" sort="Morena, Emanuele" uniqKey="Morena E" first="Emanuele" last="Morena">Emanuele Morena</name><name sortKey="Nociti, Viviana" sort="Nociti, Viviana" uniqKey="Nociti V" first="Viviana" last="Nociti">Viviana Nociti</name><name sortKey="Nociti, Viviana" sort="Nociti, Viviana" uniqKey="Nociti V" first="Viviana" last="Nociti">Viviana Nociti</name><name sortKey="Pozzilli, Carlo" sort="Pozzilli, Carlo" uniqKey="Pozzilli C" first="Carlo" last="Pozzilli">Carlo Pozzilli</name><name sortKey="Ristori, Giovanni" sort="Ristori, Giovanni" uniqKey="Ristori G" first="Giovanni" last="Ristori">Giovanni Ristori</name><name sortKey="Salvetti, Marco" sort="Salvetti, Marco" uniqKey="Salvetti M" first="Marco" last="Salvetti">Marco Salvetti</name><name sortKey="Salvetti, Marco" sort="Salvetti, Marco" uniqKey="Salvetti M" first="Marco" last="Salvetti">Marco Salvetti</name><name sortKey="Vanacore, Nicola" sort="Vanacore, Nicola" uniqKey="Vanacore N" first="Nicola" last="Vanacore">Nicola Vanacore</name></country><country name="États-Unis"><noRegion><name sortKey="Bagnato, Francesca" sort="Bagnato, Francesca" uniqKey="Bagnato F" first="Francesca" last="Bagnato">Francesca Bagnato</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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