title: Oral contraceptives combined with interferon β in multiple sclerosis.
abstract: OBJECTIVE
  To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures.
  
  
  RESULTS
  The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81-1.14) in group 1, 0.84 (95% CI 0.66-1.02) in group 2, and 0.72 (95% CI 0.53-0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-β or OC discontinuations were equally distributed across groups.
  
  
  CONCLUSIONS
  Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research.
  
  
  METHODS
  This study provides Class II evidence that in women with RRMS, IFN-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone.
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Giglio
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Valeria T
authors.initials: VT
authors.lastname: Barletta
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marinelli
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Floriana De
authors.initials: FD
authors.lastname: Angelis
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Pagano
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Piattella
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tomassini
authors.affiliation: Department of Neurology and Psychiatry (C.P., L.D.G., F.D.A., M.C.P., V.T., P.P.), Sapienza University of Rome, Italy; MS Center (C.P., L.D.G., V.T.B., F.M.), S. Andrea Hospital, Sapienza University of Rome, Italy; Centre for Primary Care and Public Health (V.G.), Queen Mary University of London, UK; TFS Trial Form Support S.L. (V.A.P., S.M.), Rome, Italy; Institute of Psychological Medicine and Clinical Neurosciences (V.T.), Cardiff University School of Medicine University Hospital of Wales (V.T.), Cardiff, UK; Santa Lucia Foundation (V.T.), Rome, Italy; and IRCCS Neuromed (P.P.), Pozzilli (IS), Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pantano