title: Effect on Cognition of Estroprogestins Combined with Interferon Beta in Multiple Sclerosis: Analysis of Secondary Outcomes from a Randomised Controlled Trial.
abstract: BACKGROUND
  Cognitive impairment is a disabling symptom in multiple sclerosis (MS). While its management remains challenging, beneficial effects on cognition of interferon beta (IFN-β) have been reported and a positive effect from estroprogestins has been hypothesised, suggesting that the combination of the two medications in women with MS could offer a promising treatment strategy.
  
  
  OBJECTIVE
  We investigated whether a combination of estroprogestins and IFN-β can improve cognition in women with MS.
  
  
  METHODS
  Women with relapsing-remitting (RR) MS were randomly assigned (1:1:1) to receive subcutaneous IFN-β-1a (Rebif®, Merck Serono, Geneva, Switzerland) 44 mcg three times a week (tiw) (group 1), subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 20 mcg and desogestrel 150 mcg (Mercilon®, MSD Italia SRL, Rome, Italy) (group 2) or subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 40 mcg and desogestrel 125 mcg (Gracial®, Organon Italia S.p.A., Rome, Italy) (group 3) in a randomised controlled trial, for which we report the analysis of secondary outcomes. At baseline and at 24 months, all patients underwent magnetic resonance imaging (MRI) and a comprehensive cognitive assessment, including Rao's Brief Repeatable Battery (RBRB) and questionnaires for depression, fatigue and quality of life. Failure in at least two of the RBRB tests defined 'cognitive impairment'.
  
  
  RESULTS
  At baseline, there was no difference in the proportion of cognitively impaired patients. At month 24, the proportion of patients with cognitive impairment was lower in group 3 (34.8%) than in group 1 (47.6%) (p = 0.03). The risk of developing cognitive impairment over 24 months was lower in group 3 (p = 0.02). Mood and fatigue scores were comparable across the groups over time at both time points. However, at month 24, group 3 showed worsening on the sexual function subscale of the 54-item MS quality-of-life questionnaire (p = 0.03).
  
  
  CONCLUSIONS
  This study suggests that the combination of high-dose estroprogestins and IFN-β may have positive effects on cognition. However, the effect of this treatment on sexual function requires caution to be exercised. Protocol Number NCT00151801, registered in ClinicalTrials.gov.
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. laura.degiglio@uniroma1.it.|Department of Neurology and Psychiatry, Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy. laura.degiglio@uniroma1.it.
authors.forename: Laura
authors.initials: L
authors.lastname: De Giglio
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marinelli
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Valeria T
authors.initials: VT
authors.lastname: Barletta
authors.affiliation: TFS Trial Form Support S.L., Rome, Italy.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Pagano
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: De Angelis
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Petsas
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy.|IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pantano
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tomassini
authors.affiliation: MS Centre Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.|Department of Neurology and Psychiatry, Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
mesh_terms: D000328:Adult; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D017135:Desogestrel / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy*; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C442659:ethinyl estradiol-desogestrel combination; D004997:Ethinyl Estradiol; D017135:Desogestrel; D000068556:Interferon beta-1a