title: Predictors of freedom from disease activity in natalizumab treated-patients with multiple sclerosis.
abstract: OBJECTIVE
  To identify baseline predictors of the response to natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  We prospectively collected clinical and magnetic resonance imaging (MRI) data of RRMS patients treated with natalizumab and followed-up for 24 months. They were categorized according to different outcomes of response to natalizumab: (i) "full" responders, i.e. those having no relapses, no sustained disability worsening on Expanded Disability Status Scale (EDSS), and no MRI activity; (ii) "partial" responders, i.e. those having MRI activity, but not relapses and/or EDSS worsening; and (iii) "poor" responder, i.e. those experiencing relapses and/or EDSS worsening.
  
  
  RESULTS
  We analysed data of 210 RR-MS patients (147 F, 63 M); at the end of the 24-month study period, 120 (57.1%), 36 (17.1%), and 54 (25.8%) patients were defined as "full", "partial" or "poor" responders, respectively. Thirty-two (89%) patients classified as "partial" responders experienced MRI activity at the 6-month scan; the majority of them had >2 contrast-enhancing lesions at baseline MRI scan or >2 relapses in the year prior to starting therapy. A "full" response to natalizumab was found more likely in patients with ≤ 2 relapses in the year prior to treatment start (OR=3.68; p=0.002), and in those with an EDSS score ≤ 2.5 at baseline (OR=3.60; p<0.001). Accordingly, patients with >2 relapses in the year prior to treatment start, or those with an EDSS score ≥ 3.0 at baseline were more likely to be classified as "poor responders". These figures were replicated even after excluding 20 patients who developed anti-natalizumab antibodies.
  
  
  CONCLUSIONS
  Our results suggest that natalizumab may lead to a complete remission of MS if started in patients with less aggressive disease (i.e. few relapses and mild disability), thus suggesting its possible role as first switching option, or even first-line therapy, at least in JCV-negative patients. We also support the recommendation against an immediate discontinuation of despite the occurrence of MRI activity in the first few months of treatment, since the freedom from clinical disease activity could be still achieved.
authors.affiliation: Dept. of Neurology and Psychiatry, Multiple Sclerosis Centre, S. Andrea Hospital, Sapienza University, Rome, Italy. luca.prosperini@uniroma1.it
authors.forename: Luca
authors.initials: L
authors.lastname: Prosperini
authors.forename: Costanza
authors.initials: C
authors.lastname: Giannì
authors.forename: Valeria
authors.initials: V
authors.lastname: Barletta
authors.forename: Chiara
authors.initials: C
authors.lastname: Mancinelli
authors.forename: Federica
authors.initials: F
authors.lastname: Fubelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borriello
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002464:Cell Migration Inhibition / Q000187:drug effects; D018572:Disease-Free Survival; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D011358:Product Surveillance, Postmarketing; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy; D012720:Severity of Illness Index; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab