title: Clinical baseline factors predict response to natalizumab: their usefulness in patient selection.
abstract: BACKGROUND
  Optimal patient selection would improve the risk-benefit ratio of natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS). Clinical features of subjects responding to natalizumab have not been univocally recognized.
  
  
  METHODS
  Longitudinal data on RR MS patients treated with natalizumab in Liguria, Italy are reported. Predictors of relapse occurrence and disability improvement were analyzed with a logistic regression method in subjects treated for one year (N = 62). A new score, called "Better EDSS Trend (BET)", was devised to describe the impact of the treatment on disability. Changes in annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two years and proportion of disease-free patients were evaluated.
  
  
  RESULTS
  Previous EDSS worsening plus ARR ≥ 2 increased the risk of relapse during the treatment [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in disability at one year. EDSS 3.0-3.5 or high disease activity were associated with neurological improvement in the first year of treatment (respectively OR 5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in the disability trend, was observed in 40.3% of patients, and correlated with high ARR in the year before treatment (OR 1.69, P = 0.03).
  
  
  CONCLUSIONS
  Subjects with EDSS 3.0-3.5 and those with very active disease in the year before treatment are most likely to improve in neurological function under natalizumab. A relapse in the first year of treatment is associated to high pre-treatment disease activity; however, since the occurrence of a relapse did not have a negative impact on clinical improvement at one year, we suggest that it should not lead to treatment discontinuation. We propose BET as an additional endpoint of treatment response in MS.
authors.forename: Alice
authors.initials: A
authors.lastname: Laroni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gandoglia
authors.forename: Claudio
authors.initials: C
authors.lastname: Solaro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ribizzi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Tassinari
authors.forename: Matteo
authors.initials: M
authors.lastname: Pizzorno
authors.forename: Sergio
authors.initials: S
authors.lastname: Parodi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Baldassarre
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rilla
authors.forename: Simonetta
authors.initials: S
authors.lastname: Venturi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Capello
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Largo Daneo 3, 16132 Genova, Italy. glmancardi@neurologia.unige.it.
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: Mancardi
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab; D018579:Patient Selection; D011237:Predictive Value of Tests; D012008:Recurrence; D012107:Research Design; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab