title: Treatment of relapsing-remitting multiple sclerosis after 24 doses of natalizumab: evidence from an Italian spontaneous, prospective, and observational study (the TY-STOP Study).
abstract: OBJECTIVE
  The evaluation of therapeutic choices is needed after 24 doses of natalizumab in patients with multiple sclerosis (MS).
  
  
  OBJECTIVE
  To evaluate the effect of therapeutic choices on the mean annualized relapse rate and on magnetic resonance imaging MS activity after 24 doses of natalizumab in patients with relapsing-remitting MS.
  
  
  METHODS
  The TY-STOP study, which recruited participants between October 22, 2010, and October 22, 2012, at 8 Italian MS centers (secondary care outpatient clinics) among 124 adult patients who demonstrated no clinical or magnetic resonance imaging MS activity after 24 doses of natalizumab.
  
  
  METHODS
  Natalizumab, no treatment, interferon beta, glatiramer acetate, or fingolimod.
  
  
  METHODS
  The primary end point was the mean annualized relapse rate. Statistical analyses were performed in 124 patients with complete follow-up data among 130 patients who were recruited and stratified into study groups. In the intent-to-treat group, the decision was made to continue or interrupt natalizumab after 24 doses. In the as-treated group, natalizumab continuers received natalizumab, natalizumab switchers changed to different therapies, and natalizumab quitters discontinued natalizumab during the study year.
  
  
  RESULTS
  No significant differences in demographic or baseline clinical characteristics were found among the study participants. In the intent-to-treat group (n = 124), clinical (P = .004) and radiologic (P = .02) MS activity was significantly lower in patients continuing natalizumab (n = 43) than in patients interrupting natalizumab (n = 81), with a protective effect of natalizumab continuation on both outcomes (odds ratio [OR], 0.33; 95% CI, 0.15-0.70 for clinical activity and OR, 0.35; 95% CI, 0.15-0.79 for radiologic activity). In the as-treated group (n = 124), clinical (P = .003) and radiologic (P = .03) MS activity was significantly lower in natalizumab continuers than in natalizumab switchers or quitters, confirming a protective effect of natalizumab on the risk of relapse in natalizumab continuers compared with natalizumab quitters (OR, 4.40; 95% CI, 1.72-11.23) and natalizumab switchers (OR, 3.28; 95% CI, 0.99-10.79). No disease rebound was observed in natalizumab quitters. After natalizumab discontinuation, 1 patient developed progressive multifocal leukoencephalopathy during the observation period, with complete recovery.
  
  
  CONCLUSIONS
  This study provides class III evidence of an increased risk of MS activity resumption after natalizumab discontinuation. Therapy discontinuation after 24 doses in natalizumab-responding patients should be considered only if the risk of progressive multifocal leukoencephalopathy is high and outweighs the benefits of continuing the drug.
  
  
  BACKGROUND
  Osservatorio Nazionale Sulla Sperimentazione Clinica dei Medicinali No. 131/2010.
authors: Division of Neurology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy.
authors: Marinella
authors: M
authors: Clerico
authors: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors: Irene
authors: I
authors: Schiavetti
authors: Division of Neurology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy.
authors: Stefania F
authors: SF
authors: De Mercanti
authors: Division of Neurology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy.
authors: Federico
authors: F
authors: Piazza
authors: Department of Oncology, University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy.
authors: Dario
authors: D
authors: Gned
authors: Department of Neurosciences, Reproductive, and Odontostomatological Sciences, Federico II University of Naples, Naples, Italy.
authors: Vincenzo
authors: V
authors: Brescia Morra
authors: Department of Neurosciences, Reproductive, and Odontostomatological Sciences, Federico II University of Naples, Naples, Italy.
authors: Roberta
authors: R
authors: Lanzillo
authors: Department of Neurology II, Center of Multiple Sclerosis, Azienda Ospedaliera Sant'Antonio Abate Hospital, Gallarate, Italy.
authors: Angelo
authors: A
authors: Ghezzi
authors: Department of Neurology II, Center of Multiple Sclerosis, Azienda Ospedaliera Sant'Antonio Abate Hospital, Gallarate, Italy.
authors: Anna
authors: A
authors: Bianchi
authors: Section of Neurology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
authors: Giuseppe
authors: G
authors: Salemi
authors: Section of Neurology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
authors: Sabrina
authors: S
authors: Realmuto
authors: Neurology Unit, Department of Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Patrizia
authors: P
authors: Sola
authors: Neurology Unit, Department of Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Francesca
authors: F
authors: Vitetta
authors: Division of Neurology and Multiple Sclerosis Center, Department of Neurosciences, University of Turin, Città della Salute e della Scienza University Hospital, Turin, Italy.
authors: Paola
authors: P
authors: Cavalla
authors: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors: Damiano
authors: D
authors: Paolicelli
authors: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors: Maria
authors: M
authors: Trojano
authors: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors: Maria Pia
authors: MP
authors: Sormani
authors: Division of Neurology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy.
authors: Luca
authors: L
authors: Durelli
mesh_terms: D000328:Adult; D006801:Humans; D008297:Male; D008875:Middle Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D007558:Italy; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D000069442:Natalizumab; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab