title: Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.
abstract: OBJECTIVE
  Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.
  
  
  METHODS
  We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umeå, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%).
  
  
  RESULTS
  Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center).
  
  
  CONCLUSIONS
  Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns. Ann Neurol 2016;79:950-958.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-4710-6326
authors.initials: P
authors.lastname: Alping
authors.affiliation: Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frisell
authors.affiliation: Department of Neurology, Institute of Clinical Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lenka
authors.initials: L
authors.lastname: Novakova
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Protik
authors.initials: P
authors.lastname: Islam-Jakobsson
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Salzer
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Björck
authors.affiliation: Department of Neurology, Institute of Clinical Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Axelsson
authors.affiliation: Department of Neurology, Institute of Clinical Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Malmeström
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Neurology, Institute of Clinical Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.|Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007577:JC Virus / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use*; D012008:Recurrence; D012042:Registries; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D000069442:Natalizumab; D000069283:Rituximab; D000068876:Fingolimod Hydrochloride