title: Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review.
abstract: BACKGROUND
  Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of rituximab for MS treatment.
  
  
  METHODS
  Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.
  
  
  RESULTS
  Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. AUTHOR’S CONCLUSION: Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA. tamara.castillo@biodonostia.org
authors.forename: Tamara
authors.initials: T
authors.lastname: Castillo-Trivino
authors.forename: Dejana
authors.initials: D
authors.lastname: Braithwaite
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002986:Clinical Trials as Topic; D016206:Databases, Bibliographic; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab