title: A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design.
abstract: BACKGROUND
  Tovaxin is an autologous T-cell immunotherapy under investigation for the treatment of MS. The product consists of in vitro expanded myelin-reactive T-cells manufactured against up to six immunodominant peptides derived from three myelin antigens.
  
  
  METHODS
  A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing-remitting MS and clinically isolated syndrome subjects.
  
  
  RESULTS
  Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease-modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naïve subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR ≥ 1, ARR>1). However, clinical benefit was not was accompanied by a treatment-dependent improvement in MRI measures.
  
  
  CONCLUSIONS
  Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment-naïve individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration.
authors: Central Texas Neurology Consultants, Round Rock, TX 78681, USA.
authors: Edward
authors: E
authors: Fox
authors: Daniel
authors: D
authors: Wynn
authors: Stanley
authors: S
authors: Cohan
authors: Donna
authors: D
authors: Rill
authors: Dawn
authors: D
authors: McGuire
authors: Clyde
authors: C
authors: Markowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D009186:Myelin Sheath / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States; D014612:Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D016056:Immunodominant Epitopes; D014612:Vaccines; C540587:tovaxin