title: Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis.
abstract: OBJECTIVE
  To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab.
  
  
  METHODS
  We analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti-Mi-2, anti-signal recognition particle, anti-transcription intermediary factor 1γ [TIF-1γ], anti-MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time-to-event analyses. A multivariable time-dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement.
  
  
  RESULTS
  In the final multivariable model, the presence of an antisynthetase, primarily anti-Jo-1 (hazard ratio [HR] 3.08, P < 0.01), anti-Mi-2 (HR 2.5, P < 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations.
  
  
  CONCLUSIONS
  Our findings indicate that the presence of antisynthetase and anti-Mi-2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Rohit
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Andriy
authors.initials: A
authors.lastname: Bandos
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Rider
authors.forename: Michael O
authors.initials: MO
authors.lastname: Harris-Love
authors.forename: Marc C
authors.initials: MC
authors.lastname: Levesque
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001323:Autoantibodies; D003882:Dermatomyositis / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D017285:Polymyositis / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab