title: Biologic predictors of clinical improvement in rituximab-treated refractory myositis.
abstract: BACKGROUND
  To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab.
  
  
  METHODS
  In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n = 177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n = 28, TIF-γ n = 19, Mi-2 n = 25, SRP n = 21, MJ n = 18, non-MAA n = 24, unidentified autoantibody n = 9, and no autoantibodies n = 33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons.
  
  
  RESULTS
  The mean (SD) values for muscle disease and physician global disease activity VAS scores (0-100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p < 0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (- 6.7, - 6.1 and -7.2, p < .001). Both IFNCK high scores (>30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p = 0.075).
  
  
  CONCLUSIONS
  Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab.
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, Duke University School of Medicine, 201 Trent Drive, Durham, NC, 27710, USA. ann.reed@duke.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, MN, USA. crowson@mayo.edu.|Division of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. crowson@mayo.edu.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Crowson
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, MN, USA. hein.molly@mayo.edu.
authors.forename: Molly
authors.initials: M
authors.lastname: Hein
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, MN, USA. lopezdepadilla.consuelo@mayo.edu.
authors.forename: Consuelo Lopez
authors.initials: CL
authors.lastname: de Padilla
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, MN, USA. olazagastilourido.jeannette@mayo.edu.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Olazagasti
authors.affiliation: Division of Rheumatology, University of Pittsburgh, Pittsburgh, PA, USA. aggarwalr@upmc.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL, USA. DAscherman@med.miami.edu.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
authors.affiliation: Division of Rheumatology, University of Pittsburgh, Pittsburgh, PA, USA. marclevesque01581@gmail.com.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Levesque
authors.affiliation: Division of Rheumatology, University of Pittsburgh, Pittsburgh, PA, USA. cvo5@pitt.edu.
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D003882:Dermatomyositis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D017285:Polymyositis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D000069283:Rituximab