title: Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease.
abstract: OBJECTIVE
  Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD). Effects of IL6 inhibition on the inflammatory milieu accompanying MCD have not been characterized.
  
  
  METHODS
  Trends in inflammatory- and anemia-associated markers, measured over the course of a placebo-controlled study of siltuximab (11 mg/kg q3w) in patients with MCD (n = 79), were characterized.
  
  
  RESULTS
  Baseline IL6 and C-reactive protein (CRP) levels were significantly correlated (r = 0.708; P < 0.0001). CRP levels decreased (median, 92%) by cycle 1 day 8 (C1D8), remaining suppressed during siltuximab treatment while remaining stable in the placebo group. There were no associations between baseline CRP or IL6 and MCD symptom burden, histologic subtype, ethnicity, maximum CRP decrease, and response parameters. A hemoglobin response (change ≥ 15 g/L at week 13) was observed with siltuximab (61%; P = 0.0002). Median hepcidin decrease from baseline at C1D8 with siltuximab was 47% versus median 11% increase with placebo. Maximum post-baseline changes in hepcidin levels among siltuximab recipients were correlated with maximum changes for hemoglobin (r = -0.395; P = 0.00607), total iron-binding capacity (TIBC; r = -0.354; P = 0.01694), and ferritin (r = 0.599; P = 0.0001). Greater median changes from baseline in ferritin, hemoglobin, and TIBC were observed in anemic siltuximab-treated patients.
  
  
  CONCLUSIONS
  IL6 neutralization with siltuximab resulted in sustained CRP suppression and improvement of anemia, in part, by hepcidin pathway inhibition.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. ccasper@fhcrc.org.
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Shalini
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.affiliation: Sir YK Pao Centre for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaffer
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bandekar
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Brett
authors.initials: B
authors.lastname: Hall
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.affiliation: Janssen Research & Development, Leiden, the Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vermeulen
authors.affiliation: Janssen Research & Development, Spring House, Pennsylvania.
authors.forename: Manjula
authors.initials: M
authors.lastname: Reddy
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein; D005871:Castleman Disease / Q000097:blood* / Q000188:drug therapy*; D004909:Erythrocyte Indices; D005260:Female; D064451:Hepcidins / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D064451:Hepcidins; D015850:Interleukin-6; D007501:Iron; D000093242:Interleukin-6 Inhibitors; C504234:siltuximab