title: Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis.
abstract: Recent works have suggested a possible link between interleukin (IL)-33 and B-cell biology. We aimed to study the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients in different cohorts with an accurate enzyme-linked immunosorbent assay (ELISA).
  
  
  
  Serum IL-33, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and high serum immunoglobulin (Ig)G levels were assessed in 111 RA patients receiving a first course of 2 g RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Univariate and multivariate analyses identified factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.
  
  
  
  At week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33.5% of the patients. In the combined cohorts, the presence of RF or anti-CCP (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.13-9.46; p = 0.03), high serum IgG (OR 2.32, 95% CI 1.01-5.33; p = 0.048), and detectable serum IL-33 (OR 2.40, 95% CI 1.01-5.72; p = 0.047) were all associated with RTX response in multivariate analysis. The combination of these three factors increased the likelihood of response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the three risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the three risk factors 29.61, 95% CI 1.30-674.79; p = 0.034).
  
  
  
  Detectable serum IL-33 may predict clinical response to RTX independently of, and synergistically with, auto-antibodies and serum IgG level.
  
  
  
  NCT01126541 ; 18 May 2010.
authors.affiliation: Université Paris 06, AP-HP St-Antoine hospital, Rheumatology Department, INSERM UMRS_938, DHU i2B, Paris, France. jeremie.sellam@aphp.fr.|Service de Rhumatologie, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France. jeremie.sellam@aphp.fr.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.affiliation: Université Paris-Sud, AP-HP Hôpitaux Universitaires Paris-Sud, Rheumatology Department, Center for Immunology of Viral Infections and Autoimmune Diseases INSERM U1184, Le Kremlin Bicêtre, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Rivière
authors.affiliation: Université Paris 06, AP-HP St-Antoine hospital, Rheumatology Department, INSERM UMRS_938, DHU i2B, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Courties
authors.affiliation: Biological Immunology Department, ERTICa Research Group, Clermont-Ferrand University Hospital, Clermont-Ferrand, EA4677, France.
authors.forename: Paul-Olivier
authors.initials: PO
authors.lastname: Rouzaire
authors.affiliation: Rheumatology Department, Catholic University of the Sacred Heart, Roma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tolusso
authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Vital
authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Rheumatology Department, Catholic University of the Sacred Heart, Roma, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
authors.affiliation: Rheumatology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Soubrier
authors.affiliation: Université Paris-Sud, AP-HP Hôpitaux Universitaires Paris-Sud, Rheumatology Department, Center for Immunology of Viral Infections and Autoimmune Diseases INSERM U1184, Le Kremlin Bicêtre, France.
authors.forename: Bineta
authors.initials: B
authors.lastname: Ly
authors.affiliation: AP-HP Bicêtre Hospital, Biological Immunology Department, INSERM U1184, Le Kremlin Bicêtre, France.
authors.forename: Houria
authors.initials: H
authors.lastname: Hendel Chavez
authors.affiliation: AP-HP Bicêtre Hospital, Biological Immunology Department, INSERM U1184, Le Kremlin Bicêtre, France.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Taoufik
authors.affiliation: Department of Rheumatology - Hôpital Cochin, Paris Descartes University, Assistance Publique - Hôpitaux de Paris, INSERM (U1153), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Université Paris-Sud, AP-HP Hôpitaux Universitaires Paris-Sud, Rheumatology Department, Center for Immunology of Viral Infections and Autoimmune Diseases INSERM U1184, Le Kremlin Bicêtre, France. xavier.mariette@aphp.fr.|Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, Le Kremlin Bicêtre, 94275, France. xavier.mariette@aphp.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D000067596:Interleukin-33 / Q000097:blood; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C506536:IL33 protein, human; D000067596:Interleukin-33; D000069283:Rituximab
keywords: B-cell; Interleukin 33; Personalized medicine; Rheumatoid arthritis; Rituximab