title: A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study.
abstract: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment.
  
  
  
  Patients with RA who were receiving RTX for the first time were included in an observatory registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA (defined as disease activity score in 28 joints (DAS28) ≤3.2) at week 24.
  
  
  
  EULAR responders had lower total lymphocyte counts (LC), T cells and CD4 + T cells at baseline. Although these parameters were independent predictors of EULAR response they failed in determining who would reach LDA. In contrast, LC >2910/μl or plasmablast frequency >2.85 % at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3 % and specificity of 44.8 %.
  
  
  
  A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability.
authors: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
authors: Martin H
authors: MH
authors: Stradner
authors: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
authors: Christian
authors: C
authors: Dejaco
authors: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
authors: Kerstin
authors: K
authors: Brickmann
authors: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
authors: Winfried B
authors: WB
authors: Graninger
authors: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria. hans-peter.brezinsek@medunigraz.at.
authors: Hans Peter
authors: 0000-0002-8939-0505
authors: HP
authors: Brezinschek
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D000069283:Rituximab
keywords: Biomarker; Lymphocytes; Plasmablasts; Rheumatoid arthritis; Rituximab; T cells