title: Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.
abstract: To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels.
  
  
  
  We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]).
  
  
  
  Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ≥1 swollen joint (1.74 μg/ml versus 3.04 μg/ml; P = 0.010). Using DAS28 ≥2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ≥2.47 μg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (ρ = -0.671, P < 0.001) and IFX (ρ = -0.729, P = 0.017).
  
  
  
  Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acute-phase reactants, even in patients with low inflammatory activity.
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: José
authors: J
authors: Inciarte-Mundo
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Maria
authors: 0000-0001-6657-2333
authors: M
authors: Victoria Hernández
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Virginia
authors: V
authors: Ruiz-Esquide
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Sonia
authors: S
authors: Raquel Cabrera-Villalba
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Julio
authors: J
authors: Ramirez
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Andrea
authors: A
authors: Cuervo
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Mariona
authors: M
authors: Pascal
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Jordi
authors: J
authors: Yagüe
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Juan D
authors: JD
authors: Cañete
authors: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors: Raimon
authors: R
authors: Sanmarti
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis*; D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D000069285:Infliximab / Q000627:therapeutic use; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000209:Acute-Phase Proteins; D018501:Antirheumatic Agents; D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept