title: A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure.
abstract: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs).
  
  
  
  We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each second-line treatment was analyzed at randomization with the Breslow-Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30-44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]).
  
  
  
  Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab.
  
  
  
  In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.
authors.affiliation: Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Karen
authors.initials: K
authors.lastname: Hambardzumyan
authors.affiliation: Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Saedis
authors.initials: S
authors.lastname: Saevarsdottir
authors.affiliation: Lund University and Helsingborg's Lasarett, Helsingborg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Forslind
authors.affiliation: Lund University, Lund, Sweden.
authors.forename: Ingemar F
authors.initials: IF
authors.lastname: Petersson
authors.affiliation: Lund University, Lund, Sweden.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Wallman
authors.affiliation: Institution LIME Medical Management Centre, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ernestam
authors.affiliation: Crescendo Bioscience, Inc., South San Francisco, California.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Bolce
authors.affiliation: Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood; D003661:Decision Support Techniques; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D000069285:Infliximab / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008727:Methotrexate / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D052243:Resistin; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; C499624:RETN protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D052243:Resistin; D000685:Serum Amyloid A Protein; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D004815:Epidermal Growth Factor; D002097:C-Reactive Protein; D000069285:Infliximab; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D008727:Methotrexate