title: When to adjust therapy in patients with rheumatoid arthritis after initiation of etanercept plus methotrexate or methotrexate alone: findings from a randomized study (COMET).
abstract: OBJECTIVE
  The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) ≥ 3.2] of 3-24 months' duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy).
  
  
  RESULTS
  The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group.
  
  
  CONCLUSIONS
  High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year.
authors.affiliation: From Paris-Descartes University and the Rheumatology B Department, Cochin Hospital, Paris, France; the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Pfizer France, Paris, France; and Pfizer Inc., Collegeville, Pennsylvania, USA.M.R. Dougados, MD, Professor of Rheumatology, Paris-Descartes University and Rheumatology B Department, Cochin Hospital; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; Y. Brault, MS, Director of Biostatistics, Pfizer France; A.S. Koenig, DO, Inflammation and Immunology Group Lead, North America Medical Affairs, Pfizer Inc.; I.S. Logeart, MD, Medical Director, Inflammation Europe, Pfizer France. maxime.dougados@cch.aphp.fr.
authors.forename: Maxime R
authors.initials: MR
authors.lastname: Dougados
authors.affiliation: From Paris-Descartes University and the Rheumatology B Department, Cochin Hospital, Paris, France; the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Pfizer France, Paris, France; and Pfizer Inc., Collegeville, Pennsylvania, USA.M.R. Dougados, MD, Professor of Rheumatology, Paris-Descartes University and Rheumatology B Department, Cochin Hospital; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; Y. Brault, MS, Director of Biostatistics, Pfizer France; A.S. Koenig, DO, Inflammation and Immunology Group Lead, North America Medical Affairs, Pfizer Inc.; I.S. Logeart, MD, Medical Director, Inflammation Europe, Pfizer France.
authors.forename: Désirée M
authors.initials: DM
authors.lastname: van der Heijde
authors.affiliation: From Paris-Descartes University and the Rheumatology B Department, Cochin Hospital, Paris, France; the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Pfizer France, Paris, France; and Pfizer Inc., Collegeville, Pennsylvania, USA.M.R. Dougados, MD, Professor of Rheumatology, Paris-Descartes University and Rheumatology B Department, Cochin Hospital; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; Y. Brault, MS, Director of Biostatistics, Pfizer France; A.S. Koenig, DO, Inflammation and Immunology Group Lead, North America Medical Affairs, Pfizer Inc.; I.S. Logeart, MD, Medical Director, Inflammation Europe, Pfizer France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Brault
authors.affiliation: From Paris-Descartes University and the Rheumatology B Department, Cochin Hospital, Paris, France; the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Pfizer France, Paris, France; and Pfizer Inc., Collegeville, Pennsylvania, USA.M.R. Dougados, MD, Professor of Rheumatology, Paris-Descartes University and Rheumatology B Department, Cochin Hospital; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; Y. Brault, MS, Director of Biostatistics, Pfizer France; A.S. Koenig, DO, Inflammation and Immunology Group Lead, North America Medical Affairs, Pfizer Inc.; I.S. Logeart, MD, Medical Director, Inflammation Europe, Pfizer France.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Koenig
authors.affiliation: From Paris-Descartes University and the Rheumatology B Department, Cochin Hospital, Paris, France; the Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Pfizer France, Paris, France; and Pfizer Inc., Collegeville, Pennsylvania, USA.M.R. Dougados, MD, Professor of Rheumatology, Paris-Descartes University and Rheumatology B Department, Cochin Hospital; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; Y. Brault, MS, Director of Biostatistics, Pfizer France; A.S. Koenig, DO, Inflammation and Immunology Group Lead, North America Medical Affairs, Pfizer Inc.; I.S. Logeart, MD, Medical Director, Inflammation Europe, Pfizer France.
authors.forename: Isabelle S
authors.initials: IS
authors.lastname: Logeart
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012074:Remission Induction; D019233:Retreatment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000068800:Etanercept; D008727:Methotrexate
keywords: BIOLOGIC AGENTS; EARLY RHEUMATOID ARTHRITIS; ETANERCEPT; METHOTREXATE; REMISSION; TREATMENT