Article Text

Evaluation of different methods used to assess disease activity in rheumatoid arthritis: analyses of abatacept clinical trial data
  1. M Dougados1,
  2. N Schmidely2,
  3. M Le Bars2,
  4. C Lafosse3,
  5. M Schiff4,
  6. J S Smolen5,
  7. D Aletaha5,
  8. P van Riel6,
  9. G Wells7
  1. 1
    Rene Descartes University, Medicine Faculty, UPRES–EA 4058, APHP, Cochin Hospital, Rheumatology B Department, Paris, France
  2. 2
    Bristol-Myers Squibb, Rueil-Malmaison, France
  3. 3
    Aixial, Levallois-Perret, France
  4. 4
    University of Colorado, Denver, Colorado, USA
  5. 5
    Department of Rheumatology, Medical University of Vienna, Vienna, Austria
  6. 6
    University Hospital Nijmegen, Nijmegen, The Netherlands
  7. 7
    University of Ottawa, Ottawa, Ontario, Canada
  1. Dr M Dougados, Hopital Cochin, Rene Descartes University, Service de Rhumatologie B, 27 Rue du Faubourg Saint Jacques, Paris 75014, France; maxime.dougados{at}cch.ap-hop-paris.fr

Abstract

Objectives: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial.

Methods: 424 active (abatacept ∼10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. Methods of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28 ⩽3.2) vs DAS28-defined remission (DAS28 <2.6)); (3) time to onset (time to first ACR50/LDAS) and (4) sustainability of ACR50/LDAS for consecutive visits. Methods were assessed according to: (1) discriminatory capacity (number of patients needed to study (NNS)); (2) structural progression (Genant-modified Sharp score) and (3) patient satisfaction with treatment. Positive likelihood ratios (LR) evaluated the ability of the above methods to reflect structural damage and patient satisfaction.

Results: MDAS and ACR20 had the highest discriminatory capacity (NNS 49 and 69). Sustained LDAS best reflected no radiographic progression (positive LR ⩾2). More stringent criteria (at least ACR50/LDAS), faster onset (⩽3 months) and sustainability (>3 visits) of ACR50/LDAS best reflected patient satisfaction (positive LR >10).

Conclusions: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.

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Footnotes

  • Competing interests: Declared. CL is an employee of Axial; NS and MLB are employees of Bristol-Myers Squibb and own stocks and options; DA has received consultancies and honoraria from Bristol-Myers Squibb; GW has received consultancies, speaking fees and honoraria from Bristol-Myers Squibb; MD has received consultancies, speaking fees and honoraria from Bristol-Myers Squibb, Abbott, Wyeth, UCB and Roche; PvR has nothing to disclose; MS has received consultancies from Abbott, Amgen, Bristol-Myers Squibb, Wyeth-Ayrest and UCB, speaking fees from Abbott, Amgen and Wyeth-Ayrest and grants from Abbott, Amgen, Bristol-Myers Squibb, UCB, Centocor, Roche, Genentech and Targeted Genetics; JSS has received honoraria and a research grant from Bristol-Myers Squibb.

  • Funding: This study was supported in part by an unrestricted research grant-in-aid from Bristol-Myers Squibb. Editorial assistance was provided by Medicus International and funded by Bristol-Myers Squibb. Under direction of the authors, editorial assistance was provided at the first draft stage and during subsequent revision of the manuscript.

  • Ethics approval: Ethics approval was obtained.

  • ▸ Additional supplemental tables are published online only at http://ard.bmj.com/content/vol68/issue4