Article Text

PDF
SAT0058 Using the Multi-Biomarker Disease Activity Score as a Complementary Inclusion Criterion for Clinical Trials in Rheumatoid Arthritis May Enhance Recruitment
  1. R.F. van Vollenhoven1,
  2. R. Bolce2,
  3. K. Hambardzumyan1,
  4. S. Saevarsdottir1,
  5. K. Forslind3,
  6. S. Ernestam4,
  7. I.F. Petersson3,
  8. E.H. Sasso2,
  9. C.C. Hwang2,
  10. O.G. Segurado2,
  11. P. Geborek3
  1. 1Karolinska Institutet, Stockholm, Sweden
  2. 2Crescendo Bioscience, South San Francisco, United States
  3. 3Lund University, Lund
  4. 4Karolinska University Hospital, Stockholm, Sweden

Abstract

Background Clinical trials in rheumatoid arthritis (RA) often require elevated C-reactive protein (CRP), e.g., >10 mg/L, to enhance detection of clinical and radiographic efficacy. However, this inclusion criterion may limit recruitment by excluding some patients with active disease. The multi-biomarker disease activity (MBDA) score quantifies disease activity with a score of 1 to 100 and can be high (>44) even when the CRP is ≤10 mg/L.

Objectives To explore the hypothesis that, by using MBDA score >44 as a clinical trial inclusion criterion complementary to CRP>10mg/L, the number of eligible patients can be increased while maintaining the ability to detect treatment responses.

Methods In the SWEFOT trial, DMARD-naïve patients with early RA were enrolled, without a CRP requirement, and received methotrexate (MTX) monotherapy from baseline; at 3 months, non-responders to MTX (NR, DAS28>3.2) received treatment intensification. We analyzed: 1) Patients from baseline to 3 months, and 2) MTX non-responders; for the latter population we used data from month 3 as the de facto baseline and changes from month 3 to 12 as the measured response. In both analyses patients were grouped according to CRP (≤10 vs. >10 mg/L) or MBDA score (≤44 vs. >44) and assessed for clinical outcomes from baseline to 3 months following treatment with MTX, and from 3 to 12 months for add-on therapy (triple therapy or anti-TNF). Radiographic progression was assessed by change in SHS from baseline to 1 year for both analyses.

Results For the DMARD-naïve population (N=220), baseline values and changes from baseline for disease activity measures and ΔSHS were similar for patients with CRP >10 mg/L versus MBDA score >44. Moreover, by adding the 37 patients with MBDA score >44 and CRP ≤10 mg/L to the group with CRP >10 mg/L (N=154), the combined group (N=191) had 24% more patients and similar clinical and radiographic outcomes. Similarly, for the MTX non-responder population (N=127), values at month 3 and changes to month 12 were similar for the CRP >10 mg/L and MBDA >44 groups, and adding the 23 patients with month 3 MBDA score >44 and CRP ≤10 mg/L to the group with CRP >10 mg/L (N=49) created a combined group (N=72) with 47% more patients and similar outcomes. The results are summarized in the table.

Conclusions These data suggest that if a clinical trial of DMARD-naïve or MTX-non-responder patients were to include all patients with MBDA score >44 and/or CRP >10 mg/L, the number of eligible patients can be increased by 24% and 47%, respectively, compared with enrollment based on CRP >10 mg/L alone, while maintaining clinical and radiographic outcomes.

Disclosure of Interest R. van Vollenhoven Grant/research support: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, R. Bolce Shareholder of: Crescendo Bioscience, Employee of: Crescendo Bioscience, K. Hambardzumyan: None declared, S. Saevarsdottir: None declared, K. Forslind: None declared, S. Ernestam: None declared, I. Petersson Speakers bureau: UCB Phama, Pfizer, AbbVie, E. Sasso Shareholder of: Crescendo Bioscience, Employee of: Crescendo Bioscience, C. Hwang Shareholder of: Crescendo Bioscience, Employee of: Crescendo Bioscience, O. Segurado Shareholder of: Crescendo Bioscience, Employee of: Crescendo Bioscience, P. Geborek: None declared

DOI 10.1136/annrheumdis-2014-eular.3329

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.