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28 Drivers of the sle responder index (sri-5) endpoint in clinical trials of sle
  1. K Kalunian1,
  2. M Urowitz2,
  3. D Isenberg3,
  4. J Merrill4,
  5. M Petri5,
  6. R Furie6,
  7. MA Morgan-Cox7,
  8. R Taha7,
  9. M Silk8 and
  10. M Linnik9
  1. 1University of California- San Diego School of Medicine, Medicine, San Diego, USA
  2. 2University of Toronto Faculty of Medicine, Medicine, Tornoto, Canada
  3. 3University College London, Rheumatology, London, UK
  4. 4University of Oklahoma College of Medicine, Rheumatology, Oklahoma City, USA
  5. 5Johns Hopkins University School of Medicine, Rheumatology, Baltimore, USA
  6. 6Hofstra North Shore-LIJ School of Medicine, Rheumatology, Great Neck, USA
  7. 7Eli Lilly, Statistics, Indianapolis, USA
  8. 8Eli Lilly, Immunology, Indianapolis, USA
  9. 9Lilly Biotechnology Centre, Immunology, San Diego, USA

Abstract

Background and Aims SRI is a composite endpoint used in many SLE trials. The current investigation sought to identify those SRI components that drive response.

Methods This study evaluated data from two large multinational trials that used SRI-5 as primary endpoint (n=2262 patients).

Results The overall SRI-5 response rate was 32.8%. Non-response due to lack of a 5-point SLEDAI improvement, conmed violation or dropout were observed in 31%, 16.5% and 19.1%, respectively. In contrast, only 0.5% (11/2262) of patients failed to respond due to deterioration by BILAG or PGA, once achieving the first three components.

The most common SLEDAI organ systems involved at baseline were mucocutaneous (90.6%), musculoskeletal (82.9%) and immunologic (71.6%). The 6 other SLEDAI-defined organ systems were active in ≤11% of patients.

At least one SLEDAI manifestation with low prevalence and high score (≥4 pts) was present in 18.1% and 17.2% of patients in Trials 1 and 2, respectively. SRI-5 response rates for these patients were higher, regardless of treatment assignment.

Conclusions The SRI-5 response is driven by SLEDAI improvement, concomitant medication adherence and trial completion. Patients with less frequent, more severe manifestations had high placebo response rates. A simple dichotomous improvement in SLEDAI score, coupled with successful trial completion and medication stability, provides a more efficient, clinically relevant approach to assess outcome.

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