Article Text

Download PDFPDF

10 Performance of SLEDAI-2K Responder Index-50 in a Randomized Placebo-Controlled Trial with Ustekinumab (UST) in Systemic Lupus Erythematosus
  1. Zahi Touma1,
  2. Dafna D Gladman1,
  3. Kaiyin Fei2,
  4. Y Irene Gregan2,
  5. Robert Gordon2,
  6. Kim Hung Lo2,
  7. Shawn Rose2 and
  8. Murray B Urowitz3
  1. 1Krembil Research Institute, University of Toronto
  2. 2Janssen Research and Development, LLC
  3. 3Krembil Research Institute, University of Toronto


Background While traditional Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) scoring assesses complete SLE response for individual disease manifestations, the SLEDAI-2K Responder Index-50 (S2K RI-50) evaluates responses using partial improvement (50%) in each of the 9 organ-systems of SLEDAI-2K and generates a total score. We aimed to evaluate the performance of S2K RI-50 at 24 weeks in a randomized, placebo (PBO) controlled trial of UST in patients with moderate-to-severe SLE disease activity to ascertain a minimal threshold of partial improvement.

Methods The UST phase 2, PBO-controlled study enrolled adults with active disease (SLEDAI score 6 with 1 BILAG A and /or 2 BILAG B scores) despite standard-of-care therapy. Patients (n=102) were randomized (3:2) to receive UST IV~6 mg/kg or PBO at week (wk) 0, followed by SC injections of UST 90 mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response in patients receiving UST (n=62) vs PBO (n=40) at wk24 using increasing S2K RI-50 reductions of 1, 2, 3, 4, 5, or 6 points from baseline to determine 50% improvement. In order to determine a minimal cut-off to discriminate a treatment effect reflecting partial improvement, nominal level was set at 0.05 for this post hoc analysis.

Results The performance of S2K RI-50 in detecting the treatment difference between UST and PBO with various cut-offs is presented in table 1. A 2-point reduction in S2K RI-50 was the lowest threshold to demonstrate a p-value<0.05. As an example, this could reflect partial improvement in one of the following: renal, arthritis, or myositis, or partial improvement in two of the following disease manifestations: rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement or increased anti-dsDNA.

Abstract 10 Table 1

S2K RI-50 response rates at Wk24 for various cut-offs to define response

Conclusions S2K RI-50 captures partial improvement of 50% in SLE disease activity in the most common disease manifestations in SLE. S2K RI-50 could be used as an outcome in clinical trials as a clinically meaningful measure of partial improvement.

Funding Source(s): Jannsen Research and Development, LLC, supported this study.

Statistics from

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.