10 Performance of SLEDAI-2K Responder Index-50 in a Randomized Placebo-Controlled Trial with Ustekinumab (UST) in Systemic Lupus Erythematosus

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 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.