Session Information
Date: Tuesday, October 23, 2018
Title: Systemic Lupus Erythematosus – Clinical Poster III: Treatment
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Ustekinumab (UST), a monoclonal antibody that targets the shared p40 subunit of the cytokines IL-12 & IL-23, is being investigated in patients (pts) w/ active systemic lupus erythematosus (SLE). While traditional 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) can be used to evaluate SLE responses using partial improvement (≥50%) in each domain. To evaluate SLEDAI-2K vs S2K RI-50 response in a randomized, placebo (PBO) controlled trial of UST in pts w/ active SLE.
Methods: We conducted a phase 2, PBO-controlled study in adults w/ active disease (SLEDAI score ≥6 with ≥1 BILAG A &/or ≥2 BILAG B scores) despite standard-of-care therapy. Pts (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 90mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response at wk24 using various thresholds to define response including a decrease of at least 1, 2, 3, 4, 5, or 6 points from baseline in the S2K RI-50 score. We also compared the proportion of patients w/ SLEDAI-2K response vs S2K RI-50 response in pts receiving UST (n=62) vs PBO (n=40) at wk24.
Results: Change from baseline SLEDAI-2K & S2K RI-50 scores were strongly correlated (R=0.92, p<0.0001) at wk24. A greater proportion of UST vs PBO pts achieved S2K RI‑50 response at wk24, regardless of threshold used to define response (Table). The greatest differences in S2K RI‑50 response rates between UST vs PBO were observed for a 4-point decrease (23.3%, p=0.010), a 5-point decrease (22.8%, p=0.023), & a 6-point decrease (26.5%, p=0.014) from baseline. S2K RI-50 captured more responders than SLEDAI-2K at wk24, however, the difference in SLEDAI-2K 4-point response in UST vs PBO was D27% (p=0.005) while S2K RI-50 was D23% (p=0.010).
Conclusion: S2K RI-50 is an instrument that can capture partial clinically important improvement of ≥ 50% in SLE disease manifestations. The data suggests cutpoints for defining S2K RI-50 response in clinical trials of patients with moderate-to-severe SLE disease activity.
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Table 1. S2K RI-50 response rates at Wk24 for various thresholds to define response |
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|
Decrease from Baseline |
UST (%)a,b |
PBO (%)a,b |
Difference between UST & PBO |
p-valuec |
|
1 Point Decrease |
95.3 |
88.6 |
6.7 |
0.1334 |
|
2 Point Decrease |
93.5 |
79.3 |
14.2 |
0.0337 |
|
3 Point Decrease |
84.1 |
70.9 |
13.2 |
0.0820 |
|
4 Point Decrease |
84.0 |
60.7 |
23.3 |
0.0104 |
|
5 Point Decrease |
73.5 |
50.7 |
22.8 |
0.0234 |
|
6 Point Decrease |
70.5 |
44.0 |
26.5 |
0.0138 |
|
Note: S2K RI-50 response is defined differently in each row using different cutoffs. S2K RI-50 uses partial response definition of ≥50% improvement for each individual SLEDAI-2K descriptor. a Values for subjects meeting treatment failure criteria are set to missing from point of treatment failure forward. b Response based upon multiple imputations for missing data from Wk16 to Wk24, where Markov chain Monte Carlo method is used to make missing pattern monotone & serial logistic regression is used to impute monotone missing. The imputation model includes treatment group & baseline SLEDAI-2K covariate. c Test for greater treatment effect in UST over PBO (alternative hypothesis) is based upon logistic regression w/ treatment group, baseline SLEDAI-2K, baseline medication use for SLE & race as covariates. |
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To cite this abstract in AMA style:
Touma Z, Urowitz M, Gladman DD, Wagner C, Zhou B, Gordon R, Hsu B, Chevrier M, Rose S. Sledai-2K Responder Index-50 Is Effective in Demonstrating Partial Response in a Phase 2, Randomized Placebo-Controlled Study of Ustekinumab in Patients with Active Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/sledai-2k-responder-index-50-is-effective-in-demonstrating-partial-response-in-a-phase-2-randomized-placebo-controlled-study-of-ustekinumab-in-patients-with-active-systemic-lupus-erythematosus/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sledai-2k-responder-index-50-is-effective-in-demonstrating-partial-response-in-a-phase-2-randomized-placebo-controlled-study-of-ustekinumab-in-patients-with-active-systemic-lupus-erythematosus/