ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2055

SRI-4 and BICLA: How Well Do They Agree Across Trials of Active Systemic Lupus Erythematosus?

Alfredo Aguirre1, Mimi Kim2, Kosalaram Goteti3, Ying Li3, Amy Kao4, Nathalie Franchimont5, George Kong5, Catherine Barbey6, Qing Zuraw7, Robert Gordon7, David Manner8, Maria Silk9, Teodora Staeva10, Hoang Nguyen11, Richard Furie12, Matthew Linnik13 and Maria Dall'Era14, 1University of California, San Francisco, San Francisco, CA, 2Albert Einstein College of Medicine, Larchmont, NY, 3EMD Serono, Boston, MA, 4EMD Serono, Billerica, MA, 5Biogen, Cambridge, MA, 6Biogen, Baar, Switzerland, 7Janssen Research and Development, LLC, Spring House, PA, 8Eli Lilly and Company, Indianapolis, IN, 9Eli Lilly, Carmel, IN, 10Lupus Research Alliance, New York, NY, 11Lupus Research Alliance, Houston, TX, 12Northwell Health, Great Neck, NY, 13Eli Lilly and Company, San Diego, CA, 14University of California, Division of Rheumatology, San Francisco, CA

Meeting: ACR Convergence 2022

Keywords: , ,

Session Information

Date: Monday, November 14, 2022

Title: SLE – Diagnosis, Manifestations, and Outcomes Poster III: Outcomes

Session Type: Poster Session D

Session Time: 1:00PM-3:00PM

Background/Purpose: The Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) are currently the most common primary endpoints in systemic lupus erythematosus (SLE) randomized-controlled trials (RCTs). However, discordance between SRI-4 and BICLA effect sizes in studies has engendered skepticism about the utility of these composite indices. In this post-hoc analysis of data from six RCTs of non-renal SLE, we examined concordance and discordance in the SRI-4 and BICLA outcome measures among placebo recipients, and explored reasons for SRI-4/BICLA nonresponse.

Methods: Placebo data from SLE RCTs of 24- or 52-week duration that collected the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and BILAG 2004 Index were included. Participants in each study were classified as either a responder or nonresponder by the SRI-4 and BICLA composite indices, and frequencies of concordance and discordance between the SRI-4 and BICLA were determined. Overall agreement between SRI-4 and BICLA was estimated by Cohen’s kappa. For each participant, the leading reason for nonresponse by the SRI-4 and BICLA was identified by the following hierarchical order: concomitant medication violation; study withdrawal; lack of improvement by SLEDAI or BILAG, respectively; worsening disease by BILAG; worsening disease by SLEDAI (as a criterion for BICLA nonresponse); and worsening physician global assessment.

Results: Five of six RCTs had a requirement for minimum total or clinical SLEDAI score at entry (Table 1). Four trials had primary endpoints of SRI-4 or SRI-5, and all had steroid dose limits at baseline. Placebo response rates ranged from 29-48% with SRI-4 as the outcome and 28-45% with BICLA as the outcome. As shown in Figure 1, SRI-4 and BICLA concordance varied by clinical trial with a Cohen’s kappa ranging from 0.39-0.76. Within trials that provided data at both timepoints, agreement of SRI-4 and BICLA was higher at 52 weeks than at 24 weeks. The three most common reasons for SRI-4 and BICLA nonresponse were lack of SLEDAI or BILAG improvement, respectively, study withdrawal, or concomitant medication violation (Figure 2).

Conclusion: Discordance between the SRI-4 and BICLA varied by clinical trial, ranging from 11.8-30.3%, with SRI-4 classifying more responders than the BICLA. Nonresponse to SRI-4 and BICLA was largely due to lack of clinical improvement by the SLEDAI or BILAG, respectively, study withdrawal, or concomitant medication violation. The remaining components of the SRI-4 and BICLA provided minimal impact to nonresponder frequencies. Further research will identify the specific factors associated with SRI-4 and BICLA discordance.

Supporting image 1

Table 1: Summary of the SLE RTCs and their respective SRI_4 and BICLA responses among the placebo groups

Supporting image 2

Figure 1: Concordance between SRI_4 and BICLA outcomes among placebo recipients of each clinical trial.

Supporting image 3

Figure 2: Reasons for SRI_4 and BICLA nonresponse among placebo recipients, by clinical trial. 2A) Reasons for SRI_4 nonresponse. 2B) Reasons for BICLA nonresponse. SLEDAI: Systemic Lupus Erythematosus Disease Activity Index. BILAG: British Isles Lupus Assessment Group Index. PGA: Physician Global Assessment.

Disclosures: A. Aguirre, None; M. Kim, None; K. Goteti, EMD Serono; Y. Li, EMD Serono; A. Kao, EMD Serono, Billerica, MA, USA; N. Franchimont, Biogen, OMass Therapeutics, Alexion (spouse), AstraZeneca (spouse); G. Kong, None; C. Barbey, Biogen; Q. Zuraw, Janssen Research & Development, LLC; R. Gordon, Janssen Research & Development, LLC; D. Manner, Eli Lilly; M. Silk, Eli Lilly; T. Staeva, None; H. Nguyen, None; R. Furie, AstraZeneca, Biogen; M. Linnik, Eli Lilly; M. Dall'Era, GlaxoSmithKline (GSK), AstraZeneca, Aurinia, BMS, Amgen.

To cite this abstract in AMA style:

Aguirre A, Kim M, Goteti K, Li Y, Kao A, Franchimont N, Kong G, Barbey C, Zuraw Q, Gordon R, Manner D, Silk M, Staeva T, Nguyen H, Furie R, Linnik M, Dall'Era M. SRI-4 and BICLA: How Well Do They Agree Across Trials of Active Systemic Lupus Erythematosus? [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/sri-4-and-bicla-how-well-do-they-agree-across-trials-of-active-systemic-lupus-erythematosus/. Accessed .

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