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Abstract
Background Development of effective new Systemic Lupus Erythematosus (SLE) treatments requires a validated responder index responsive to clinically meaningful change and relevant to clinical practice. To address this challenge, we have recently developed a new Lupus Multivariable Outcome Score (LuMOS) to optimize discrimination between outcomes of actively treated patients versus those on placebo.1 We now report on external validation of LuMOS in two independent SLE clinical trials.
Methods Validation was carried out in the Illuminate trials that evaluated tabalumab (TB) in SLE. All participants in both Illuminate 1 and 2 trials met the ACR classification criteria for SLE and all were included in our analyses. To adapt LuMOS for use with laboratory results assessed on different platforms than used in the trials of belimumab employed to generate the original LuMOS outcome score.1 we calculated a standardized score using z-score transformations. For validation, in each of the Illuminate trials, we calculated LuMOS scores at week 52 for all participants receiving either placebo or one of 2 dosage regimens of TB. Cohen D Effect Size (ES), with 95% confidence intervals (CI), assessed the ability of LuMOS to discriminate between outcomes in active treatment groups versus placebo, and compared it with SRI-5 responder index used in the original trials.
Results LuMOS using standardized z-score transformed laboratory data worked comparably to the original LuMOS model in the analyses of original belimumab trials and was then applied to the Illuminate data sets. LuMOS-based ES for both TB groups in both trials indicated highly significant (p<0.0001), moderately strong treatment effects (ES>0.4), in contrast to weak effects (ES<0.25) based on SRI-5, that were statistically non-significant for Illuminate-1, as reflected by the 95% CI’s that included 0 (table 1).
Comparison of Effect Sizes for TB vs Placebo groups between LuMOS and SRI-5
Conclusion LuMOS improves the ability to detect statistically significant treatment effects. Further validation in SLE trials of non-B cell directed treatments is necessary to document utility as an outcome measure independent of drug mechanism.
Acknowledgement Support from Lupus Research Alliance.
Reference
Abrahamowicz et al. Arthritis Rheumatol. 2018;70:1450-58.
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