SLE Clinical Trial Design and Outcome Measures Save

Clinical trials remain a challenge in SLE and a number of outcome measures have been used with varying success.

Two abstracts in this session sought to address novel ways to assess responses in SLE trials.

Kim et al (abstract 1838) assembled 759 patients from the ‘placebo’ (standard of care-SOC) arms of SLE trials as part of the Collective Data Analysis Initiative (CDAI). To this data they applied multistate Markov models to assess the average duration of response and the total time in response over a 52 week trial period. In this they defined response in several ways based on the SRI (4-6) and BICLA outcome measures. Landmark responses in these SOC patients ranged from 32.5%-45.9% at 52 weeks depending on the precise outcome measure of response. The mean ‘sojourn time’ in the response state varied from 20.4-31.5 weeks with different response definitions. In addition, the total time in a response state ranged from 16.4-24.8 weeks, which is less than half of the follow-up period assessed. Looking at predictors of response these varied according to the definition of response employed. Markers of more severe disease were however associated with shorter times in the response state.

This data suggested that using multistate modelling and assessing the time in a response state may provide better and more comprehensive assessments of the efficacy of interventions in RCTs and may be better able to discriminate active drug from SOC therapies and thus improve the efficiency of SLE clinical trials.

Abrahamowicz et al (abstract 1839) aimed to develop a novel outcome measure for use in SLE trials using a data-driven approach. For development and validation, they used the 2 belimumab trials, BLISS-76 and BLISS-52 as training and validation sets respectively. The Multivariate Lupus Outcome Score (LuMOS) was developed by determining measures that best discriminated between active and SOC arms of the BLISS 76 trial. The LuMOS score derived weighted ‘points’ for a range of measures including a SLEDAI improvement of >4 points, increase C4, a decrease in C3 and anti-dsDNA antibodies, as well as no change in the BILAG renal domain, improvement in the BILAG mucocutaneous domain and a decrease in steroid dose used.

The use of LuMOS revealed better effects size for belimumab vs placebo in the BLISS-76 training set and also when applied to the BLISS-52 trials validation set. Indeed greater effect sizes were also seen for the belimumab 1mg/kg trial arms.

The LuMOS may be a novel approach to assessing outcomes in SLE. A limitation currently is that it remains to be seen whether it is a novel outcomes measure for any SLE therapy or whether it is actually therapy or mechanism specific (anti-Blyss therapy). Further work in other mode of action agents will now be important to determine the place that LuMOS will have in future SLE clinical trials.

Abstract 1838
Abstract 1839
Abstract 1840
Abstract 1841
Abstract 1842
Abstract 1843