Evaluating duration of response to treatment in systemic lupus erythematosus clinical trials

OBJECTIVE: To evaluate response duration and identify predictors of transitioning into and out of the response state in patients with SLE receiving standard of care (SoC) in 52-week clinical trials. METHODS: A multistate model (MSM) allowing for bidirectional transitions between response and non-response states was fit to data on 759 patients with SLE with active disease randomised to SoC. The probability of being in response at 52 weeks, average duration of response (sojourn time) and mean total time in response for SLE Responder Index (SRI-4, SRI-5, SRI-6) and BILAG-based Composite Lupus Assessment (BICLA) were estimated. Predictors of attainment and loss of SRI-5 response were also assessed. RESULTS: The MSM estimated probability of being in response at 52 weeks ranged from 42% (SRI-6) to 61% (SRI-4). Mean duration of response ranged from 20.4 weeks (BICLA) to 31.5 weeks (SRI-4). Mean total time in response was 16.4–24.8 weeks. Baseline characteristics predictive of shorter SRI-5 response duration were African descent (p=0.005), longer history of disease (p=0.03), higher anti-dsDNA antibody titres (p=0.039), lower lymphocyte count (p=0.008) and lower haemoglobin (p=0.006). Younger age (p<0.001) and higher protein/creatinine ratio (p<0.001) were associated with higher likelihood of achieving SRI-5 but also shorter response duration. CONCLUSION: Factors associated with disease severity were more predictive of shorter response duration than of 52-week response status. Analysing landmark response rates and response duration using MSM may be a more powerful way to distinguish effective investigational treatments from background SoC, although this remains to be evaluated in future trials.