Article Text
Abstract
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.
- systemic lupus erythematosus
- disease activity
- treatment
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Footnotes
Collaborators Bevra Hahn, MD; Jan Hillson, MD; Jane Salmon, MD; Nathalie Franchimont, MD, PhD; Neil Solomons, MD; Paul Brunetta, MD; Richard Furie, MD; Robert Hoffman, DO; Sabine Bongardt; Stephen Wax, MD; Tim Behrens, MD.
Contributors MK, JTM, KK and PI contributed to the study design, statistical analysis and interpretation of results. LH contributed to the acquisition of data. All authors reviewed and approved the final manuscript.
Funding This work was supported by a grant from the Lupus Foundation of America.
Competing interests KK received consulting fees from Eli Lilly; MK received consulting fees from Celgene.
Patient consent Not required.
Ethics approval In accordance with the policy of our institution, ethical approval from our Research Ethics Board for this type of study was not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Please contact the Lupus Foundation of America for access to the Collective Data Analysis Initiative database.