Background/Purpose: In systemic lupus erythematosus (SLE), organ damage is associated with unfavourable disease courses and premature mortality. We aimed at investigating the impact of organ damage on belimumab treatment efficacy.

Methods: We included 1684 patients with SLE from the BLISS-52 (n=865) and BLISS-76 (n=819) trials. Data were accessed through a data sharing agreement with GSK. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). Disease activity was assessed using the SLEDAI-2K. We evaluated baseline SDI scores as predictors of treatment outcome using logistic regression with SLE responder index (SRI) response at week 52 as the dependent variable. Adjustments for potential confounding factors were performed as appropriate.

Results: When all patients were considered, high baseline SDI scores were associated with a lower chance of attaining SRI response (OR: 0.88, 95% CI: 0.81-0.95; P=0.002). In multivariate analysis, a high baseline SDI score was an independent predictor of non-response, as was long disease duration, whereas high baseline disease activity and high baseline prednisone dose independently predicted SRI response (Figure). We observed the same association between high baseline SDI scores and non-response at week 52 in patients who received belimumab (1 mg/kg or 10 mg/kg; n=1122) (OR: 0.88, 95% CI: 0.79-0.97; P=0.007). High SDI scores independently reduced the probability of response, and high baseline disease activity and prednisone dose independently predicted SRI attainment. Interestingly, disease duration was no longer an independent predictor of treatment outcome (Figure). In patients who received standard of care therapy only (n=562), baseline SDI score were not found to impact the treatment outcome (OR: 0.88; 95% CI: 0.76-1.02; P=0.091).

Conclusion: Previous observations of baseline organ damage reducing belimumab efficacy (1) were corroborated. This impact of organ damage on treatment efficacy was not seen in the placebo group, lending support for a treatment-specific effect. The data suggest that belimumab may be expected to be more efficacious in SLE patients with no organ damage established prior to treatment initiation, irrespective of disease duration and activity grade.

References: 1. Parodis I, et al. Autoimmun Rev. 2017; 16: 343-51.