Objectives: Development of therapies for systemic lupus erythematosus (SLE) has in part been limited by the lack of suitable outcome measures in clinical trials. In the present post-hoc analysis of two clinical trials of belimumab, we investigated two potential outcomes, the Lupus Low Disease Activity State (LLDAS) and clinical SLE disease activity index 2000 (cSLEDAI-2K) zero, in relation to SLE responder index 4 (SRI-4). Methods: A total of 1684 SLE patients from the BLISS-52 (n = 865) and BLISS-76 (n = 819) trials were surveyed. Physician's Global Assessment (PGA) scores <0.5 (3-point scale) were used for comparisons. We used the chi-square test for comparisons and the phi coefficient for correlations. Results: At week 52, LLDAS was achieved by 8.6% of patients, cSLEDAI-2K = 0 by 34.5% and SRI-4 by 45.1%. cSLEDAI-2K = 0 showed the strongest correlation with PGA <0.5 (rφ = 0.36, P < 0.001). cSLEDAI-2K = 0 unveiled the superiority of belimumab 10 mg/kg over placebo (P = 0.003) with a magnitude which was comparable to that of SRI-4 (P < 0.001). LLDAS displayed a more moderate separation (P = 0.033). Conclusions: LLDAS was a stringent measure. cSLEDAI-2K = 0 showed the strongest correlation with the clinician-based evaluation. Being based on the SLEDAI-2K only, cSLEDAI-2K = 0 may be considered a more pragmatic outcome measure in SLE studies compared with composite tools.
Keywords: Systemic lupus erythematosus; belimumab; biologics; outcome measures; treatment.