Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials.

Abstract

The Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) international task force has proposed remission definitions that are amenable to scientific testing. In this study, we aimed to evaluate their suitability as outcome measures in studies of systemic lupus erythematosus. In this post-hoc study, we applied remission definitions as specified by DORIS criteria at multiple timepoints in the BLISS-52 (n=865) and BLISS-76 (n=819) clinical trials. All definitions required physician's global assessment scores less than 0·5 (possible range 0-3). The DORIS 1 definitions required clinical systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K)=0 (with serological items excluded). The DORIS 2 definitions required a score of D or E in all British Isles Lupus Assessment Group (BILAG) domains. The definitions were assessed in the trial populations both with (on therapy) and without (off therapy) treatment allowance-ie, low-dose glucocorticoids (prednisone ≤5 mg/day) and maintenance immunosuppressive and biological agents. Antimalarial agents were allowed in all definitions. The definitions were applied irrespective of serological activity (anti-double stranded DNA positivity, or low C3 or C4) and with normal serology. Finally, we applied modifications similar to DORIS on therapy but allowing higher prednisone doses (≤10 mg/day). In the pooled dataset, the remission definition most frequently attained was the modified (prednisone ≤10 mg/day) DORIS 1a on therapy definition, which required a SLEDAI-2K score of 0 and permitted serological activity (237 [17·8%] of 1333 participants at week 52), followed by the unmodified (predisone ≤5 mg/day) DORIS 1 on therapy definition (140 [10·5%] of 1336 participants at week 52) based on these two definitions. We detected no significant difference between the placebo and belimumab groups. Proportions of patients achieving off therapy and BILAG-based definitions were low (≤0·9% at all timepoints). Sustained attainment of certain on therapy definitions showed an ability to discriminate between patients who received belimumab 10 mg/kg and patients who received placebo. Attainment of DORIS remission definitions was infrequent overall. Use of clinical SLEDAI-2K=0 in the definitions yielded higher proportions of attainment than did use of BILAG D or E. Attainment was also higher using definitions that allowed for serological activity and maintenance treatment. Addition of the durability aspect to on therapy definitions led to an ability to discriminate between belimumab and placebo. Swedish Rheumatism Association, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet Foundations.