The following is a summary of “Identification of biomarkers to stratify response to B-cell-targeted therapies in systemic lupus erythematosus: an exploratory analysis of a randomised controlled trial,” published in the January 2023 issue of Rheumatology by Shipa, et al.

Lupus erythematosus, or Systemic lupus erythematosus (SLE), is a multifaceted autoimmune disorder characterised by extensive immunological dysregulation and a wide range of clinical manifestations. Possible differential associations between immune system problems and organ involvement or response to targeted therapy are discussed. Specifically, they wanted to find biomarkers of response to belimumab following rituximab so that they could tailor treatment to the individual. Here, they conducted an exploratory analysis of a randomised controlled study (BEAT-LUPUS) that followed 52 patients with SLE as they were treated with either rituximab plus belimumab or rituximab plus placebo.

Researchers employed both machine learning and traditional statistical methods to examine key laboratory and clinical indicators linked with major therapeutic responses. BEAT LUPUS has concluded and is listed as ISRCTN, 47873003. 52 individuals were enrolled in BEAT-LUPUS between February 2, 2017, and March 28, 2019, but only 44 patients supplied 52 weeks of clinical data for this study. Of the total 44 participants, 21 (48%) were assigned to the belimumab group (mean age=39.5 years [SD=12.1]; 17 (81%] were female, 4 (19%) were male, and 13 (62%) were White), while 23 (52%) were assigned to the placebo group (mean age=42.1 [SD=10.5]; 21 (91%) were female, 2 (9%) were male, and 16 (70%) were White). At 52 weeks, 10 (48%) of 21 people who received belimumab after rituximab and 8 (35%) of 23 people who received placebo after rituximab had a substantial clinical response (difference between groups: 13% [95% CI -15 to 38]). Major clinical response to belimumab following rituximab was 48% (95% CI 10 to 70) higher in patients with elevated baseline serum IgA2 anti-double stranded DNA (dsDNA) antibody concentrations, suggesting a predictive connection between these two variables. 

Further, only in the belimumab group did serum IgA2 anti-dsDNA antibody concentrations significantly drop from baseline in individuals with a major clinical response. Reductions in circulating IgA2 plasmablasts (but not total plasmablasts) and T follicular helper cells were observed only in individuals who responded to belimumab following rituximab, and both were predictive of clinical response. Additionally, serum IgA2 anti-dsDNA antibody concentrations were related to renal disease activity, while serum IgA1 anti-dsDNA antibodies were related to mucocutaneous disease activity but did not predict response to B-cell targeted therapy. Regardless of treatment, patients with a high serum interleukin-6 concentration at baseline had a lower chance of a significant clinical response. Precision targeting of advanced therapeutics for this heterogeneous disease may be possible thanks to the identification in this exploratory study of different genetic networks linked with renal and mucocutaneous involvement, as well as response to B-cell-targeted medicines.