Author: Anastasia Madenidou
Schett et al. (0607) followed up 8 SLE patients who received treatment with CD19 CAR T cell therapy. Five patients had a follow-up of more than one year post-CAR T cell infusion. CD19 CAR T cells therapy lead to disappearance of autoantibodies, while vaccination responses remained stable. This observation suggests that the main source of autoantibodies in SLE are CD19+ plasmablasts, which are depleted by CD19 CAR T cells, while antibodies related to vaccination response appear to derive from CD19-negative plasma cells.
Askanase et al. (0608) present the post-hoc analysis of the phase 2 study of cenerimod, an elective sphingosine 1-phosphate (S1P) 1 receptor modulator under investigation for the treatment of SLE (n=427). Cenerimod reduces plasma levels of IFN-α and leads to decreased circulating B and T cells in patients with SLE, suggesting effects on innate and acquired immune responses. The study showed that cenerimod 4 mg led to a greater reduction of disease activity versus placebo at 6 months in patients with baseline high IFN-1 gene expression signature or high anti-dsDNA antibody levels. Cenerimod treatment also reduced the levels of IFN-α protein and anti-dsDNA antibodies in the same patients.
Shipa et al. (0589) have shown in a previous study that serum IgA2 anti-dsDNA antibody levels is a biomarker of response to belimumab after rituximab in SLE (BEAT-lupus trial). Using data from the CALIBRATE trial where 43 patients with lupus nephritis refractory to conventional therapy were randomised to receive either rituximab, cyclophosphamide, and then belimumab (RCB) for 48 weeks, or rituximab and cyclophosphamide (RC), they confirmed that IgA2 anti-dsDNA antibody levels are a predictive biomarker of response to belimumab after rituximab in SLE. Cessation of belimumab therapy after rituximab led to a rise in IgA2 anti-dsDNA antibody levels providing a mechanistic rationale for continuation of therapy.
Sheikh et al. (2347) present the post hoc analysis of pooled data from five belimumab (BEL) trials: BLISS-763 (GSK study BEL110751), BLISS-524 (BEL110752), NEA5 (BEL113750), BLISS-SC6 (BEL112341), and EMBRACE7 (BEL115471; study in patients of self-identified Black race). BEL significantly increased SRI-4 response rates at Week 52 and decreased flares versus placebo in most subgroups by race and ethnicity, which was largely consistent with results from the primary trials. Collectively, this analysis in a large, diverse population of patients with SLE continues to support the efficacy of BEL.
Strand et al. (0582) evaluated the long-term impact of anifrolumab treatment on the Short Form 36 Health Survey version 2 (SF-36v2) in patients from the SLE placebo-controlled, phase 3 long-term extension (LTE) trial. Patients with SLE treated with anifrolumab had sustained improvements in most SF-36v2 individual domains over the 3-year LTE period which supports the long-term benefit of anifrolumab.
Kmetova et al. (1603) evaluated the presence of aPL in a large cohort of critically ill sepsis patients and non-sepsis intensive care unit controls. They found that 23% of critically ill sepsis patients had at least 1 positive aPL, as compared with 9.6% of non-sepsis patients. APL development may be driven by heightened B-cell stimulating signals, and while further mechanistic studies are warranted, some aPL may contribute to improved sepsis survival.
ABOUT THE AUTHOR
Anastasia Madenidou
Anastasia is a Clinical Research Fellow at the University of Manchester, UK. Her major research interests are precision medicine and lupus spectrum disorders.
Anastasia is a member of the Newsletter Sub-Committee and the Deputy Chair of the BSR Trainee Committee.