ACR20 - Day 2 Report Save

Saturday was the day 2 with many posters and live sessions at the 2020 Virtual ACR/ARP meeting. Here are a few of my highlights from day two:

Targeting Plasmacytoid Dendritic Cells in Lupus

Abstract 0935 - Phase 2, Randomized, Double-Blind Trial of BIIB059, an Anti-Blood Dendritic Cell Antigen 2 Antibody, in SLE. This plenary presentation by Dr. R Furie presented the results of Lupus trial using BIIBO59 – a monoclonal antibody that binds to BDCA2 on the surface of plasmocytoid dendritic cells (pDC) – a primary source of type I interferon (IFN). This phase II trial showed that after 24 weeks, BIIBO59 was superior to placebo and significantly improved joint counts, SRI-4 responses and CLASI-50 response – thus proving its benefits in joints and skin outcomes.  Other lupus organ outcomes were not assessed in this trial.  Adverse events were mild to moderate and not unexpected.  Future studies are planned.

Withdrawing Methotrexate or Etanercept in RA Remisssion

Abstract 0939. Maintenance of Remission after Withdrawal of Etanercept or Methotrexate in Patients with Rheumatoid Arthritis in Sustained Remission on Combination Therapy: Results from a Randomized, Double-blind, Controlled Trial.  This plenary session presentation by Dr. Jeff Curtis garnered a lot of discussion.  Patients in SDAI remission on MTX and etanercept (ETN) were either continued, or had MTX or ETN withdrawn.  After 48 weeks, not surprisingly, SDAI remission (without worsening) was seen in 52.9% of continued MTX/ETN, 49.5% of ETN only and 27.8% of those who just continued MTX. These suggest a significant advantage of withdrawing MTX and remaining on ETN only – superior to the withdrawal of ETN and staying on MTX only.  Almost all patients who required rescue therapy were able to recapture LDAS or remission status. 

Novel Compound in Lupus

Abstract 0987. Efficacy and Safety of Iberdomide in Patients with Active Systemic Lupus Erythematosus: 24-Week Results of a Phase 2, Randomized, Placebo-Controlled Study. Dr. Joan Merrill presented this novel intervention – iberdomide a high affinity cereblon ligand that promotes ubiquitination and degradation of transcription factors leading to downregulation of B cells, pDCs, IFN, etc.  The primary endpoint was met with an SRI-4 response at week 24. More research is needed on this potential compound. 

IL-16 as a Urinary Biomarker for Lupus Nephritis

Abstract 0936. Urine Proteomics and Single Cell Transcriptomics Identify IL-16 as a Biomarker for Lupus Nephritis. Another plenary presentation by Dr. Andrea Fava demonstrated the novel use of urine proteomics to demonstrate the utility of IL-16 as a biomarker for renal disease in lupus.  Dr. Fava noted the limitations of urine protein quantification and the invasiveness of renal biopsy, thereby making urine proteomic biomarkers a great advantage if they were able to predict active intrarenal activity.  Proteomics were performed on 112 longitudinal urine samples from 30 SLE patients with active lupus nephritis and 7 healthy controls.  Results were correlated with renal biopsy findings in lupus patients. They found that proliferative lupus nephritis (class III or IV) had a strong correlation with urinary IL-16. Urinary IL-16 correlate with histologic activity  scores (r=0.69), but not with chronicity scores. Moreover, IL-16 concentration was independent of the amount of proteinuria and changed with time as patient activity changed.  Further evidence was shown with IL-16 staining within and about the glomerulus. IL-16, a CD4 ligand with chemotactic and proinflammatory functions, appears to be one of the most expressed cytokine in lupus nephritis and urine IL-16 levels appear to predict renal histological activity.