Weekly Spotlight - 03.10.24

In the News

New Model Predicts Lupus Activity with Blood Cell Parameters

This study offers a promising new approach to evaluating disease activity in patients with systemic lupus erythematosus (SLE) by focusing on specific blood cell parameters. Researchers found that the standard deviation of lymphocyte volume (SD-V-LY), red blood cell (RBC) count, and lymphocyte percentage (LY) are key indicators of SLE activity. By employing machine learning, they developed a prediction model that demonstrated high accuracy and sensitivity, making it a valuable tool for clinicians. This model, which is both cost-effective and user-friendly, could significantly improve the management and treatment of SLE, particularly in grassroots medical institutions.

The findings highlight the importance of SD-V-LY, RBC count, and LY in reflecting disease activity and their potential as reliable biomarkers. The study also underscores the need for further validation in larger, multicentre studies to confirm these results. Overall, this research provides hope for better disease monitoring and management, ultimately aiming to reduce organ damage and improve the quality of life for patients with SLE.

CD38's Role in SLE T Cells and IL-2 Suppression

CD38 has been identified as a promising therapeutic target for patients with systemic lupus erythematosus (SLE). This study reveals that CD38 alters the lipid profile of CD4 T cells, shifting gangliosides from GM3 to GM2, which in turn increases calcium flux and endoplasmic reticulum stress. This process suppresses interleukin-2 (IL-2) production, a crucial cytokine for immune function. By inhibiting CD38, either through biologics or small drugs, there is potential to restore IL-2 production and improve patient outcomes.

The findings highlight the importance of targeting CD38 to manage SLE more effectively. The study suggests that controlling calcium homeostasis and lipid composition in CD4 T cells can alleviate some of the disease's symptoms. This research offers hope for new treatment strategies that could significantly benefit those suffering from SLE, providing a clearer path towards better disease management and improved quality of life for patients.

Promising B-cell Therapies for Lupus Show Positive Results

Obinutuzumab and ianalumab are emerging as promising B-cell depleting therapies for lupus, according to recent data presented at the 2024 Congress of Clinical Rheumatology West. Dr Richard A. Furie, chief of rheumatology at Northwell Health, expressed optimism about these developments, highlighting obinutuzumab's enhanced potency and its significant impact on lupus nephritis in the NOBILITY phase 2 trial. The drug demonstrated profound B-cell depletion and sustained renal response, with positive outcomes in the phase 3 REGENCY study.

Ianalumab, another promising therapy, targets both B cells and the B-cell activating factor pathway. Initially showing effectiveness in a Sjögren's trial, ianalumab also yielded significant results in a small phase 2 study for systemic lupus erythematosus. Dr Furie noted its profound impact on the SLE Responder Index 4 response, with ongoing trials for both SLE and lupus nephritis. These advancements suggest a hopeful future for lupus treatment, potentially leading to better patient outcomes.

Promising Results for New Lupus Treatment in Phase III Trials

UCB and Biogen have shared encouraging Phase III clinical trial results for dapirolizumab pegol, a promising treatment for moderate-to-severe systemic lupus erythematosus (SLE). The PHOENYCS GO study demonstrated significant improvement in disease activity at week 48, using the BILAG-based BICLA measurement. This new drug works by inhibiting the CD40L protein, thereby reducing harmful autoantibody production. The trial, which was multicentre, randomised, double-blind, and placebo-controlled, showed that dapirolizumab pegol not only reduced disease activity but also decreased the frequency of disease flares.

Following these positive results, UCB and Biogen plan to launch a second Phase III study, PHOENYCS FLY, in 2024. Additionally, participants from the PHOENYCS GO study will be monitored over a longer period in an open-label study. This continued research aims to provide further insights and hope for those affected by SLE. For ongoing updates on lupus treatments and clinical trials, stay connected with the Lupus Foundation of America.

Understanding X Chromosome Inactivation in Systemic Lupus Erythematosus

Recent research has delved into the connection between X chromosome inactivation and systemic lupus erythematosus (SLE), a condition more prevalent in women. The study examined blood samples from 181 individuals with SLE, revealing that those with lupus exhibited less X chromosome inactivation compared to healthy individuals. Interestingly, this skewing was more pronounced in cases involving renal disease and less common in those under 40, suggesting that X chromosome inactivation is a result of SLE rather than its cause.

These findings challenge previous assumptions and highlight the need for further research into the multiple factors contributing to autoimmune diseases. Scientists suggest that future studies should explore various pathways and mechanisms beyond just X chromosome inactivity. This comprehensive approach could provide a clearer understanding of why women and men are differently affected by autoimmune conditions, offering hope for more effective treatments and interventions.

Promising Results for Gazyva in Lupus Nephritis Treatment

Genentech has announced promising results from the Phase III REGENCY study of Gazyva (Obinutuzumab) for treating lupus nephritis (LN). This engineered monoclonal antibody targets CD20 proteins on B cells, which cause kidney inflammation and damage. The study, involving 271 participants, showed that those receiving Gazyva alongside standard therapy had a higher rate of complete renal response at 76 weeks compared to the placebo group. This breakthrough could potentially prevent or delay the progression to end-stage renal disease, offering new hope for those affected by LN.

Dr. Brad Rovin, a nephrologist and investigator in the study, highlighted the significance of these findings, noting that this is the first Phase III trial of an anti-CD20 B cell depleting drug to show positive results. Gazyva, which has been granted Breakthrough Therapy designation by the FDA, is also being studied for other conditions, including membranous nephropathy and systemic lupus erythematosus. Current data is being shared with health authorities to expedite the availability of this promising treatment.

Promising Results for Gazyva in Lupus Nephritis Treatment

Genentech has announced promising results from the Phase III REGENCY study of Gazyva (Obinutuzumab) for treating lupus nephritis (LN). This engineered monoclonal antibody targets CD20 proteins on B cells, which cause kidney inflammation and damage. The study, involving 271 participants, showed that those receiving Gazyva alongside standard therapy had a higher rate of complete renal response at 76 weeks compared to the placebo group. This breakthrough could potentially prevent or delay the progression to end-stage renal disease, offering new hope for those affected by LN.

Dr. Brad Rovin, a nephrologist and investigator in the study, highlighted the significance of these findings, noting that this is the first Phase III trial of an anti-CD20 B cell depleting drug to show positive results. Gazyva, which has been granted Breakthrough Therapy designation by the FDA, is also being studied for other conditions, including membranous nephropathy and systemic lupus erythematosus. Current data is being shared with health authorities to expedite the availability of this promising treatment.