August 2025 to November 2025
Author: Maxime Melchior
Effects of Long-Term Ixazomib on Bone Mass in Multiple Myeloma
Levring et al. (10.1016/j.bone.2025.117660) investigated the impact of ixazomib (an oral proteasome inhibitor) on bone disease in patients with multiple myeloma in remission over a 24-month period. The results revealed that short-term treatment (3 months) induces bone anabolism with an increase in trabecular bone volume, followed by a long-term effect (3 to 24 months) that improves bone mineralization and structural strength. Overall, treatment with ixazomib improves bone mass and strength and may prevent new skeletal-related events.
Safety and Efficacy of Allogeneic CD19 CAR NK-Cell Therapy in SLE
Gao et al. (10.1016/S0140-6736(25)01671-X) reported on a first-in-human case series using allogeneic CD19 CAR NK-cells for refractory systemic lupus erythematosus. The therapy achieved deep B-cell depletion and induced DORIS remission or low disease activity in 67% of patients after 12 months. The safety profile was encouraging with only 1/18 case of grade 1 cytokine release syndrome, no neurotoxicity, and no severe infections. This approach could address manufacturing and safety barriers currently observed in autologous CAR T-cell therapy.
Nipocalimab as a Targeted Therapy for Moderate-to-Severe Sjögren’s Disease
Noaiseh et al. (10.1016/S0140-6736(25)01430-8) evaluated nipocalimab, a neonatal Fc receptor blocker, in a phase 2 trial for Sjögren’s disease. The 15 mg/kg dose led to a significant reduction in ClinESSDAI scores at week 24 compared to placebo. Nipocalimab effectively induced dose-dependent reductions in total IgG, anti-Ro60, anti-Ro52 and anti-La levels. This study provides evidence that targeting IgG clearance is a promising approach for the management of Sjogren’s disease.
Telitacicept for the Treatment of Active Systemic Lupus Erythematosus
van Vollenhoven et al. (10.1056/NEJMoa2414719) conducted a phase 3 trial assessing Telitacicept, a dual BLyS/APRIL inhibitor, in Chinese patients with active SLE in addition to standard of care. At week 52, 67.1% of patients receiving telitacicept achieved a modified SRI-4 response, significantly higher than the 32.7% in the placebo group. In contrast to previous Atacicept trial no signal of increased serious adverse events were observed, but only higher rates of upper respiratory tract infections, decreased immunoglobulin levels, and injection-site reactions. These results encourage conduction of RCT in other populations and suggest the usefulness of this therapeutic approach.
Loss-of-Function PLD4 Mutations as a Genetic Cause of Monogeneic SLE
Wang et al. (10.1038/s41586-025-09513-x) published a great example of translational research in rheumatology. After identifying biallelic loss-of-function mutations in PLD4 in five patients with systemic lupus erythematosus, they studied the role of PLD4, highlighting that its deficiency leads to impaired nucleic acid degradation, causing overactivation of TLR7/9 and the type I interferon pathway. This genetic defect results in cell-intrinsic expansion of plasmacytoid dendritic cells and plasma cells. Remarkably, the JAK inhibitor baricitinib successfully rescued the autoimmune phenotype in both mouse models and patient cells.
Maxime Melchior
Maxime is a Rheumatologist and PhD fellow at the Université Libre de Bruxelles Center for Research in Immunology (U-CRI), where he conducts fundamental and translational research on spondyloarthritis and associated diseases. His research aims to decipher the role of genetic risk factors in shaping T cell dysfunction in these conditions. Maxime is a member of the Belgian Society of Rheumatology’s Young Rheumatologists Working Group (NextGen Academy – SRBR/KBVR) and a member of the EMEUNET Newsletter Sub-Committee.