February 2025

Opportunities and limitations of B bell depletion approaches in SLE

Nature Review Rheumatol, 2025;21:111–126 DOI: 10.1038/s41584-024-01210-9

Stockfelt et al. reviewed the long-term efficacy and challenges of B cell depletion strategies in SLE. Rituximab, a CD20-targeting monoclonal antibody, has demonstrated efficacy in a subset of patients but remains limited by immunogenicity, residual B cells, and B-cell activating factor (BAFF)-mediated relapse. Newer strategies incorporating CAR T cells, bispecific T cell engagers, and combination therapies aim to enhance B cell depletion and optimise outcomes.

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Efficacy and safety of obinutuzumab in active lupus nephritis

NEJM, 2025. Epub ahead of print. DOI: 10.1056/NEJMoa2410965

Furie et al. demonstrated that obinutuzumab plus standard therapy significantly improved complete renal response at Wk76 compared with placebo. No unexpected safety signals were identified, though infections and COVID-19-related events were more frequent in the obinutuzumab group.

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Belimumab versus telitacicept in sequential treatment after rituximab for refractory lupus nephritis: A real-world multicentre study

Lupus Science & Medicine, 2025;12:e001296 DOI:10.1136/lupus-2024-001296

Chen et al. demonstrated that sequential treatment with belimumab or telitacicept following rituximab (RTX) is a potential therapeutic approach for treating refractory LN. Major AEs included immunoglobin deficiency, respiratory tract infections and urinary tract infections, which are consistent with previous studies.

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January 2025

The 2024 APLAR consensus on the management of lupus nephritis

International Journal of Rheumatic Diseases; 28:e70021 DOI: 10.1111/1756-185X.70021

Mok et al. provided updated consensus recommendations from APLAR, emphasising evidence-based guidance for managing lupus nephritis in Asian populations. These recommendations consider ethnic, socioeconomic, and pharmacogenetic factors, focusing on treatment regimens, adjunctive therapies, and patient-specific approaches to optimise outcomes.

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Association of lupus low disease activity state and remission with reduced organ damage and flare in systemic lupus erythematosus patients with high disease activity

Rheumatology 2024; Epub ahead of print DOI: 10.1093/rheumatology/keae631

Kandane-Rathnayake et al. demonstrated that achieving Lupus Low Disease Activity State (LLDAS) or remission in patients with high disease activity status (HDAS) significantly reduces the risk of organ damage accrual and flares. However, HDAS was found to be a poor prognostic indicator as fewer patients with HDAS attained and sustained LLDAS or remission when compared with non-HDAS patients.

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December 2024

Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: A propensity analysis of the AURA-LV and AURORA 1 studies and ALMS

Lupus Science & Medicine 2024;11:e001319 DOI: 10.1136/lupus-2024-001319

Dall’Era et al. conducted a propensity analysis to compare voclosporin-based triple immunosuppressive therapy with high-dose GC-based regimens for active LN. Voclosporin showed fewer AEs, improved safety, and significantly reduced proteinuria over six months, suggesting a superior risk-benefit profile for patients with lupus nephritis.

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Cenerimod, a sphingosine-1-phosphate receptor modulator, versus placebo in patients with moderate-to-severe systemic lupus erythematosus (CARE): an international, double-blind, randomised, placebo-controlled, phase 2 trial

Lancet Rheumatol. 2024. Epub ahead of print. DOI: 10.1016/S2665-9913(24)00246-7

Askanase et al. assessed the efficacy, safety, and tolerability of cenerimod in patients with moderate-to-severe SLE. While the primary endpoint of reducing mSLEDAI-2K scores at Month 6 was not achieved, cenerimod 4.0mg showed a significant reduction in disease activity versus placebo. Adverse events, including lymphopenia, were dose-dependent but manageable, and overall treatment was well tolerated.

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November 2024

Efficacy and safety of sodium-glucose co-transporter 2 inhibitors for the primary prevention of cardiovascular, renal events and safety outcomes in patients with systemic lupus erythematosus and comorbid type 2 diabetes: A population-based target trial emulation

Arthritis Rheumatol 2024. Epub ahead of print DOI: 10.1002/art.43037

Ma et al. assessed the efficacy and safety of sodium-glucose co-transporter 2 inhibitors (SGLT2i) compared with dipeptidyl peptidase 4 inhibitors (DPP4i) in preventing cardiovascular and renal events in patients with both SLE and type 2 diabetes (T2D). SGLT2i use significantly reduced risks for acute kidney injury, chronic kidney disease, end-stage renal disease, and heart failure, though it increased genital infection risk.

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Effect of iberdomide on cutaneous manifestations in systemic lupus erythematosus: a randomized phase 2 clinical trial

JAAD. 2024. Epub ahead of print DOI: 10.1016/j.jaad.2024.09.074

Werth et al. demonstrated that iberdomide significantly improved cutaneous lupus erythematosus (CLE) outcomes, particularly in subacute and chronic CLE patients, by reducing Cutaneous Lupus Area and Severity Index Activity (CLASI-A) scores. The study showed continued efficacy through 24 weeks, with the 0.45 mg dose providing the greatest improvement in patients with severe baseline scores, and iberdomide was well-tolerated over 104 weeks.

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October 2024

Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first-in-patient, randomised, double-blind, phase I/II study in systemic lupus erythematosus

RMD Open 2024;10:e004701 DOI 10.1136/rmdopen-2024-004701

Tanaka et al. conducted a phase I/II study to evaluate the safety, pharmacokinetics, biomarker response, and efficacy of E6742, a dual antagonist of Toll-like receptors 7 and 8, in patients with systemic lupus erythematosus (SLE). The treatment demonstrated a favourable safety profile, with no serious adverse events, while effectively suppressing interferon gene signatures and showing promising preliminary efficacy.

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