May 2025

Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria

RMD Open 2025;11:e005-444 DOI:10.1136/rmdopen-2025-005444

Padrodis et al. aimed to determine belimumab efficacy assessed using BICLA in patients with SLE included in the phase III belimumab RCTs. The benefit of belimumab was found to be more prominent when combined with anti-malarial agents. Furthermore, using BICLA, the authors validated the results from foundational trials originally assessing belimumab efficacy using SLE Responder Index 4 thus, corroborating the efficacy of #belimumab in SLE.

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Long-term effect of anifrolumab on patient-reported outcomes in systemic lupus erythematosus (TULIP-LTE): a randomised, placebo-controlled, phase 3 long-term extension trial

Lancet Rheumatol, 2025 DOI 10.1016/S2665-9913(25)00022-0

Strand et al. performed an exploratory analysis to assess patient-reported outcome measures, to investigate how patients with moderate-to-severe SLE perceive the effects of long-term treatment with #anifrolumab on their health status and health-related quality of life. They report improvements in health status and health-related quality of life, including differences favouring anifrolumab compared with placebo. These numerical improvements in patient- reported outcomes occurred alongside improvements in disease activity, reduced glucocorticoid doses, and a tolerable safety profile. These data suggest that anifrolumab is an effective treatment option that might improve health-related quality of life.

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April 2025

Unsupervised machine learning identifies distinct systemic lupus erythematosus patient endotypes with differential response to belimumab

Rheumatol (Oxford), 2025 DOI: 10.1093/rheumatology/keaf215. Epub ahead of print

Depascale et al. used unsupervised machine learning to identify three SLE endotypes based on B cell immunophenotyping and serological profiles. Belimumab was most effective in patients with transitional and naïve B cell enrichment (Cluster 2), where it significantly increased the likelihood of achieving sustained LLDAS and DORIS remission.

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March 2025

LLDAS and remission attainment with anifrolumab treatment in patients with systemic lupus erythematosus: results from the TULIP and long-term extension randomised controlled trials

Ann Rheum Dis. 2025:S0003-496700071-8. DOI: 10.1016/j.ard.2025.01.016. Epub ahead of print

Morand et al. conducted a post-hoc analysis of the phase III TULIP-1 and TULIP-2 trials and their long-term extension, including 369 patients with moderate to severe SLE, to evaluate the long-term impact of anifrolumab on attainment of LLDAS and DORIS-defined remission. The results demonstrated that anifrolumab significantly improved the likelihood, speed, and duration of LLDAS and DORIS remission versus placebo over 4 years, with benefits sustained throughout the treatment period.

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Belimumab efficacy in mucocutaneous lupus erythematosus: a large post-hoc analysis from five phase III clinical trials

Rheumatol, 2025. Epub ahead of print. DOI: 10.1093/rheumatology/keaf145

Grosso et al. conducted a post-hoc analysis of five phase III trials, including 3086 patients, to evaluate the efficacy of belimumab in improving mucocutaneous manifestations of SLE. The results demonstrated that belimumab significantly improved disease activity as measured by the mcBILAG and mcSLEDAI-2K indices compared with placebo and reduced flare rates in patients with high disease activity and serological positivity.

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Evolution and trajectory of B-cell targeted therapies in rheumatic diseases

Lancet Rheumatol, 2025. Epub ahead of print

Carter et al. review the clinical and mechanistic development of B-cell targeted therapies over the last two decades in autoimmune rheumatic diseases. B-cell depletion depth, repopulation dynamics, and immunogenicity determine long-term efficacy and inform the rationale for emerging
dual-targeted approaches, particularly in systemic lupus erythematosus where belimumab and rituximab combinations show potential to mitigate relapse driven by BAFF.

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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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