Treat-to-target in SLE: is serology important? Results from an integrated analysis of five randomised clinical trials of belimumab

Alvaro Gomez ^{1, 2}

Julius Lindblom ^{1, 2}

Ioannis Parodis ^{1, 2, 3, 4}

George K. Bertsias ^{5, 6, 7, 8}

Hide authors affiliations Show authors affiliations: 8 affiliations

Karolinska Institutet and Karolinska University Hospital Division of Rheumatology, Department of Medicine Solna, , Stockholm,

Karolinska Institute

Karolinska University Hospital

Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital , Stockholm,

Karolinska Institute

Karolinska University Hospital

Örebro University Department of Rheumatology, Faculty of Medicine and Health, , Örebro, |

⁴

Department of Rheumatology, Faculty of Medicine and Health, Örebro University , Örebro, |

⁵

University of Crete Medical School Rheumatology and Clinical Immunology, , Heraklion, |

⁶

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH) , Heraklion, |

⁷

Rheumatology and Clinical Immunology, University of Crete Medical School , Heraklion, |

⁸

Division of Immunity, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH) , Heraklion, |

Publication type: Journal Article

Publication date: 2025-02-22

Oxford University Press

Rheumatology

scimago Q1

wos Q1

SJR: 1.721

CiteScore: 9.9

Impact factor: 4.4

ISSN: 14620324, 14620332, 14602172

DOI: 10.1093/rheumatology/keaf107

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Abstract

Objectives

DORIS remission, based on clinical activity, and lupus low disease activity state (LLDAS), which includes serological markers, are protective targets in SLE. However, it remains unclear whether their prognostic impact is influenced by serum anti-dsDNA and complement levels

Methods

We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) totalling 45 254 monthly visits. Generalized linear models evaluated the effects of DORIS/LLDAS—with or without active serology—on the risk for severe (BILAG ≥1A/2B) and renal (BILAG A/B) flares. Organ damage was also assessed.

Results

Normal serology occurred in 544/1871 (29.1%) DORIS and 1879/4760 (39.5%) LLDAS visits. Using no-DORIS as reference, DORIS with anti-dsDNA(−) or normal/high C3/C4 demonstrated stronger protection against severe flares (odds ratio [OR] 0.042 [95% CI: 0.005, 0.331] and 0.216 [95% CI: 0.094, 0.494], respectively) compared with DORIS with anti-dsDNA(+) or low C3/C4 (OR 0.511 [95% CI: 0.284, 0.919] and 0.528 [95% CI: 0.261, 1.067]). Similarly, LLDAS with normal serology showed greater risk-reduction in severe flares compared with LLDAS with active serology, especially low C3/C4. For renal flares, DORIS with serological activity carried ∼6-fold higher risk compared with combined clinical/serological remission (OR 5.94 [95% CI: 1.26, 28.04]). Damage accrual was lowest in patients with sustained DORIS and ≥1 visit showing anti-dsDNA(−) (0.8%) or normal C3/C4 (1.8%).

Conclusion

Normal serology enhances the protection of DORIS and LLDAS against severe and renal SLE flares, possible reflecting deeper states of disease control. Patients with recently active disease who meet clinical targets but have persistently abnormal serology may require close monitoring to minimize flare-risk.

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Gomez A. et al. Treat-to-target in SLE: is serology important? Results from an integrated analysis of five randomised clinical trials of belimumab // Rheumatology. 2025.

GOST all authors (up to 50) Copy

Gomez A., Lindblom J., Parodis I., Bertsias G. K. Treat-to-target in SLE: is serology important? Results from an integrated analysis of five randomised clinical trials of belimumab // Rheumatology. 2025.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1093/rheumatology/keaf107

UR - https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keaf107/8030223

TI - Treat-to-target in SLE: is serology important? Results from an integrated analysis of five randomised clinical trials of belimumab

T2 - Rheumatology

AU - Gomez, Alvaro

AU - Lindblom, Julius

AU - Parodis, Ioannis

AU - Bertsias, George K.

PY - 2025

DA - 2025/02/22

PB - Oxford University Press

SN - 1462-0324

SN - 1462-0332

SN - 1460-2172

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2025_Gomez,

author = {Alvaro Gomez and Julius Lindblom and Ioannis Parodis and George K. Bertsias},

title = {Treat-to-target in SLE: is serology important? Results from an integrated analysis of five randomised clinical trials of belimumab},

journal = {Rheumatology},

year = {2025},

publisher = {Oxford University Press},

month = {feb},

url = {https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keaf107/8030223},

doi = {10.1093/rheumatology/keaf107}

}

Publisher

Oxford University Press

Journal

Rheumatology

scimago Q1

wos Q1

SJR

1.721

CiteScore

9.9

Impact factor

4.4

ISSN

14620324 (Print)

14620332 (Electronic)

14602172 (Electronic)