Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab

Ioannis Parodis; Julius Lindblom; Alexander Tsoi; Leonardo Palazzo; Karin Blomkvist Sporre; Yvonne Enman; Dionysis Nikolopoulos; Lorenzo Beretta

doi:10.1093/rheumatology/keae575

Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab

Rheumatology (Oxford). 2024 Oct 16:keae575. doi: 10.1093/rheumatology/keae575. Online ahead of print.

Authors

Ioannis Parodis^{1

2}, Julius Lindblom¹, Alexander Tsoi¹, Leonardo Palazzo¹, Karin Blomkvist Sporre^{1

3}, Yvonne Enman^{1

3}, Dionysis Nikolopoulos¹, Lorenzo Beretta⁴

Affiliations

¹ Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
² Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
³ Swedish Rheumatism Association, Stockholm, Sweden.
⁴ Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy.

PMID: 39412507
DOI: 10.1093/rheumatology/keae575

Abstract

Objective: Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design.

Methods: Patients with ≥2 visits and available data on SLEDAI-2K, BILAG, PGA, FACIT-F, and glucocorticoid use were included in a post-hoc analysis of four randomised controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes.

Results: Among 2868 patients analysed, baseline median disease duration was 4.5 (IQR: 1.5-9.7) years and mean (± standard deviation) SDI 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9), and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. LLDAS and DORIS remission attainment associated with latent classes.

Conclusion: By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalising treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

Keywords: belimumab; disease activity; disease trajectories; patient-reported outcomes; randomised clinical trial; systemic lupus erythematosus.