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Multicenter Study
. 2025 Jul 1;12(2):e001633.
doi: 10.1136/lupus-2025-001633.

Comorbidity clusters and their relationship with severity and outcomes of index diseases, in a large multicentre systemic lupus erythematosus cohort

Iñigo Rua-Figueroa  1   2 , Natalia Pérez-Veiga  3 , Esther Rodríguez-Almaraz  4 , María Galindo-Izquierdo  5 , Celia Erausquin  6 , Antonio Fernandez-Nebro  7 , Esther Uriarte Itzazelaia  8 , Belén Serrano-Benavente  9 , Jaime Calvo Alén  10 , Sara Manrique-Arija  11 , Jose M Senabre  12 , Jose A Bernal  13 , Javier Narvaez  14 , Eva Tomero  15 , Elena Aurrecoechea  16 , Mónica Ibáñez-Barceló  17 , Vicente Torrente Segarra  18 , Clara Sangüesa  19 , Mercedes Freire-González  20 , María Jesús García-Villanueva  21 , Víctor Martínez Taboada  22 , Marta Arevalo  23 , Claudia Moriano Morales  24 , Carlota Iñiguez  25 , Ana Perez  26 , Eva Salgado  27 , Irene Carrión-Barberà  28 , Jose L Andreu  29 , Tatiana Cobo  30 , Loreto Horcada  31 , Gema Bonilla  32 , Nuria Lozano-Rivas  33 , Lorena Exposito  34 , Carlos Montilla  35 , Francisco J Toyos  36 , Oihane Ibarguengoitia-Barrena  37 , Elia Valls Pascual  38 , Javier Nóvoa Medina  39 , Raúl Menor-Almagro  40 , Jose Andrés Roman Ivorra  41 , Alejandro Muñoz Jiménez  42 , Joan M Nolla  43   44 , Jose Maria Pego-Reigosa  45
Affiliations
Multicenter Study

Comorbidity clusters and their relationship with severity and outcomes of index diseases, in a large multicentre systemic lupus erythematosus cohort

Iñigo Rua-Figueroa et al. Lupus Sci Med. .

Abstract

Objective: Patients with SLE have a well-known increased risk of major comorbidities, although they are also very heterogeneous in terms of the prevalence of comorbid conditions. The relationships of such comorbidities with the outcomes and the severity of index diseases are less known. We aimed to evaluate the interactions between comorbid conditions, in a large multicentre SLE cohort, and their impact on severity and outcomes, using a cluster analysis.

Methods: Data on 14 cumulative comorbidities were derived from patients with SLE (American College of Rheumatology (ACR)-97 criteria) who had been included in the retrospective phase of the RELESSER (Spanish Society of Rheumatology National Register of SLE). The Severity Katz Index and the SLICC/ACR Damage Index were calculated. Unsupervised cluster analysis was performed to better characterise the relationships between comorbidities in a large multicentre cohort of patients with SLE. For intercluster differences testing, analysis of variance and Tukey tests were used to compare continuous numerical variables; a Kruskal-Wallis test to discrete variables and the χ² (or Fisher's exact test) were used for categorical ones.

Results: A total of 3658 patients with SLE were included. Men accounted for 9.6% of patients. The mean (SD) age was 45.9 years, and 93% were Caucasian. Four clusters, with markedly different comorbidity profiles and outcomes, were identified: in cluster 2 (n=516), patients were grouped around depression (100% of the cases); in cluster 3 (n=418) around serious infections (100%); and in cluster 4 (n=388) around cardiovascular events (also 100%). However, in cluster 1, the largest one (n=2336), no patient had any of the three defining comorbidities of the other clusters, and this cluster was associated with the best outcomes.

Conclusions: Cluster analysis identifies well-differentiated subsets of patients with SLE in terms of their comorbidities. The most relevant comorbidities in SLE tend to aggregate in the most severe patient subsets.

Keywords: Cardiovascular Diseases; Epidemiology; Lupus Erythematosus, Systemic.

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Conflict of interest statement

Competing interests: None declared.

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