Early SLE may follow a fast comorbidity/multimorbidity trajectory associated with flare burden and glucocorticoid exposure.

Authors

Myrto Nikoloudaki, Sofia Pitsigavdaki, Spyridon Katechis, Ettore Silvagni, Argyro Repa, Antonio Marangoni, Irini Flouri, Nestor Avgoustidis, Prodromos Sidiropoulos, Marcello Govoni, Antonis Fanouriakis, Alessandra Bortoluzzi, Dimitrios Boumpas, George Bertsias

Published in

RMD open. Volume 12. Issue 3. Sep 23, 2026. Epub Sep 23, 2026.

Abstract

Patients with systemic lupus erythematosus (SLE) carry a substantial comorbidity load associated with worse prognosis, yet most evidence pertains to long-standing disease. How comorbidities-particularly multimorbidity as a marker of overall health burden-evolve at early stages, and whether conditions co-aggregate into clinically meaningful clusters, remains unclear.
An inception cohort (≤2 years from diagnosis) of 311 patients with SLE with 5-year monitoring of 140 comorbidities, disease activity, treatments, organ damage and adverse events/hospitalisations. Growth mixture modelling identified trajectories of incident comorbidities, while tetrachoric exploratory factor analysis followed by clustering defined multimorbidity profiles; these trajectories and profiles were then related to longitudinal outcomes. To inform temporal ordering, trajectory modelling was refitted for months 24-60, and predictors from <24 months were evaluated using penalised multivariable regression.
Early SLE separated into slow (55%) and fast (45%) incident-comorbidity trajectories. Among fast accruers, three phenotypes emerged: low-to-moderate (general/non-patterned) (51%), metabolic-psychiatric (31%) and cardiopulmonary-musculoskeletal (18%), with a gradual increase in multimorbidity (≥2 conditions) (32.7%, 65.7% and 100%, respectively). Compared with slow-accruing, fast-accruing patients-especially the metabolic-psychiatric and cardiopulmonary-musculoskeletal-attained less lupus low disease activity state/Definition of Remission In SLE and developed more damage (incidence rate ratio (IRR) 2.28-3.27) and safety-related events (IRR 1.89-3.36). Severe flares (≥20% of time; OR 2.10, 95% CI 1.09 to 4.04) and glucocorticoid exposure (OR 1.06 per 10 mg/day, 95% CI 1.01 to 1.11) during the first 24 months independently predicted subsequent fast-comorbidity trajectory. Flares were more prominent in the fast/low-to-moderate and metabolic-psychiatric phenotypes, whereas glucocorticoid use was more prominent in the cardiopulmonary-musculoskeletal phenotype.
Nearly half of patients with newly diagnosed SLE show accelerated comorbidity and multimorbidity burden, underscoring the need for clinical vigilance. Fast-accrual phenotypes are linked to flares and glucocorticoid exposure, two potentially modifiable features of early disease.

PMID:
42778333
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.

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