Distinct pattern of comorbidities hinders treatment target attainment in SLE through persistent disease activity and...

Remission and low-disease activity are recommended targets in systemic lupus erythematosus (SLE), yet many patients fail to achieve them, underscoring the need to identify contributing barriers. We explored whether comorbidities-some of which share genetic risk with lupus-and their specific patterns influence target accomplishment.

Retrospective cohort of 347 patients with active SLE receiving treatment intensification at inclusion. Comorbidities (n=140), disease activity, treatments and organ damage were monitored (median follow-up 5 years). Mixed-effects assessed relationships between comorbidities and definitions of remission in SLE/lupus low disease activity state (DORIS/LLDAS). Random forests ranked comorbidities according to the strength of associations.

Despite the relatively young age (median 46 years) and short disease duration (median 9 months), patients with SLE exhibited high comorbidity burden (comorbidities count, Rheumatic Disease Comorbidity Index, Elixhauser, Charlson), which increased longitudinally and was associated with reduced attainment of DORIS (ORs: 0.77-0.87, p<0.05) and LLDAS (ORs: 0.74-0.91, p<0.01). Obesity, dyslipidaemia, hypertension, stroke, depression, fibromyalgia and thyroid disorders emerged as the most influential. Presence of ≥1 of these conditions (n=238 [68.6%]) was linked to 55-60% lower likelihood of durable DORIS/LLDAS (≥50% time). Marginal structural models (MSMs) confirmed an independent comorbidities-targets association, regardless of prior achievement, explained by smouldering activity and delayed glucocorticoid tapering. While immunosuppressant/biologic use was comparable, comorbid patients received lower glucocorticoid doses during high disease activity. Comorbidities were also associated with greater damage accrual (IRR: 1.38, 95% CI 1.11 to 1.71), attenuated in patients with sustained DORIS/LLDAS.

Patients with SLE manifest high comorbidity burden, with distinct patterns linked to reduced target attainment. In these patients, vigilant monitoring and treatment adjustments are essential to sustain disease control and prevent damage.