Elevated interleukin-6 levels predict short-term flare in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by fluctuating activity and unpredictable flares that contribute to cumulative organ damage. Biomarkers capable of identifying patients at risk of near-term disease reactivation are needed. Interleukin-6 (IL-6) has been associated with SLE activity, but its prospective predictive value remains uncertain.

We conducted a prospective, longitudinal, single-center study (2017-2023) including 188 adult with SLE. Serum IL-6 levels were measured at routine and unscheduled visits. Patients were categorized using a prespecified cutoff of 5 pg/mL. Disease activity was assessed using SLEDAI-2K (with values >4 suggesting active disease) and organ-specific manifestations. Prospective (lagged) associations were analyzed using the log-rank test. Discriminative performance was evaluated using ROC analyses and multivariable models adjusted for clinical confounders. IL-6 was compared with anti-double-stranded DNA antibodies and complement components C3 and C4.

During follow-up, 48% of patients had IL-6 levels >5 pg/mL. IL-6 >5 pg/mL was associated with a shorter time to subsequent flare, with a median time to SLEDAI-2K >4 that was 10 months shorter. Elevated IL-6 also predicted arthritis, nephritis, serositis, and hematologic manifestations. Concurrently, IL-6 demonstrated greater discriminative performance than anti-dsDNA, C3, and C4.

Elevated circulating IL-6 levels are associated with short-term disease reactivation in SLE and may complement established biomarkers in longitudinal disease assessment.