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

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