Curcumin as a Component Of A Sustainable Gout Control Strategy With Febuxostat: Clinical Outcomes, Systemic Inflammation, And Response Predictors

Abstract

Gout is a systemic metabolic-inflammatory disease characterized by persistent hyperuricemia combined with chronic low-grade inflammation, insulin resistance, and a high comorbidity burden. In real-world outpatient practice, key barriers to long-term control remain variability in the clinical course, early flares at the start of urate-lowering therapy, poor adherence, and persistent systemic inflammatory reactivity. Curcumin is considered a safe anti-inflammatory and metabolically targeted component that potentially enhances the sustainability of the clinical response in gout.

To evaluate the clinical and laboratory efficacy of adding curcumin to urate-lowering therapy with Adenuric in patients with gout and hyperuricemia, and to determine the impact of the combined approach on systemic inflammation, metabolic profile, quality of life, and the incidence of concomitant urological complications over 12 months.

A single-center, controlled study was conducted (2021–2025, Urgench outpatient clinic). A total of 312 participants were examined: Group 1 — Adenuric (n=106), Group 2 — Adenuric + curcumin (n=97), and Group 3 — control (n=109). Group 2 underwent follow-up from T0–T3 (3, 6, and 12 months). We assessed uric acid levels (SUA), attack frequency, VAS pain score, CRP, systemic immune-inflammatory index (SII), cytokines (IL-1β, IL-6, IL-38), metabolic profile indicators (HOMA-IR, atherogenic index), EQ-5D, urinary syndrome markers, and urinary tract infection (UTI) frequency. Multivariate logistic regression of UTI recurrence predictors and ROC analysis of prognostic tools (OI-GOUT, ISI-GOUT based on SII, IL-38) were performed.

By the 12th month, combination therapy provided deeper urate control: SUA 322±49 vs. 356±54 μmol/L (p<0.001) and more frequent achievement of the target SUA <360 μmol/L (82.5% vs. 67.9%; p=0.018). Clinical activity of gout was lower in group 2: attack frequency 0 [0;1] vs. 1 [0;2] (p=0.001), VAS pain 2.3±1.2 vs. 3.1±1.4 (p<0.001), the proportion of patients with a reduction in attack frequency ≥50% was 84.5% vs. 70.8% (p=0.020). A more pronounced attenuation of systemic inflammation and strengthening of the regulatory link were noted: SII 560 [410;800] versus 690 [520;980] (p<0.001), CRP 2.6 [1.5;4.8] versus 4.2 [2.3;7.1] (p<0.001), IL-38 69 [54;88] versus 52 [40;66] (p<0.001). Recurrence of UTI within 12 months was less common with combination therapy (9.3% versus 21.7%; p=0.015); In a multivariate model, combination therapy maintained an independent protective effect (OR=0.38; 95% CI 0.16–0.89; p=0.026), and SII (OR=1.34 per +300; p=0.007) and IL-38 (OR=0.82 per +10 pg/ml; p=0.009) were significant predictors of relapse. ROC analysis showed clinically useful discrimination: OI-GOUT for ≥2 attacks/year AUC=0.76 (cut-off ≥20; Se/Sp 72/70%), ISI-GOUT for UTI recurrence AUC=0.74 (cut-off ≥900; 69/68%), IL-38 AUC=0.71 (cut-off ≤45 pg/ml; 66/67%). Metabolic and functional outcomes at T3 were better in Group 2: HOMA-IR 2.6±1.0 vs. 3.1±1.1 (p=0.002), atherogenic index 3.4±0.8 vs. 3.9±0.9 (p<0.001), EQ-5D 0.82±0.11 vs. 0.76±0.12 (p<0.001). The safety profile was comparable (p>0.05 for major adverse events).

The addition of curcumin to Adenuric therapy is associated with more pronounced control of hyperuricemia and clinical gout activity, a reduction in systemic inflammation with an increase in IL-38, an improvement in the metabolic profile and quality of life with comparable tolerability. The SII/IL-38 indices and the integral OI-GOUT and ISI-GOUT indices demonstrate prognostic value for early risk stratification and monitoring of therapy response.