MF Del Pino Zambrano , P Cardoso Peñafiel, C Marín Huertas, L Cebrián Méndez, L Lojo Oliveira, A Pareja Martinez, A Román Pascual, O Sánchez González, C Siso Hernández, S Cruz Beltran, Mt Navío Marco, E Calvo Aranda
Affiliation(s):
Servicio De Reumatologia Hospital Universitario Infanta Leonor
Introduction: Tophaceous gout that is refractory or intolerant to conventional uratelowering therapy (ULT) and IL1 blockade remains a therapeutic challenge. Interleukin6 (IL6) is involved in the inflammatory cascade of gout, and its inhibition with tocilizumab (TCZ) may offer an alternative option in selected patients with contraindications to standard treatment.
Objective: To describe the clinical effectiveness, laboratory changes and safety of subcutaneous (s.c.) TCZ in patients with difficulttotreat (D2T) tophaceous gout and prior inadequate response or intolerance to anakinra.
Method: This singlecentre retrospective descriptive study included all adults with crystalproven tophaceous gout who received TCZ on a compassionate basis between 2018 and 2025. Eligibility criteria were ≥3 flares/year and/or intolerance or contraindication to standard ULT, failure or intolerance to anakinra, and at least one dose of TCZ (162 mg every 1 week). Demographic and clinical data, comorbidities, number of attacks in the previous 12 months, prior therapies, and laboratory parameters [serum urate (SU), Creactive protein (CRP), estimated glomerular filtration rate (eGFR)] were collected at baseline and at 3, 6 and 12 months when available. Paired ttests were used exploratorily given the small sample size to compare baseline with followup values.
Results: Six male patients were included (mean age at TCZ initiation 57.8±16.3 years, mean gout duration 20.3±14.3 years; all with extensive tophaceous disease). The mean number of attacks in the 12 months preceding TCZ was 6.7±2.4. All patients had received colchicine and systemic glucocorticoids (3/6 had prior NSAID treatment) and were treated with febuxostat at the maximal tolerated dose (mean 100±22 mg/d) and anakinra (100 mg/d; median 5 doses, range 2–9) with inadequate response. Comorbidities included hypertension (4/6), dyslipidaemia (4/6), diabetes mellitus (1/6) and chronic kidney disease stage 3 (1/6). Baseline mean SU was 6.6±2.8 mg/dL; mean values at 3, 6 and 12 months were 5.2±2.5, 9.5±3.1 and 3.3±0.6 mg/dL, respectively. In paired analyses, differences in SU did not reach statistical significance at 3 months (n=5, 6.0 vs 5.2 mg/dL, p=0.49) or 6 months (n=3, 7.6 vs 9.5 mg/dL, p=0.34), while a nonsignificant trend towards lower SU was observed at 12 months (n=3, 7.6 vs 3.3 mg/dL, p=0.06). Mean CRP decreased from 93.9 mg/L at baseline to 1.0, 0.3 and 1.2 mg/L at 3, 6 and 12 months. Despite large numerical reductions, statistical significance was not reached, likely due to small sample size and incomplete follow-up (p≈0.19–0.20, n=4 at each time point). Mean eGFR remained stable or improved (75.5 vs 83.8, 80.5 and 95.7 mL/min/1.73 m² at baseline, 3, 6 and 12 months), without statistically significant changes (p=0.30–0.42). All patients experienced a marked clinical reduction in attack frequency within the first 3 months, and systemic glucocorticoids could be tapered or discontinued in all cases. TCZ was generally well tolerated: no serious infections, neutropenia, hepatotoxicity or cardiovascular events were observed during a median treatment duration of 8 months (range 2–24); one patient discontinued due to lack of perceived benefit, and one patient was lost to follow-up.
Conclusions: In this small real-world series of highly refractory tophaceous gout with prior failure of anakinra, subcutaneous tocilizumab was associated with rapid clinical improvement, marked CRP reduction and preserved renal function. Although laboratory changes did not reach statistical significance, these findings support IL-6 blockade as a potential therapeutic option in selected D2T cases, warranting further investigation.