Patricio Cardoso-Peñafiel [1,2], Maria Fernanda Del Pino-Zambrano [1,2], Marta Novella-Navarro [2,3], Clara Siso-Hernandez 1, Celia Sanchez-Jimenez 1, Carolina Marín-Huertas [1,4], Laura Cebrián-Méndez [1,4], Leticia Lojo-Oliveira [1,4], Ana Pareja-Martinez [1,4], Almudena , Roman-Pascual [1,4], Carmen Olga Sanchez Gonzalez [1,4], Isabel Fuente-Ruiz 5, Teresa Navio-Marco [1,4], Enrique Calvo-Aranda [1,2,4]
Affiliation(s):
1. hospital Universitario Infanta Leonor, Rheumatology, Madrid, Spain
2. Geacser (study Group On Crystal-induced Arthropathies, Spanish Society Of Rheumatology), Madrid, Spain
3. Hospital Universitario La Paz, Rheumatology, Madrid, Spain
4. Universidad Complutense De Madrid, Medicine, Madrid, Spain
5. Universidad Alfonso X, Medicine Student, Madrid, Spain
Background: Treat-to-target strategies are recommended in gout management. However, concerns about safety and tolerability often delay dose escalation of urate-lowering therapy (ULT), limiting achievement of target serum urate (SU) levels in routine practice.
Objectives: To evaluate the effectiveness of a pragmatic allopurinol dose escalation strategy in achieving target SU levels in ULT-naïve gout patients, and to assess treatment tolerability and safety in a real-world setting.
Methods: A retrospective observational study was conducted including patients who fulfilled the 2015 ACR EULAR gout classification criteria and were seen during the study inclusion period (August 2018-October 2025) at a specialized gout clinic. ULT-naïve patients initiating allopurinol were included. Treatment started at 150 mg/day for 4 weeks using 300 mg tablets, followed by escalation to 300 mg/day after assessment of adherence and adverse events (AEs) via nurse-led telephone follow up, with further dose adjustments according to tolerability and achievement of the SU target (<6 mg/dL) over 6 months. Patients with advanced chronic kidney disease (CKD) or prior allopurinol hypersensitivity were excluded. Demographic, clinical and laboratory data were collected at baseline, 1 month and 6 months. Differences between groups were assessed using chi- square, t test or Wilcoxon test as appropriate (<0.05).
Results: Ninety-five patients were included; 95% were male, with a mean age of 62.8± 11 years and mean BMI of 30± 4.5 kg/m2. Subcutaneous tophi were present in 25%. Baseline SU was 8± 1.4 mg/dL and mean estimated glomerular filtration rate (eGFR) was 81.1± 12.9 mL/min/1.73m2; 10.5% had mild-to-moderate CKD. Attack prophylaxis consisted mainly of colchicine (93%), with occasional use of NSAIDs and glucocorticoids. At 6 months, mean SU decreased from 8± 1.4 mg/dL to 5.1± 1.2 mg/dL (<0.01), with 77.9% of patients achieving SU <6 mg/dL and 51.6% SU <5 mg/dL. Patients achieving SU <5 mg/dL were younger (p = 0.02). Those reaching SU <6 mg/dL showed a significant reduction in C-reactive protein (p = 0.004) and a modest improvement in eGFR (+2 mL/min/1.73m2; p = 0.01). Gout attacks occurred in 11.6% during the first month and 17.9% over the 6-month follow-up. Mild AEs (diarrhea or constipation) were reported in 2.1%; transient transaminase elevations occurred in 10.5% at 1 month and 9.5% at 6 months.
Only 8.4% of patients discontinued or switched therapy due to intolerance. No severe cutaneous reactions were observed.
Conclusions: In routine clinical practice, a pragmatic allopurinol escalation strategy using 300 mg tablets was effective and well tolerated in ULT-naïve gout patients. Most patients achieved recommended SU targets at 6 months, with a favorable safety profile, supporting early dose optimization in real world settings.