Comparable effectiveness of intensive intravenous and less intensive immunosuppressive treatment in retroperitoneal fibrosis: a retrospective real-world cohort study.

Retroperitoneal fibrosis (RPF) is a rare fibro-inflammatory disease frequently complicated by ureteral obstruction and renal impairment. Due to its rarity, heterogeneous clinical course, and the absence of standardized treatment guidelines, optimal immunosuppressive management of RPF remains uncertain. This study aimed to evaluate the real-world effectiveness and safety of different immunosuppressive treatment strategies in patients with RPF. A retrospective, single-center observational study was conducted including patients with idiopathic or immune-mediated RPF treated between 2010 and 2025. Patients were grouped according to treatment strategy: intensive intravenous therapy with cyclophosphamide or rituximab, or less intensive oral immunosuppressive therapy including methotrexate, mycophenolate mofetil or azathioprine. Treatment effectiveness was assessed using a composite endpoint incorporating clinical, laboratory and radiological response. Secondary outcomes included renal function, relapse, treatment safety, and glucocorticoid exposure. Twenty-nine patients were included in the analysis, of whom 11 received intensive therapy and 18 were treated with less intensive oral immunosuppressive regimens. Overall treatment effectiveness was achieved in 68% of evaluable patients and did not differ significantly between groups (OR 2.67, 95% CI 0.41-17.17). Clinical, laboratory, and radiological responses did not differ significantly between treatment groups. Hydronephrosis resolved in 75% of affected patients. Median serum creatinine levels improved during follow-up in both treatment groups, without significant intergroup differences at last observation (1.20 mg/dL [1.10-1.30] vs. 1.20 mg/dL [0.80-1.40]). The median relative reduction in periaortic mass thickness was 41.2% (24.45-53.95). No significant differences in overall safety outcomes were observed. In this real-world cohort of patients with RPF, intensive intravenous immunosuppressive regimens were not associated with superior treatment effectiveness compared with less intensive oral therapies. These findings support an individualized approach to treatment selection in RPF, taking disease severity, renal involvement and patient-specific factors into account. Prospective studies in larger cohorts are needed to further define optimal long-term management strategies for this rare disease.