Methotrexate plus prednisone in patients with relapsing idiopathic retroperitoneal fibrosis

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease, characterised by a fibroinflammatory tissue surrounding the aortoiliac axis and frequently entrapping the ureters.1 ,2 Glucocorticoids effectively induce remission, but 24% to 72% of patients relapse, half of them repeatedly.3 ,4 Immunosuppressants and glucocorticoids are usually required in relapsing IRF but no studies are available. In this prospective, open-label trial we enrolled 16 relapsing patients with IRF (July 2004 to April 2011) aged 18–85 years and with an estimated glomerular filtration rate (eGFR)>50 ml/min5 after ureteral decompression (if required), and treated them with methotrexate and prednisone for 12 months. Relapse was defined in case of mass enlargement, hydronephrosis, or disease-related symptoms associated with high inflammatory markers.3 Prednisone was given at 0.5–1 mg/kg/day depending on flare severity, tapered to 12.5–10 mg/day by month 3, 7.5–5 mg/day by month 6 and maintained at 5–2.5 mg/day until month 12. Methotrexate was given at 15–20 mg/week until month 12. After month 12, the clinician was free to continue or withdraw the treatment. The primary endpoint was remission (at month 12) defined as a stable, reduced mass and absence of hydronephrosis, disease-related symptoms and normal inflammatory markers.3 Secondary endpoints were changes in erythrocyte sedimentation rate (ESR), C reactive protein (CRP), IRF thickness and eGFR at 6–12 months and last follow-up. Patients who relapsed or stopped treatment for toxicity were considered treatment failures. Differences in eGFR, ESR, CRP and IRF thickness were assessed using the Wilcoxon test, and relapse-free survival by the Kaplan–Meier method with comparisons between patient subgroups analysed via the log-rank test. The trial is registered with Australia New Zealand Clinical Trials Registry (ACTRN12612000845831) and was approved by the local ethics committee. Of the 16 enrolled patients, 10 (63%) were men; the median age was 60 years. Seven patients received an initial prednisone dose of 0.8–1 mg/kg/day while nine received 0.5–0.7 mg/kg/day; the median highest methotrexate dose was 15 mg/week (IQR 14.5–17.5); the median follow-up was 24 months. Six (37%) patients had hydronephrosis and two acute renal failure. During the first year, one patient was lost to follow-up (month 4) and one autonomously stopped treatment (month 6). The remaining 14 were assessable for response at month 12; 11 (79%) were in remission and 3 had treatment failures (due to toxicity in 1 patient and relapse in 2); the median prednisone dose at month 12 was 5 mg/day. Relapse-free survival is shown in figure 1.