2043: Renal Outcomes of Long-term Canakinumab in Patients with Adult Familial Mediterranean Fever (FMF) and Biopsy-Confirmed AA Amyloidosis

Background/Purpose: Canakinumab, an interleukin-1β inhibitor, has demonstrated efficacy in treating colchicine-resistant/intolerant familial Mediterranean fever (FMF). This study aims to assess the efficacy and safety of long-term canakinumab treatment in AA amyloidosis patients with FMF managed at a tertiary center.

Methods: Adult patients diagnosed with FMF based on the Tel Hashomer criteria and treated with canakinumab, followed at the Rheumatology and Nephrology Clinics of Hacettepe University, were retrospectively evaluated. Biopsy-confirmed AA amyloidosis was identified in 25 of the 107 patients who received canakinumab. One patient who did not come for follow-up after canakinumab was excluded from the study. Data on demographics, age at diagnosis, estimated glomerular filtration rate (eGFR) (≥60 vs < 60 mL/min/1.73 m²) and proteinuria levels (urine protein/creatinine ratio, mg/g) before and after canakinumab, use of ACE inhibitors or ARBs, presence of diabetes mellitus, history and timing of renal transplantation, colchicine dose at the last visit, canakinumab dose and interval, treatment duration were recorded.

Results: In total 24 patients (15 F, 9 M) were included for final analysis (Table 1). The median age at diagnosis was 19 (14.5-37.5) years, while the median age of the cohort was 46.5 (39.5-56) years. Of eight patients with renal transplantation, only one underwent transplantation after initiation of canakinumab. At the last visit, the median colchicine dose was 1.0 mg/day (0.5–1.25). During a median duration of 69 months (30.5–88.5), canakinumab was administered at 150 mg/4 weeks in 21 patients, every 8 weeks in one patient, and every 12 weeks in another. In one patient, the dose was escalated to 300 mg/4 weeks. The proteinuria level significantly decreased following canakinumab initiation, from 2423.2 mg/g (454.4–4389) to 724.2 mg/g (188.9–1975.4) at the final visit (p=0.034). Nephrotic-range proteinuria ( >3.5 g/day) was present in 8 patients before treatment, but persisted in only two patients at the final assessment. A change in eGFR category was observed in only five patients (patients 6, 8, 14, 17, and 18)(Figure 1).

Conclusion: Canakinumab therapy, administered for approximately six years, was well tolerated in patients with FMF and biopsy-proven AA amyloidosis, also patients with renal transplantation. High adherence of colchicine and canakinumab treatment was associated with a significant reduction in proteinuria and stabilization of renal function in the majority of patients.