FRI0479 Efficacy of Colchicine and IL-1 Inhibitors in Amyloidosis Associated with Familial Mediterranean Fever: A Retrospective Analysis

Abstract

BackgroundFamilial Mediterranean fever (FMF), the most common form of hereditary autoinflammatory diseases, is associated with increased risk for secondary (AA) amyloidosisObjectivesWe herein aimed to investigate the features of FMF patients with amyloidosis with respect to their responses to current therapiesMethodsWe enrolled FMF patients with amyloidosis who were regularly followed-up for at least 6 months between 1978 and 2015 into the study. Starting times for colchicine, anakinra or canakinumab and treatment responses were noted. Proteinuria (spot urine protein/creatinine ratio) and C-reactive protein (CRP) levels were measured in every three months of follow-up. Partial response was defined as ≥50% decrease in baseline proteinuria accompanied by a normal serum creatinine level, whereas complete response was defined as <0.3 gr/d baseline proteinuria and stable serum creatinine. Correlations between treatment responders and continuously elevated or normalized CRP levels were tested by using a chi-square testResultsWe identified 79 FMF patients with documented secondary amyloidosis, and all were on colchicine treatment. Their demographic features are shown in Table 1. Mean time to diagnosis after the first symptom was 10 years. Patients were evaluated for partial and complete response after mean follow-up period of 66±85 months. Response to colchicine was observed in 30/65 patients [partial response in 19 (29%), complete response in 11 (17%)]; and 54% was non-responder to colchicine. Anakinra was added to treatment in 22 patients with inadequate response to colchicine, which resulted in partial response in 12, and complete response in 2. Eight patients with partial response to colchicine also received anakinra for better control of attacks and/or elevated acute phase response, and a complete response was achieved in 3 patients. In 3 patients, anakinra was switched to canakinumab because of local injection site reaction (1 patient) and persistence of proteinuria (2 patients). Among those, two patients had partial response, and another underwent hemodialysis due to progressive kidney failure. No significant association was observed between normalized CRP levels and response to treatment with respect to proteinuria and creatinine levels (colchicine; p=0.67, anakinra/canakinumab;p=0.82). No serious infection requiring hospitalization was detected in association with IL-1 blockade.Table 1.Demographic features of FMF patients with amyloidosisMale/Female40/39Age of onset (mean ± SD, range)16±12 (2–68)Age of diagnosis (mean ± SD, range)27±13 (7–70)Family history of FMF47%Disease follow-up duration (mo)66±85 (6–480)Time to diagnosis (mo)121±136 (2–576)Family history of amyloidosis (%)18%Arthritis at presentation (%)60%MEFV variations (n=46)M694V, 68%V726A, 10%M680I, 15%Others, 7%IL-1 inhibitors n (%)43 (54%)Patients on hemodialysis7 (9%)Renal Transplantation n (%)17 (21%)High CRP levels in attack-free periods n (%)31 (39%)ConclusionsAmyloidosis still remains as an important complication of FMF, and a satisfactory respo...

Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

“…Anakinra, a new recombinant homologue of IL-1 receptor antagonist (IL-1Ra) demonstrated its efficacy in colchicine-resistant FMF patients both in randomized clinical trials and observational studies. In long-term follow-up trials, the complete remission was achieved in 12–100% of subjects [ 61 , 62 , 63 , 64 , 65 ] . Patients with FMF-related amyloidosis experienced the improvement or stabilization of renal function and proteinuria after the administration of anakinra [ 61 , 66 , 67 , 68 , 69 ].…”

“…In long-term follow-up trials, the complete remission was achieved in 12–100% of subjects [ 61 , 62 , 63 , 64 , 65 ] . Patients with FMF-related amyloidosis experienced the improvement or stabilization of renal function and proteinuria after the administration of anakinra [ 61 , 66 , 67 , 68 , 69 ].…”

“…Canakinumab, a human monoclonal anti-IL-1β antibody, has been adopted in small cohorts of patients [ 68 , 70 , 71 ]. A randomized trial including patients affected by colchicine-resistant FMF demonstrated a complete response in 61% of the treatment group vs. 6% of placebo group at 16 weeks ( p < 0.001), with 46% of patients maintaining remission with canakinumab longer interval dose of 8 weeks [ 72 ].…”