Background Recently there is increasing number of reports pointing out the efficacy of anti-interleukin 1 (anti-IL1) therapy to control AA amyloidosis secondary to autoinflammatory diseases.
Objectives Here we report our experience in IL-1 blockade in patients with AA amyloidosis secondary to Familial Mediterranean fever (FMF)
Methods Eighteen FMF patients with histologically proven secondary AA amyloidosis treated with anti-IL1 agents (canacinumab and anakinra). Creatinine, creatine clearance, 24-hour urine protein, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) parameters were measured before and throughout the treatment period in order to evaluate the response. Patients were closely monitored and adverse events were also reported.
Results Eighteen (8 female, 10 male) patients with AA amyloidosis secondary to FMF who were also on colchicine (mean dose: 1.4±0.7 mg/day) were started on anti-IL1 agents (8 on canakinumab, 13 on anakinra, 3 on both). The mean age was 41.9±11.4 years, while the mean duration of FMF was 21.5±8.9 years. The mean follow-up period on anti-IL1 was 16.5±11.7 months (10.9±7.3 months on anakinra; 18.8±10.7 months on canakinumab).
Ten patients are still on anti-IL-1 therapy (7 on anakinra, 3 on canakinumab). Renal functions remained stable after therapy for 5 out of 10 patients (creatinine from 1.2±0.6 mg/dl to 1.1±0.6 mg/dl; creatine clearance from 82.3±49.5 ml/min to 87.7±53.2 ml/min; 24-hour urine protein from 1094.2±995.4 mg/dl to 885.0±725.0 mg/dl), while CRP (from 15.7±9.5 mg/L to 1.3±0.9 mg/L) and ESR (from 41.8±15.5 mm/h to 15.5±3.7 mm/h) decreased. Renal functions and acute phase reactants improved with therapy (creatinine from 0.7±0.7 mg/dl to 0.7±0.7 mg/dl; creatine clearance from 81.9±79.4 ml/min to 93.3±65.9 ml/min; 24-hour urine protein from 6963.9±7514.0 mg/dl to 304.8±81.5 mg/dl; CRP from 29.6±18.1 mg/L to 28.0±46.8 mg/L; ESR from 63.8±45.7 mm/h to 32.3±44.7 mm/h) for four patients. Renal functions deteriorated after anakinra and it was switched to other biological agents for the remaining patient. However since he progressed to end stage renal disease and started hemodialysis, anakinra was re-introduced to take control over attacks. Global patient assessment score of the whole group decreased significantly (from 8.6±1.6 to 1.2±1.8) with IL-1 blockade.
Anti-IL-1 therapy was discontinued in 8 patients, 3 of them were on anakinra (due to unresponsiveness in 2 and allergic reaction in 1), 5 were on canakinumab (due to increase in proteinuria during the course of treatment in 3, lichen plans in 1 and one was lost to follow up although showed improvement during the follow-up period, then the treatment was terminated since he developed lung adenocarcinoma). Anakinra was switched to canakinumab due to allergic reaction in one and unresponsiveness in two patients
Conclusions Anti-IL1 therapy can improve renal functions and stabilize patients with AA amyloidosis secondary to FMF. The efficacy and safety of anti-IL1 therapy in this group of patients are needed to be verified by further researched.
Disclosure of Interest None declared