Background/Purpose: anakinra has been used off-label for the treatment of severe episodes of acute inflammation (EAIs) in gout. Only a retrospective series of 3 patients has reported the use of ankinra as prophylaxis when used in an intermittent schedule. Therefore studies are needed to explore whether a low-dose prescription of anakinra would be effective in patients with severe difficult to treat gout and a formal contraindication of other current treatments for the prophylaxis of AEIs when starting urate-lowering therapy (ULT).

Methods: an agreement between the Rheumatology and Pharmacy Divisions was approved to treat with anakinra patients with severe or recurrent EAIs and a formal contraindication for current treatments for prophylaxis (colchicine and NSAIDs) and requiring repeated doses of parenteral corticosteroids not acceptable from the clinical point of view. As a pilot study, patients with crystal-proved gout were included in a cohort for follow-up from Jul 2011 to Jan 2013. All patients were scheduled for a 6-month period of treatment: anakinra 100 mg sc once a week with additional 100 mg doses on demand during the first 3 months and only on demand 100 mg sc doses from month 3 to 6. In addition to full clinical evaluation, serum urate, hsC-reactive protein, estimated glomerular filtration (CKD_EPI), complete blood cell counts, and liver function tests were tested once a month for the first three months, and at 6-month follow-up. AEIs were evaluated using the EULAR/ACR preliminary criteria for self-referred AEIs in gout and expressed as EAIS/patient-year exposure.

Results: 11 patients with chronic tophaceous (either subcutaneous or ultrasonographic/MRI), polyarticular (> 3 joints involved), crystal-proven gout were been included in the protocol. Ten were 10 men, mean age was 60±14 years (median 61, IQ range 48-69), time from the onset of gout 8±5 years (8, 5-15), subcutaneous tophi in 9/11, chronic heart failure 4/11, CKD 3-5 in 8/11, serious AEs to NSAIDs in 9/11. Diabetes or steroid-induced hyperglycemia in 8/11. Febuxostat 80 to 120 mg/day was prescribed to 6 patients, allopurinol 50 up to 300 mg/day to 6 patients (average dose 5.2 mg/ml FG-day). One patient was on hemodialysis and one showed normal serum urate and no need for urate-lowering agents.

Results are shown in Table. In the 0-3 period, 4/11 required additional doses, and 6/11 while on demand dosing from month 3-6. A patient had an episode of heart failure (4^th in the year) but was maintained on treatment, doing well 16 months after treatment. No intercurrent infection was observed in any patient. No local reaction complaint was retrieved with a weekly schedule.

Conclusion: this pilot study is, to our knowledge, the first to prospectively explore in pre-established doses the efficacy of low-dose anakinra for the prophylaxis of AEIs in patients with severe comorbidities and difficult to treat tophaceous gout.  These encouraging results deserve further studies.