Background It is usually very problematic to initiate urate-lowering therapy in patients with chronic tophaseous gout resistant to NSAIDs and colchicine therapy[1]. In such cases canakinumab can be used, but its application in practice is not well described.

Objectives To assess efficacy of IL-1β inhibitor canakinumab which concomitant titration of allopurinol to reach the optimal dose to prevent recurrent gouty attacks in patients with severe tophaceous gout, resistant to conventional anti-inflammatory therapy.

Methods Open-label prospective study of 20 pts with tophaceous gout, mean age – 54,5±12,7 y was performed. Mean serum uric acid (UA) level was – 496.3±135.2 μmol/l, serum hs-CRP level – 29 [1.8; 168] mg/l. Inclusion criteria: crystal-proven tophaceous gout, ≥5 joints involved, resistance to conventional therapy with NSAIDs and colchicine (continuous intake for >1 month). All patients received one dose of canakinumab 150 mg subcutaneously. One day prior to canakinumab injection all patients discontinued the intake of NSAIDs or/and colchicine. Tender (TJC) and swollen (SJC) joint counts, pain intensity by VAS scale were routinely assessed before canakinumab injection, and thereafter in 14 and 120 days after injection; SF-36v1 and HAQ scores were calculated before and in 120 days after injection. In 14 days after injection all patients were administered allopurinol. The dose was individually titrated starting from 100 mg/day with biweekly 100 mg gradual increment (to a maximum 800 mg/day) unless target UA level (<360 μmol/l) were achieved.

Results In 14 days after canakinumab injection we observed the completely reduced of gouty arthritis in 8 (40%) of patients, only 3 patients required additional NSAIDs intake. SJC decreased from 12 [6; 16] to 3 [0; 4] in 14 days (p<0.001) and to 1 [0; 6] in 120 days (p<0.001). TJC, pain intensity, serum level of hsCRP also significantly decreased by 14 and 120 days. Improvement in patients' physical and mental condition were also documented. No serious adverse events after injection were observed. 10 (50%) patients never experienced acute gouty arthritis flares during follow up. One acute gouty arthritis flares was documented in 7 patients, and two flares – in 3 patients. Titration of allopurinol dose empowered to achieve target serum UA level in 17 (85%) patients. Median optimal allopurinol dose was 400 [300; 600] mg/day. In 12 (60%) patients serum UA level was <300 μmol/l. Additional NSAIDs required 4 (20%) patients by the end of the study. These patients required the second canakinumab injection.

Conclusions In patients with severe gout resistant to NSAIDs and colchicines canakinumab seems to be effective in therapy chronic gouty arthritis and prevention of acute gouty arthritis flares given urate-lowering therapy is provided. Administration of high allopurinol doses in these patients resulted in achieving target serum UA levels in the majority of patients.

References

1. Schlesinger N. Treatment of chronic gouty arthritis: it is not just about uratelowering therapy. Semin Arthritis Rheum. 2012, 42(2):155–165.

Disclosure of Interest None declared