Clinical experience with the interleukin-1β blocker canakinumab in patients with chronic tophaceous gout: abolishment of arthritis and prevention of exacerbations when allopurinol is used

Abstract

The interleukin (IL)-1β inhibitor canakinumab may be effective in relieving an acute gout attack and in preventing an arthritis exacerbation. However, there are insufficient data on the use of this agent to abolish and prevent arthritis in patients who are resistant to another anti-inflammatory therapy. Objective : to evaluate the efficacy of the interleukin (IL)-1β inhibitor canakinumab in patients with chronic tophaceous gout, who are resistant to traditional anti-inflammatory therapy, in order to abolish arthritis and to prevent its exacerbations when adjusting the optimal dose of allopurinol. Subjects and methods. An open-labeled prospective study was conducted in 20 patients (mean age, 54.5±12.7 years) with chronic tophaceous gout. Serum uric acid (UA) levels were 486.3±135.2 μmol/l. The inclusion criteria were crystal-verified gout; arthritis affecting more than 5 joints; inefficacy of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), or colchicine when used for over a month; more than 4 arthritis attacks during year. The exclusion criteria were Stage ≥3 chronic kidney disease, infectious diseases. All the patents received a single subcutaneous injection of canakinumab 150 mg. NSAIDs and/or colchicine was discontinued a day before the injection. The number of swollen and tender joints and visual analogue scale (VAS) pain intensity were estimated before and 14 and 120 days after the injection; SF-36v1 and HAQ changes were assessed before and 120 days after the injection. 14 days after the injection, all the patients were given allopurinol, the dosage of which was individually adjusted, by starting on 100 mg/day and subsequently increasing by 100 mg/day every 2 weeks (not more than 800 mg/day) until the goal UA level (<360 μmol/l) was reached. Results. 14 days after canakinumab injection, arthritis was abolished in 8 (40%) patients and 3 patients needed to continue NSAID therapy. Following 14 days of the injection, there was a decline in the number of swollen joints from 12 [5; 16] to 3 [0; 4] (р<0.001), that of tender joints from 10 [1; 25] to 4 [0; 15], VAS pain from 60 to 24 [10; 30] mm, and high-sensitivity serum C-reactive protein from 29 [1.8; 168] to 7.6 [0.2; 41] mg/l. After 120 days, the decline in the indicators remained in the majority of the patients; there were significant improvements in physical component summary (PCS) from 39±6.9 to 44.5±9.4 (р=0.04), mental component summary (MCS) from 52.6±7.6 to 55.6±8.2 (р=0.01); HAQ scores decreased from 1 [0.1; 1.5] to 0.7 [0; 0.9] (р=0.049). No attacks of arthritis were observed in 10 patients. Seven and 3 patients had 1 and 2 arthritis attacks, respectively. 17 (85%) patients achieved the goal serum UA level; the latter was <300 μmol/l in 12 (60%) patients. Median allopurinol dosage was 400 [300; 600] mg/day. By the completion of the study, 4 (20%) patients required continued NSAID therapy. Conclusion. The use of canakinumab in patients with severe gout, who are resistant to therapy with NSAIDs, colchicine, and GCs, is an effective method to treat arthritis and to prevent acute arthritis attacks during allopurinol therapy. The administration of high-dose allopurinol causes a target reduction in serum UA levels in most patents.