By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved canakinumab, an interleukin-1 beta-blocker, to treat gout flares. This drug was approved in 2009 for treating children and adults with cryopyrin-associated periodic syndromes (CAPS), a serious, life-long, auto-inflammatory disease. It was approved subsequently for active systemic juvenile idiopathic arthritis, three rare periodic fever syndromes, and active Still’s disease. Canakinumab is a recombinant humanized anti-interleukin-1 beta monoclonal antibody that targets interleukin-1 beta. It is distributed as Ilaris.
INDICATIONS
Canakinumab can be prescribed to adults in whom nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.1
DOSAGE
Administer 150 mg subcutaneously.1 If retreatment is required, wait at least 12 weeks before administering the next dose. Canakinumab is available as a single-dose vials containing 150 mg/mL.
POTENTIAL ADVANTAGES
Canakinumab is more effective than intramuscular triamcinolone acetonide (40 mg) in pain intensity and time to new flares in patients unable to use NSAID and/or colchicine.1
POTENTIAL DISADVANTAGES
Canakinumab may interfere with immune response to infection; therefore, the risk of serious infection may be higher.1 In clinical trials, researchers observed transient cytopenia. These include leukopenia (≤ 0.8 × lower limit of normal [LLN]; 6.4% vs. 1.4% for triamcinolone acetonide), neutropenia (absolute neutrophil count < 0.9 × LLN; 15.9% vs. 2.1%), and thrombocytopenia (platelet counts < 0.9 LLN; 16.3% vs. 12.5%).1 Hypertriglyceridemia event rates were higher with canakinumab (5.6% vs. 1.9%). Other adverse reactions include infections (e.g., nasopharyngitis, upper respiratory tract infections, urinary tract infections).1 Avoid administering a live virus vaccine concurrent with canakinumab.
COMMENTS
Activation of resident macrophages and infiltrating neutrophils, along with concomitant overproduction of interleukin-1 beta, is triggered by deposition of uric acid crystals.1 The efficacy of canakinumab to treat gout flares was demonstrated in two 12-week, randomized, double-blind, active-controlled studies and a third study using a prefilled syringe.1,2 Study participants reported at least three gout flares in the previous year. NSAIDs and/or colchicine were contraindicated, not tolerated, or ineffective. Seventy-three percent of participants reported three to six flares in the prior year, and 27% reported seven flares or fewer.
Participants were randomized in the three studies to canakinumab (n = 682) or triamcinolone acetonide (40 mg intramuscularly; n = 490) at baseline and thereafter treated upon a new flare. Co-primary efficacy endpoints were the patients’ assessment of gout pain intensity at the most affected joint at 72 hours post-injection (0-100 visual analog scale) and time to first new flare.
Overall, canakinumab provided significantly better pain relief and reduced the risk of new flares vs. intramuscular triamcinolone acetonide. In a pooled analysis of participants unable to use NSAIDs and/or colchicine, canakinumab resulted in a mean pain score of 25 mm vs. 35.7 mm (P < 0.01) at 72 hours (mean baseline of 74.1 mm) and 56% reduction in new flares over 24 weeks.2 The mean number of per patient new flares was significantly lower with canakinumab (0.4 vs. 0.87). Canakinumab produced a rapid decrease in high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A levels.1,2
CLINICAL IMPLICATIONS
Gouty arthritis is the most common inflammatory arthritis in men. It results from elevated body uric acid pools. Urate-lowering therapy is recommended for patients with infrequent flares (two or fewer per year).3 For frequent flares, the American College of Rheumatology recommends low-dose colchicine, NSAIDs, or glucocorticoids as appropriate first-line therapy.3 An interleukin-1 inhibitor is conditionally recommended, over no therapy, for those in whom first-line anti-inflammatory therapies are ineffective, poorly tolerated, or contraindicated. Canakinumab does not appear to adversely affect patients with cardiovascular (CV) risk. A 150-mg dose administered every three months in subjects with previous myocardial infarction and elevated hs-CRP has been shown to reduce the risk of recurrent CV events vs. placebo.4
In 2011, the manufacturer asked the FDA to approve canakinumab to treat gout. However, an advisory panel turned down the request.5 The FDA required additional studies and a more defined target population to result in the current approval. The current cost for 150 mg of canakinumab is $17,816 per dose.
REFERENCES
1. Novartis. Ilaris prescribing information. August 2023.
2. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: Results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012;71:1839-1848.
3. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken) 2020;72:744-760.
4. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377:1119-1131.
5. Drugs.com. Ilaris FDA approval history.
Canakinumab can be prescribed to adults with gout in whom nonsteroidal anti-inflammatory drugs and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.
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