Anticytokine Therapy Shows Promise in Acute Gout
So A, De Meulemeester M, Pikhlak A, et al
Arthritis Rheum. 2010;62:3064-3076
Typical therapies for acute flares of gout are the anti-inflammatory therapies nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or corticosteroids (either intra-articular or systemic) as well as pain medications, such as acetaminophen and opiates. However, not all patients with gout can tolerate these therapies. There is growing evidence of the role of numerous cytokines in acute gouty flares, including interleukin (IL)-1, and there is hope that targeting specific cytokines may lead to improved outcomes in gout.
In this randomized controlled, blinded trial, the study authors investigated the efficacy of various doses of canakinumab, a monoclonal antibody that blocks IL-1beta, for the treatment of acute gouty flares compared with a single intramuscular dose of the steroid triamcinolone acetonide (40 mg). The primary endpoint of this study was to determine what dose of canakinumab was equivalent to the triamcinolone dose.
Two hundred patients with acute gout flare (< 5 days) were enrolled in the study (191 completed). These patients were required to have gouty disease thought by their treating physicians to be refractory to NSAIDs and/or colchicine (or contraindication to these agents); study participants were 93% men, with over 50% having decreased renal function (glomerular filtration rate, < 89 mL/min). Additionally, the study participants could not have received NSAIDs or > 0.6 mg of colchicine 24 hours prior to screening. Patients were given either canakinumab at a single dose of 10 mg, 25 mg, 50 mg, 90 mg, or 150 mg or 40 mg of triamcinolone, and pain responses were measured at multiple timepoints over 7 days after medication; 28-29 patients were in each canakinumab dose arm, and 57 patients were in the triamcinolone arm. The study authors found that all doses of canakinumab resulted in lower pain scores at multiple timepoints after drug dosing compared with triamcinolone. More complicated analyses showed that a canakinumab dose of 23 mg had equivalent efficacy to 40 mg of triamcinolone at 48 hours after treatment. Rescue drug use (prednisone or acetaminophen) was higher in those receiving doses of canakinumab < 150 mg day or triamcinolone. C-reactive protein levels showed greater improvement in the canakinumab-treated patients. Adverse event rates were not significantly different between groups. The study authors concluded that the dose of canakinumab 150 mg resulted in improved pain and less rescue drug use when compared with triamcinolone.
Canakinumab for the Treatment of Acute Flares in Difficult-to-Treat Gouty Arthritis: Results of a Multicenter, Phase II, Dose-Ranging Study
So A, De Meulemeester M, Pikhlak A, et al
Arthritis Rheum. 2010;62:3064-3076
Introduction
Typical therapies for acute flares of gout are the anti-inflammatory therapies nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or corticosteroids (either intra-articular or systemic) as well as pain medications, such as acetaminophen and opiates. However, not all patients with gout can tolerate these therapies. There is growing evidence of the role of numerous cytokines in acute gouty flares, including interleukin (IL)-1, and there is hope that targeting specific cytokines may lead to improved outcomes in gout.
Study Summary
In this randomized controlled, blinded trial, the study authors investigated the efficacy of various doses of canakinumab, a monoclonal antibody that blocks IL-1beta, for the treatment of acute gouty flares compared with a single intramuscular dose of the steroid triamcinolone acetonide (40 mg). The primary endpoint of this study was to determine what dose of canakinumab was equivalent to the triamcinolone dose.
Two hundred patients with acute gout flare (< 5 days) were enrolled in the study (191 completed). These patients were required to have gouty disease thought by their treating physicians to be refractory to NSAIDs and/or colchicine (or contraindication to these agents); study participants were 93% men, with over 50% having decreased renal function (glomerular filtration rate, < 89 mL/min). Additionally, the study participants could not have received NSAIDs or > 0.6 mg of colchicine 24 hours prior to screening. Patients were given either canakinumab at a single dose of 10 mg, 25 mg, 50 mg, 90 mg, or 150 mg or 40 mg of triamcinolone, and pain responses were measured at multiple timepoints over 7 days after medication; 28-29 patients were in each canakinumab dose arm, and 57 patients were in the triamcinolone arm. The study authors found that all doses of canakinumab resulted in lower pain scores at multiple timepoints after drug dosing compared with triamcinolone. More complicated analyses showed that a canakinumab dose of 23 mg had equivalent efficacy to 40 mg of triamcinolone at 48 hours after treatment. Rescue drug use (prednisone or acetaminophen) was higher in those receiving doses of canakinumab < 150 mg day or triamcinolone. C-reactive protein levels showed greater improvement in the canakinumab-treated patients. Adverse event rates were not significantly different between groups. The study authors concluded that the dose of canakinumab 150 mg resulted in improved pain and less rescue drug use when compared with triamcinolone.