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

Schlesinger, Naomi; Alten, Rieke; Bardin, Thomas; Schumacher, H. Ralph; Bloch, Mark; Gimona, A.; Krammer, Gerhard; Murphy, Valda; Richard, Dominik; So, Alexander

doi:10.1136/annrheumdis-2011-200908

Cited by 296 publications

(184 citation statements)

References 39 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Gout is characterized by short‐term periods of clinically apparent inflammation, separated by periods of subclinical inflammation 5, 23. Low‐grade inflammation also has a major role in the development of CVDs, and elevated levels of C‐reactive protein and interleukin‐6 have been found to be associated with increased cardiovascular risk 24.…”

Section: Discussionmentioning

confidence: 99%

Association of Gout With Long‐Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease

Pagidipati

Clare

Keenan

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundEpidemiological studies demonstrating a relationship between gout and cardiovascular disease are older and predate modern cardiovascular preventive therapy. We assessed the contemporary association between gout and cardiovascular disease in patients with obstructive coronary artery disease.Methods and ResultsData were from the Duke Databank for Cardiovascular Diseases, which followed up patients undergoing cardiac catheterization with obstructive coronary artery disease at Duke University Medical Center (1998–2013). We assessed the relationship between gout diagnosis at baseline or during follow‐up and the primary composite outcome of cardiovascular death, myocardial infarction, or stroke, adjusting for differences in baseline clinical factors. Secondary end points included cardiovascular death and all‐cause mortality. New, postbaseline, gout diagnosis was included as a time‐dependent covariate. Among 17 201 patients, 1406 (8.2%) had baseline gout and a high burden of cardiovascular risk factors, but high rates of optimal medical therapy. Over a median follow‐up of 6.4 years, gout diagnosis at time of catheterization was not associated with the primary outcome (hazard ratio [95% confidence interval], 1.05 [0.96–1.15]; P=0.31) or cardiovascular death (hazard ratio [95% confidence interval], 1.10 [0.99–1.22]; P=0.08), but was associated with increased all‐cause mortality (hazard ratio [95% confidence interval], 1.13 [1.05–1.23]; P=0.002). After including new, postbaseline, gout diagnosis, the instantaneous risk of the primary outcome was significantly associated with prior gout diagnosis (hazard ratio [95% confidence interval], 1.15 [1.07–1.25]; P=0.0004).ConclusionsA clinical history of gout is associated with worse outcomes in a contemporary population of patients with obstructive coronary artery disease. This increased risk exists despite high levels of optimal baseline cardiovascular disease medical therapy, suggesting that residual cardiovascular risk is not addressed by standard medical therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of Gout With Long‐Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease

Pagidipati

Clare

Keenan

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…7 In 2013, canakinumab was approved in Europe for preventing remittent gouty arthritis based on its capacity to suppress painful inflammation in acute gout attacks faster than intramuscular steroid injection. 97 Unlike most other drugs used in gout, canakinumab can also be used in patients with CKD. 98 Interestingly, renal function seems to improve when gout is treated with IL-1 inhibition.…”

Section: Il-1-related Drugs and Clinical Datamentioning

confidence: 99%

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

Anders

2016

JASN

210

152

View full text Add to dashboard Cite

Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1b and of the alarmin IL-1a. Dying cells release IL-1a also, independently of the inflammasome. Both IL-1a and IL-1b ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1a/IL-b-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1a/b regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1a/IL-b-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency-approved IL-1-neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1a/IL-b-IL-1R system in kidney disease should be further explored.

show abstract

“…This study showed canakinumab to have a rapid onset in pain relief and increased the time between a flare, likely attributable to its half-life of 21-28 days [29,32]. More adverse events were noted in the canakinumab group, which included infections, neutropenia, and thrombocytopenia [32]. Another study compared canakinumab (single dose versus four divided doses weekly) versus colchicine 0.5 mg daily for gout prophylaxis during initiation of ULT with allopurinol [43].…”

Section: Canakinumab and Rilonaceptmentioning

confidence: 97%

“…One double-blind study assessed the efficacy and safety of one dose of 150 mg canakinumab against one single dose of triamcinolone injection at baseline and during an acute gout attack in patients frequently flaring with contraindications to use of NSAIDs and/or colchicine [32]. This study showed canakinumab to have a rapid onset in pain relief and increased the time between a flare, likely attributable to its half-life of 21-28 days [29,32]. More adverse events were noted in the canakinumab group, which included infections, neutropenia, and thrombocytopenia [32].…”

Section: Canakinumab and Rilonaceptmentioning

confidence: 99%

Current and Emerging Therapies for Gout

Mohammad

Giattino

Keenan

2015

Curr Treat Options in Rheum

View full text Add to dashboard Cite

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

Abstract: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

Cited by 296 publications

References 39 publications

Association of Gout With Long‐Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease

Association of Gout With Long‐Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

Current and Emerging Therapies for Gout

Contact Info

Product

Resources

About