Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: Although studies have shown that interleukin-1β (IL-1β) inhibitors can shorten gout attacks, whether they can prevent gout attacks is unclear.
Objective: To examine the relationship among canakinumab, a monoclonal antibody targeting IL-1β; serum uric acid levels; and the incidence of gout attacks.
Design: Secondary exploratory analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01327846).
Setting: Many clinical sites in 39 countries.
Participants: 10 059 patients with a prior myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) level of at least 19.1 nmol/L.
Intervention: Random allocation to canakinumab (50 mg, 150 mg, or 300 mg) versus placebo, administered subcutaneously every 3 months.
Measurements: Rates of gout attacks were compared across patients with different baseline concentrations of serum uric acid (≤404.5 µmol/L, 404.6 to 535.3 µmol/L, and ≥535.4 µmol/L) and in different intervention groups in Cox proportional hazards regression models.
Results: The median baseline concentration of serum uric acid was 362.9 µmol/L (interquartile range, 309.3 to 428.3 µmol/L), and median follow-up was 3.7 years. Among participants receiving placebo, incidence rates of gout attacks for serum uric acid concentrations of 404.5 µmol/L or lower, 404.6 to 535.3 µmol/L, and 535.4 µmol/L or higher were 0.28, 1.36, and 5.94, respectively, per 100 person-years. Canakinumab did not affect serum uric acid levels over time yet significantly reduced rates of gout attacks at all baseline concentrations of serum uric acid: Hazard ratios were 0.40 (95% CI, 0.22 to 0.73) for concentrations of 404.5 µmol/L or lower, 0.48 (CI, 0.31 to 0.74) for those between 404.6 and 535.3 µmol/L, and 0.45 (CI, 0.28 to 0.72) for those of 535.4 µmol/L or higher.
Limitation: No adjudication of gout attacks.
Conclusion: Quarterly canakinumab administration was associated with significantly reduced risk for gout attacks without any change in serum uric acid levels. These data have relevance for the development of agents for gout that target the IL-1β pathway of innate immunity.
Primary Funding Source: Novartis.
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Source |
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http://dx.doi.org/10.7326/M18-1167 | DOI Listing |
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