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.
RCT Entities:
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.
Authors: Stephen P Juraschek; J Michael Gaziano; Robert J Glynn; Natalya Gomelskaya; Vadim Y Bubes; Julie E Buring; Robert H Shmerling; Howard D Sesso Journal: Am J Clin Nutr Date: 2022-09-02 Impact factor: 8.472
Authors: João Pedro Ferreira; Silvio E Inzucchi; Michaela Mattheus; Thomas Meinicke; Dominik Steubl; Christoph Wanner; Bernard Zinman Journal: Diabetes Obes Metab Date: 2021-10-04 Impact factor: 6.408
Authors: Mounica Vallurupalli; Jean G MacFadyen; Robert J Glynn; Tom Thuren; Peter Libby; Nancy Berliner; Paul M Ridker Journal: Ann Intern Med Date: 2020-03-24 Impact factor: 25.391
Authors: Yang Yang; Leon J Delalio; Angela K Best; Edgar Macal; Jenna Milstein; Iona Donnelly; Ashley M Miller; Martin McBride; Xiaohong Shu; Michael Koval; Brant E Isakson; Scott R Johnstone Journal: J Immunol Date: 2020-04-20 Impact factor: 5.422
Authors: Nor Amira Syahira Mohd Azmi; Norsham Juliana; Sahar Azmani; Nadia Mohd Effendy; Izuddin Fahmy Abu; Nur Islami Mohd Fahmi Teng; Srijit Das Journal: Int J Environ Res Public Health Date: 2021-01-14 Impact factor: 3.390
Authors: Lisandro D Colantonio; Kenneth G Saag; Jasvinder A Singh; Ligong Chen; Richard J Reynolds; Angelo Gaffo; Timothy B Plante; Jeffrey R Curtis; S Louis Bridges; Emily B Levitan; Ninad S Chaudhary; George Howard; Monika M Safford; Paul Muntner; Marguerite Ryan Irvin Journal: Arthritis Res Ther Date: 2020-04-16 Impact factor: 5.156