Table 2.
Cytokine-Targeting Drugs Currently Under Preclinical Investigations or Clinical Trials
| First Author, Year (Ref. #) | Trial | Drug, n (Mechanism) | Dose (mg) | Control, n | Efficacy Endpoints | Outcome (Drug vs Control) |
|---|---|---|---|---|---|---|
| Ridker et al, 2017 (50) | CANTOS | Canakinumab, 6,717 (IL-1β antagonist) | 50, 150, 300 | Placebo, 3,344 | Nonfatal MI, stroke, or cardiovascular death at 48 mo | 4.11% (50 mg) 3.86% (100 mg) 3.9% (300 mg), vs 4.5% (placebo) |
| Ikonomidis et al, 2008 (51) | Anakinra ADHF | Anakinra, 23 (IL-1R antagonist) | 150 | Prednisolone, 19 | Nitrooxidative stress and vascular function at 30-d follow-up | Nitrotyrosine (-38% vs -11%) Flow-mediated dilation (45% vs -9%) Coronary flow reserve (29% vs 4%) Aortic distensibility (45% vs 2%) |
| Giles et al, 2019 (52) | ENTRACTE | Tocilizumab, 1,538 (IL-6 antagonist) | 8/kg | Etancercept, 1,542 | Comparison of time to first occurrence of MACE over 3.2 y | Decrease in MACE, hazard ratio 1.05 (95% CI: 0.77-1.43) |
| Klein et al, 2020 (53) | RHAPSODY | Rilonacept, (IL-6 antagonist) | 320 | Placebo, 160 | Time to pericarditis reoccurrence at 24 weeks | Enrolling |
| Chung et al, 2003 (54) | ATTACH | Infliximab, 101 (TNF-α antagonist) | 5/kg 10/kg |
Placebo, 49 | Circulating inflammatory biomarkers and risk of death at 28 weeks | Elevated mortality risk and/or hospitalization, hazard ratio 2.84 (95% CI: 1.01-7.97) |
| Bissonnette et al, 2012 (55) | NCT00940862 | Adalimumab, 20 (TNF-α antagonist) | 80 | Placebo, 10 | Change in carotid and ascending aorta inflammation by PET scan at 15 weeks | Improvement in target-to-background ratio in both aortic and ascending aorta (-0.26 ± 0.11 and -0.32 ± 0.15) |
Anakinra ADHF = Interleukin-1 Blockade in Acute Heart Failure; ATTACH = Anti-TNF Therapy Against Congestive Heart Failure; CANTOS = Canakinumab Anti-Inflammatory Thrombosis Outcome Study; CI = confidence interval; ENTRACTE = Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors; IL = interleukin; MACE = major adverse cardiovascular event; MI = myocardial infarction; PET = positron emission tomography; RHAPSODY = Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: a Pivotal Symptomatology and Outcomes Study; TNF-α = tumor necrosis factor α.