Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial

Abstract

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.

EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome

“…Limiting glucocorticoid exposure to the lowest effective dose to control active disease for the shortest duration possible and eventually discontinuation, as well as weighting the benefits and risks before starting systemic glucocorticoids, can help reduce cardiovascular harm. Several anti-inflammatory agents (eg, colchicine, 122 anti-IL1b 123 ) have been shown to lower cardiovascular outcomes in randomised controlled trials for secondary prevention of cardiovascular disease in the general population and other trials are ongoing (eg, hydroxychloroquine 124 ) but further evidence is needed on the cardiovascular outcomes and safety of such immunoregulatory agents in RMDs. Although the role of hydroxychloroquine in APS, and of non-steroidal antiinflammatory drugs (NSAIDs) in SLE, was examined in our SLR (Supplementary SLR report, section II), the panel agreed that any statement on the use of these medications should be deferred until more robust evidence is available.…”

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay

“…As mentioned before, the achievement of the therapeutic concentration of HCQ for PVD may need 4–6 weeks or even >90~120 days, depending on the patient’s status [ 11 ]. As such, short-term use of HCQ may be without effect on aHR for PVD [ 49 ].…”

“…The index date was defined as the first prescription date of HCQ after diagnosis of the ILD cohort. Slow onset of anti-inflammatory therapeutic efficacy is typical for HCQ as it may take up to 4 to 6 weeks for the onset, and 3 to 6 months to achieve maximal clinical efficacy [ 11 ]. Thus, we defined the case cohorts (HCQ users) as patients who used HCQ therapy for ≥28 days after the index date.…”

“…The combination of these factors and the administration of HCQ prevented the development of PAH, and vascular remodeling after monocrotaline, and prevented the progression of established PAH in an experimental study [ 10 ]. However, the prolonged use of HCQ has been implicated in the development of conduction disturbances and myocardial dysfunction, leading to heart failure [ 11 ]. Owing to the cross-reaction of the heart and lung, heart failure was predisposed to PAH [ 6 ].…”

Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis

“…The pro-inflammatory cytokine IL-6 was targeted by the specific antibody tocilizumab in the ASSessing the effect of Anti-IL-6 treatment in MI (ASSAIL-MI) trial ( 296 , 297 ), and the treatment attenuated the inflammatory response and the degree of myocardial damage in patients with non-ST-elevation myocardial infarction. Moreover, after acute myocardial infarction hydroxychlorine reduced the levels of IL-6 at least for a period of 32 months suggesting that this anti-inflammatory drug may reduce cardiovascular events after such an event ( 298 ). However, other anti-inflammatory drugs, like the immunosuppressant methotrexate ( 299 ) or the p38 mitogen-activated protein kinase (MAPK) inhibitor Losmapimod ( 300 ) did not show any effects revealing the specificity of the clinically relevant anti-inflammatory pathways.…”