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Recurrent pericarditis, a condition associated with significant morbidity and even increased mortality, has received more recent welcome attention, mainly because of the emergence of promising, new, immune-modulating treatments. Imazio et al 1 conduct a systematic review and meta-analysis of 2 randomised controlled trials (RCT)2 3 and 5 observational studies (OS), examining the efficacy and safety of anti-interleukin-1 (IL-1) agents (all anakinra, bar 1 RCT using rilonacept3 in 397 pooled patients with recurrent pericarditis despite standard medical therapy (non-steroidal anti-inflammatory drugs, colchicine, corticosteroids). While this paper is not without controversy (below we will delve further into the potential for bias due to the small number of studies, small effect size and funnel plot concerns), it nonetheless merits special attention given limited data on this topic and the need for more clinical research.
The authors review hypothesis-generating, mechanistic data for the IL-1 pathway, a much-needed additional therapeutic target for the treatment of recurrent pericarditis. IL-1 is a pro-inflammatory cytokine that mediates the NLR pyrin domain 3 protein (NLRP3) that is part of the inflammasome signalling pathway, which in turn stimulates the synthesis of systemic inflammatory molecules such as cyclo-oxygenase and prostaglandins. Through the use of IL-1 inhibitors, namely anakinra and rilonacept, the authors highlight the IL-1/NPL3 pathway as an important mediator of systemic inflammation in pericarditis. Figure 1 illustrates the pathogenic role of the IL-1 pathway in recurrent pericarditis.4
Patients receiving anti-IL-1 agents had a statistically significant lower incidence rate ratio (IRR) (number of events divided by the person-time at risk) for recurrent pericarditis (IRR 0.06, 95% CI 0.03 to 0.14, I2=95%; p<0.00001) compared with patients receiving placebo and/or standard medical therapy (figure 2)1 This observed efficacy was consistent across the pooled …
Contributors Each author has contributed to this work sufficiently to meet standard criteria for authorship.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; externally peer reviewed.