Celacade

Abstract: Chronic heart failure (CHF) remains a leading cause of mortality and morbidity, despite the use of optimal standard-of-care medical therapies. Although the role of the immune system in the pathogenesis and progression of CHF has been well-appreciated, attempts to modify specific systemic immune mediators have been unsuccessful. Building on the modest successes of more broad-spectrum immune therapies, Celacade therapy was developed, a device that induces apoptosis in an ex vivo blood sample. Upon reinjection into the body, the treated blood sample has been shown to have an anti-inflammatory effect. Celacade has been successful in several animal models of disease where inflammation plays an important pathogenic role. Two phase III clinical trials of Celacade have been undertaken. A trial on the use of Celacade in peripheral arterial disease with intermittent claudication was terminated early due to a lack of clinical effect, and a larger trial of Celacade treatment in CHF (ACCLAIM) was completed in 2006. ACCLAIM did not reach the primary end point for the overall study population; however, the study results demonstrated a reduced risk of death or first cardiovascular hospitalization by 39% in patients with New York Heart Association class II CHF and a 26% reduction in patients with class II, III, and IV disease who had no prior history of myocardial infarction. Celacade has been approved for treatment of CHF in these groups of patients in the European Union, and an FDA-mandated confirmatory study of Celacade for possible approval in the United States is in progress.

Abstract: While immunomodulation plays an important role in the therapy of diseases of the rheumatic field, their application is continuously extended to other inflammation-related diseases. The evaluation of cardiac side effects of the numerous immune-modulating substances on the market is complex, since most studies include patients suffering from rheumatic diseases that are known to have an influence on cardiovascular risk factors and tend to be linked with an increased cardiovascular mortality rate. The IgE-neutralizing antibody omalizumab and the pyrimidine synthesis inhibitor leflunomide are potentially associated with increased cardiovascular risk. At the same time healthcare professionals are asked to use special precaution when treating heart failure patients with certain types of anti-TNF-α antibodies and CD20 antibodies, which were reported to be associated with the development of arrhythmias. Other substances are thought to be beneficial to the treatment of cardiovascular diseases. Thus IL-1β blockers were found to be of potential use in the treatment of heart failure. The IL-6 receptor blocker tocilizumab and the anti-p40 antibody ustekinumab have shown partly contradictory results and are still under current investigation regarding their potential beneficial effects on cardiovascular diseases. Intravenous gammaglobulin products and the cytokine profile-modulating therapy celacade have a more comprehensive influence on inflammation and have significant potential in the cardiovascular field. Finally, substances that are naturally produced in the body, such as vitamin D, alpha-1 antitrypsin, estrogen, or progesterone are currently gaining more attention regarding their potential use in the prevention of cardiovascular diseases.