Anti-inflammatory drugs being evaluated for cardiovascular disease linked to chronic kidney disease

– Despite extensive efforts in recent decades to address the increasing risk of heart disease and mortality in severe chronic kidney disease, including with statins, there have been no breakthrough improvements in treatment. Therefore, these studies are very important. The focus is whether inflammation can be a successful treatment target, says Bengt Fellström, Senior Professor in Renal Medicine at Uppsala University Hospital/Uppsala University, national coordinator and member of the steering committee for one of the studies.

Chronic kidney disease is a serious condition, which means that the body does not get rid of waste products and water in sufficient quantities. Many patients need dialysis. In addition, chronic kidney disease often leads to a greatly increased risk of cardiovascular complications. The risk gradually increases the longer the dialysis treatment lasts. The main risk factors are high blood pressure, diabetes, dyslipidaemia, calcium-phosphate-PTH abnormalities, time on dialysis and systemic inflammation, i.e. inflammation in several organs at the same time.

Several studies in recent years have tested drug candidates that block the effects of interleukin-6, a protein that is an important messenger between immune system cells, showing positive effects on biomarkers related to inflammation and heart disease.

A large international multicentre study has been launched in 6 200 patients with renal impairment, evaluating a monoclonal antibody against interleukin-6.

– This is a targeted drug against the protein interleukin-6, which is used by the immune system to fight certain foreign substances. The aim of the study is to investigate whether the treatment actually reduces the incidence of cardiovascular disease. Patients will be followed for three years, says Maria Eriksson Svensson, Consultant and Professor in Renal Medicine at Uppsala University Hospital/Uppsala University, and principal investigator in Uppsala.

Another international, randomised study will start shortly, which will include around 2,100 dialysis patients. It is a so-called phase III study, which will start in the United States in mid-year and then gradually in Europe and Sweden. Patients will be randomised into two groups, one of which will receive the new drug candidate, the other an IL6 blocker. Patients will be recruited at nearly 200 dialysis clinics, including Uppsala University Hospital. Previously, a phase II study has shown very favourable effects on biomarkers linked to heart disease. The results are published in the prestigious medical journal Nature Medicine.

– We will evaluate an anti-inflammatory drug, a monoclonal antibody/IL6 inhibitor, in patients with chronic kidney disease and high-risk patients on dialysis. Patients will be followed up for four to five years to capture the effect on cardiovascular complications. In addition, we will identify safety aspects as dialysis patients have an increased susceptibility to infection, says Maria Eriksson Svensson.