Suppressing the pro-inflammatory complement pathway using sutimlimab, in addition to other measures, may help prevent red blood cell destruction in patients with cold agglutinin disease (CDD) undergoing surgery major, suggests a recent case report
The study, “Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery, ”Was published in the American Journal of Hematology.
Cold agglutinins are autoantibodies directed against proteins present on the surface of red blood cells. For people with coronary artery disease, these autoantibodies bind to and destroy red blood cells at low temperature, causing anemia (lack of red blood cells) and subsequent fatigue.
These autoantibodies can also trigger activation of the complement pathway, which promotes inflammation, further resulting in hemolytic anemia – a specific form of anemia caused by the destruction of red blood cells.
Many patients with coronary artery disease are only mildly anemic, but infection or trauma can further increase complement pathway activation, leading to increased destruction of red blood cells and hemolytic anemia.
Sutimlimab is a selective inhibitor of C1 complement, part of the complement pathway, which blocks a specific part of the signaling cascade known as the classical complement pathway. It is being investigated as a potential treatment for coronary artery disease.
Here, the researchers described the case of a man with coronary artery disease in whom sutimlimab was able to suppress activation of the complement system while undergoing major heart surgery.
The patient was in his late sixties and had a 10-year history of coronary artery disease, a disease in which the blood vessels supplying the heart with oxygen – the coronary arteries – do not work efficiently.
Previously, he had had a heart attack which was treated by placing three stents – small tubes used to open blood vessels and improve blood flow – into his right coronary artery. A recurrence of her symptoms a year later led to the placement of another stent in her left anterior descending artery, which supplies blood to the left front side of the heart. Two more stents were also placed later in the same artery.
When he was diagnosed with coronary artery disease, a year after his last heart operation (third stenting), he was severely anemic and needed regular red blood cell transfusions.
He then enrolled in the Phase 3 Cardinal trial (NCT03347396), a recently completed study that evaluated the use of sutimlimab in patients with coronary artery disease with a recent history of blood transfusions. After treatment in this trial, his hemoglobin level dropped from 10 grams per deciliter (g / dL), a level requiring regular red blood cell transfusions, to 12.0 g / dL, a level at which transfusions are not no longer needed.
However, nine months later, he developed difficulty breathing with demonstrated tri-vessel disease – an extreme form of coronary artery disease in which the blood vessels supplying the heart with oxygen are damaged or diseased, often due to a build-up of blood. cholesterol or inflammation.
Additionally, due to the narrowing of the arteries supplying his heart with blood, doctors felt that the patient needed open-heart surgery immediately. Due to this urgent need for surgery, standard CAD treatments – plasma exchange to remove antibodies circulating in the blood or chemoimmune therapy to reduce antibody production – were not considered viable options due to the constraints. of time.
Instead, clinicians chose to use sutimlimab to block the complement pathway and potentially the associated destruction of red blood cells that occurs during and after surgery.
The patient was admitted for surgery and received a dose of 6.5 g of sutimlimab based on his weight. He underwent surgery two days later with the operating room kept warm. All fluids were maintained at 37 C (98.6 F), normal body temperature.
The patient has received two coronary transplants, in which a blood vessel from another part of the body is used to replace the blocked vessel supplying the heart with blood.
No plasma product was administered to prevent replacement of complement C1, which was inhibited by sutimlimab.
Blood samples were taken at different times: on admission; before surgery; immediately before and after being placed on a bypass machine; and another 24 hours after surgery.
Overall, hemoglobin levels remained stable throughout the surgery, with no signs of red blood cell destruction. The patient was discharged to a local hospital in good condition five days after surgery.
As clinicians expected, there was an increased inflammatory response which peaked two days after surgery. Despite this, however, the destruction of red blood cells did not increase.
By day 14 after surgery, the patient was fully mobile and showed no signs of hemolysis. A measure evaluating the activity of the complement pathway indicated that it remained suppressed for up to two weeks after surgery.
The authors suggest that this case demonstrates that even in surgery involving significant trauma and associated with a high risk of coronary artery disease flare-up, sutimlimab, along with other measures, suppressed complement system activation.
“Therefore, sutimlimab is potentially a safe new tool for patients with coronary artery disease undergoing major surgery,” they wrote.