Sutimlimab Suppressed CAD Response in Heart Surgery Patient
Suppressing the pro-inflammatory complement pathway using sutimlimab, in addition to other measures, can help prevent red blood cell destruction in patients with cold agglutinin disease (CAD) undergoing major surgery, a recent case report suggests
The study, “Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anaemia 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 found on the surface of red blood cells. For people with CAD, these autoantibodies bind and destroy red blood cells at low temperatures, causing anemia (lack of red blood cells) and subsequent fatigue.
These autoantibodies also can trigger the activation of the complement pathway, which promotes inflammation, further resulting in hemolytic anemia — a specific form of anemia caused by red blood cell destruction.
Many patients with CAD are only mildly anemic, but an infection or trauma can further increase complement pathway activation, resulting in increased red blood cell destruction and hemolytic anemia.
Sutimlimab is a selective inhibitor of complement C1, a part of the complement pathway, which blocks a specific portion of the signaling cascade known as the classical complement pathway. It is being investigated as a potential treatment for CAD.
Here, researchers described the case of a man with CAD in whom sutimlimab successfully suppressed complement system activation while he underwent major heart surgery.
The patient was in his late 60s and had a 10-year history of coronary heart disease, a disease in which the blood vessels supplying the heart with oxygen — the coronary arteries — are not functioning efficiently.
Previously he had a heart attack that was treated by having three stents — small tubes used to open blood vessels and improve blood flow — placed in his right coronary artery. A reoccurrence of his symptoms one year later led to another stent being placed in his left anterior descending artery, which provides blood to the front left side of the heart. Two other stents also were placed later in the same artery.
When he was diagnosed with CAD, one year after his most recent heart surgery (third stent placement), he was severely anemic and required regular red blood cell transfusions.
He then enrolled in the Phase 3 Cardinal trial (NCT03347396), a recently completed study that assessed the use of sutimlimab in patients with CAD with a recent history of blood transfusions. Following treatment in this trial, his hemoglobin levels increased 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 no longer needed.
However, nine months later, he developed trouble breathing with demonstrated three-vessel disease — an extreme form of coronary artery disease in which blood vessels supplying the heart with oxygen become damaged or diseased, often due to cholesterol accumulation or inflammation.
Also, due to narrowing of the arteries supplying his heart with blood, doctors deemed 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 bloodstream or chemo-immune therapy to reduce antibody production — were not considered viable options due to time constraints.
Clinicians instead chose to use sutimlimab to block the complement pathway and potentially the associated destruction of red blood cells taking place during and after surgery.
The patient was admitted for surgery and given a 6.5 g dose of sutimlimab based on his weight. He underwent surgery two days later with the operating room kept warm. All fluids were kept at 37 C (98.6 F), normal body temperature.
The patient received two coronary grafts, 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 products were given to prevent the replacement of complement C1, which was being inhibited by sutimlimab.
Blood samples were taken at various time points: at admission; prior to surgery; immediately before and after being placed on a bypass machine; and again 24 hours after surgery.
Overall, hemoglobin levels remained stable throughout surgery, with no signs of red blood cell destruction. The patient was discharged in good condition to a local hospital five days after surgery.
As the clinicians expected, there was an increased inflammatory response that peaked at two days post-surgery. Despite this, however, red blood cell destruction did not increase.
On day 14 after surgery, the patient was fully mobile and showed no signs of hemolysis. A measurement assessing the activity of the complement pathway indicated it remained suppressed up to two weeks following surgery.
Authors suggest that this case demonstrates that even in a surgery entailing significant trauma and associated with a high risk of CAD flare-up, sutimlimab, alongside other measures, suppressed complement system activation.
“Hence, sutimlimab is potentially a new and safe tool for patients with CAD undergoing major surgery,” they wrote.