Caplacizumab improves outcomes in aTTP

The incidence of aTTP-related death was 0% (n=0) in the caplacizumab arm and 4.1% (n=3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n=3) and 38.4% (n=28), respectively. And the incidence of at least 1 major thromboembolic event was 8.5% (n=6) and 8.2% (n=6), respectively.

The researchers also assessed aTTP recurrence during the overall study period, which occurred in 12.7% (n=9) of patients in the caplacizumab arm and 38.4% (n=28) in the placebo arm (P<0.001).

During the follow-up period, there were 6 relapses (9.1%) in the caplacizumab arm but none in the placebo arm.

“This tells us something about the pathophysiology of TTP and the role of caplacizumab,” Dr Scully said. “All of these patients, on stopping caplacizumab, had ADAMTS13 levels less than 5%. Therefore, it was important that their treatment was continued to ensure removal of antibody.”

According to the International TTP Working Group consensus definition, none of the patients in the caplacizumab arm and 7.0% (n=5) of patients in the placebo arm had refractory aTTP (P=0.018).

The mean number of days of plasma exchange during the overall treatment period was 5.8 days in the caplacizumab arm and 9.4 days in the placebo arm (a 38% relative reduction). The mean volume of plasma used was 21.3L and 35.9L, respectively (a 41% relative reduction).

The mean duration of hospital stay was 9.9 days in the caplacizumab arm and 14.4 days in the placebo arm (a 31% relative reduction).

For patients admitted to the ICU (28 in the caplacizumab arm and 27 in the placebo arm), the mean number of days in the ICU was 3.4 days in the caplacizumab arm and 9.7 days in the placebo arm (a 65% relative reduction).

Safety

“The safety profile [of caplacizumab] was comparable to previous results and in keeping with the mechanism of action,” Dr Scully said.

The proportion of patients with at least 1 treatment-emergent AE was 97.2% in the caplacizumab arm and 97.3% in the placebo arm.

The proportion of patients with at least 1 study-drug-related AE was 57.7% in the caplacizumab arm and 43.8% in the placebo arm. The rate of discontinuation due to at least 1 AE was 7.0% and 12.3%, respectively.

The incidence of bleeding-related AEs was higher in the caplacizumab arm (45.6%) than the placebo arm (23.3%).

Bleeding-related AEs (in the caplacizumab and placebo arms, respectively) included epistaxis (23.9% and 1.4%), gingival bleeding (11.3% and 0%), bruising (7.0% and 4.1%), hematuria (5.6% and 1.4%), vaginal hemorrhage (4.2% and 1.4%), menorrhagia (2.8% and 1.4%), catheter site hemorrhage (2.8% and 4.1%), injection site bruising (2.8% and 2.7%), hematochezia (2.8% and 0%), and hematoma (2.8% and 0%).

The proportion of patients with at least 1 serious AE was 39.4% (n=28) in the caplacizumab arm and 53.4% (n=39) in the placebo arm. The proportion of patients with at least 1 study-drug-related serious AE was 14.1% (n=10) and 5.5% (n=4), respectively.

During the treatment period, there were no deaths in the caplacizumab arm and 3 deaths in the placebo arm. There was 1 death in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.