Real world outcomes in patients with acquired thrombotic thrombocytopenic purpura (TTP) treated with caplacizumab Free

Acquired Thrombotic thrombocytopenic purpura (TTP) is characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, renal and neurologic dysfunction caused by autoantibodies to ADAMTS13. ADAMTS13 cleaves the ultra-large von Willebrand factor (VWF) multimer to a smaller-sized multimer. Accumulation of VWF multimers on the endothelium causes platelet aggregation and thrombosis. TTP without treatment has a mortality of about 90%. Standard treatment for TTP is plasma exchange and corticosteroids. Rituximab is given to target antibody producing B-cells. In recent clinical trials, Caplacizumab (a monoclonal antibody that targets A1 section of VWF and prevents platelet adhesion) has been shown to improve TTP related outcomes. We aim to study the real-world use of Caplacizumab in acquired TTP and compare the outcomes in patients who received Caplacizumab versus those who did not.

METHODS Using TriNetX database, we identified patients with acquired TTP who have received plasmapheresis. Group 1 received SOC (plasmapheresis and corticosteroids) and group 2 received SOC with Caplacizumab. Both groups were analyzed by comparing rate of rehospitalization, ICU admission, thrombocytopenia, hemolytic markers, thrombosis and mortality at 1 month, 3 months, 6 months, and 12 months post treatment. Mortality rates were compared using Kaplan-Meier analysis.

RESULTS Among 1781 patients with acquired TTP who met eligibility criteria, 1694 received standard of care treatment named as SOC group while 87 patients received standard of care along with caplacizumab named as CAP group. The mean age at diagnosis in SOC was 48 years and in CAP group it was 48.1 years. Both groups had more females, 59.6% in SOC and in 65.5% in CAP. At baseline mean Hgb in SOC group was 9.3 g/dl and in CAP group was 9.1 g/dl. Mean platelet count in SOC group was 95.1 × 10³/µL and 106 × 10³/µL in CAP group. Mean total bilirubin and indirect bilirubin at baseline were 2.3 mg/dL and 1.5 mg/dL in SOC group, versus 1.5 mg/dL and 1.1 mg/dL in CAP group. Mean LDH in SOC group was 913 U/L and in CAP group was 663 U/L. Mean creatinine in SOC group was 2.7 mg/dL and in CAP group was 3.4 mg/dL. Mean cardiac troponin I was 1.69 ng/ml in SOC group vs 0.968 ng/ml in CAP group.

More patients received rituximab in CAP group 56.3% (n=49) compared to 16.8% (n=285) in SOC group by 6 months. Thrombocytopenia (platelets < 149 × 10³/µL) was higher 65.5% (n=1109) in SOC than 56.3% (n=49) in CAP group at 1 month and 58.6% (n=51) at 3 months with p-value >0.05. The difference in thrombocytopenia became statistically significant in SOC group at 6 months (69.1%, n=1171) and at 12 months (70.1%, n=1188) compared to CAP group at 6 and 12 months (58.6%, n=51), p-value=0.02.

Higher proportion of elevated total bilirubin > 1.3g/dl was seen in SOC group vs CAP group at 1 month (28.2% vs 13.8%), at 3 months (29.5% vs 14.9%) and at 12 months (32.1% vs 17.2%), p=0.0036. No statistically significant difference was seen in other hemolytic markers (Hgb < 10 g/dl, LDH > 280 U/L, indirect bilirubin > 0.8 g/dl, haptoglobin <28 mg/dl) at 1, 3, 6 and 12 months between SOC and CAP groups. More patients had elevated creatinine >1.4mg/dl in SOC group vs CAP group at 1 month (39.7% vs 19.5%) and at 12 months (43.6% vs 20.7%), p-value <0.0001. A similar proportion of patients had thrombosis at 1 month (10.5% vs 11.5%) and at 12 months (18.1 vs 18.4%) between the two groups, p=0.9.

More patients had statistically significant rehospitalization in the SOC group than CAP group at all timepoints of comparison. At 12 months, the risk difference was 12.2% with 50.2% (n=850) in SOC and 37.9% (n=33) in CAP group, p-value 0.02. ICU admissions were 1.2% at 3 months and 1.6% at 12 months in SOC group. Given ICU admissions were <10 in CAP group, the rate could not be compared between the two groups. No significant difference in mortality rate was observed. The survival probability at 12 months was 82.4% in SOC group vs 94.3% in CAP group.

CONCLUSION Use of Caplacizumab for acquired TTP is associated with reduced risk of thrombocytopenia, elevated bilirubin, renal dysfunction, and hospital readmissions at 1 year compared to patients who received SOC treatment only. There is no difference in incidence of thrombus formation, ICU admission and mortality between SOC and Caplacizumab. Factors regarding real world use of caplacizumab should be explored further to improve outcomes.