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aTTP - also referred to as iTTP - is a rare, life-threatening medical emergency4-8

What is aTTP/iTTP?

aTTP, sometimes also referred to as TTP and iTTP, is a rare, life-threatening, thrombotic microangiopathy manifested by microvascular thrombi and consequent thrombocytopenia, hemolytic anemia, and organ ischemia.4-8

Types of TTP8

  • Acquired TTP (also known as immune-mediated thrombotic thrombocytopenic purpura [iTTP])
    • The most common form of TTP; accounts for 95% of TTP cases
    • Caused by autoantibody inhibition of ADAMTS13 activity
  • Hereditary TTP (also known as congenital TTP, inherited TTP, familial TTP, or Upshaw–Schulman syndrome)
    • Rare form of TTP
    • Caused by mutations in the ADAMTS13 gene

~95% of TTP cases are aTTP/iTTP8

Each aTTP/iTTP episode can be unpredictable with microthrombi-driven risks9-11

The pathophysiology of aTTP/iTTP poses a triple threat; PEX and immunosuppressive therapy directly address only 2 of the 3 aspects of the disease2,5,8,12-15

Understanding-Risk-of-aTTP
Understanding-Risk-of-aTTP
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Patient risk remains in aTTP/iTTP despite current treatment with PEX and immunosuppressive therapy6

Mortality remains high

8% to 20% of patients died despite receiving PEX and immunosuppressive therapy, according to a range of studies.*4-6,16

*Literature review of studies with more than 100 patients with TTP.

Thromboembolic events caused by ischemia are common

Nearly 35% of in-hospital TTP deaths (613) were related to ischemia, including MI and stroke, despite receiving PEX.†6

Retrospective claims analysis of hospitalizations with TTP (N=8203).

Relapse threatens patients

Up to 50% of patients had ≥1 recurrence within 30 days of stopping PEX.‡4

Retrospective review of French Reference Centre for TMA registry (N=388).

Increased risk of stroke through clinical remission§

Stroke after recovery with PEX occurred in 0% (0/22) of patients with mean normal ADAMTS13 activity (>70%) and in 27.6% (8/29) of
patients with ADAMTS13 activity ≤70% (P=0.007).||17

||Cohort study of 170 patients with aTTP from 1995 to 2018.

aTTP poses dangerous risks

FIND OUT ABOUT DIFFERENTIATING aTTP

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LEARN ABOUT CABLIVI

§Defined as sustained clinical response either with no PEX and no anti-vWF therapy in the last 30 days or with the attainment of ADAMTS13 remission (partial [between 20% and LLN] or complete [≥LLN]), whichever occurs first.18

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aTTP=acquired thrombotic thrombocytopenic purpura; ISTH=International Society on Thrombosis and Haemostasis; iTTP=immune-mediated thrombotic thrombocytopenic purpura; LLN=lower limit of normal; MI=myocardial infarction; PEX=plasma exchange; TMA=thrombotic microangiopathy; TTP=thrombotic thrombocytopenic purpura; ULvWF=ultra-large von Willebrand factor; vWF=von Willebrand factor.

IMPORTANT SAFETY
INFORMATION AND INDICATIONS

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have

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IMPORTANT SAFETY
INFORMATION AND INDICATIONS

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have included urticaria.

WARNINGS AND PRECAUTIONS:

Bleeding Risk:
  • CABLIVI increases the risk of bleeding. Cases of major bleeding, including life-threatening and fatal bleeding have been reported in patients receiving CABLIVI, mainly in those using concomitant anti-platelet agents or anticoagulants. The risk of bleeding is increased in patients with underlying coagulopathies and concomitant use of CABLIVI with drugs affecting hemostasis.
  • In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of subjects. Overall, bleeding events occurred in approximately 58% of patients on CABLIVI versus 43% of patients on placebo.
  • If clinically significant bleeding occurs, interrupt use of CABLIVI. Von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If CABLIVI is restarted, monitor closely for signs of bleeding.
  • Withhold CABLIVI for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and CABLIVI is resumed, monitor closely for signs of bleeding.

ADVERSE REACTIONS:

The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).

CONCOMITANT USE OF ANTICOAGULANTS:

Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.

PREGNANCY:

There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

  • Fetal/neonatal adverse reactions: CABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.
  • Maternal adverse reactions: All patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnant women receiving CABLIVI should be carefully monitored for evidence of excessive bleeding.

INDICATIONS:

CABLIVI (caplacizumab-yhdp) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

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Instructions for Use

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References: 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2020. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. 3. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486-2495. doi:10.1111/jth.15006. 4. Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre. Am J Hematol. 2017;92(4):381-387. 5. Scully M, Hunt BJ, Benjamin S, et al. On behalf of British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335. 6. Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: national representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458. 7. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017;15(7):1448-1452. 8. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. 9. Masias C, Wu H, McGookey M, Jay L, Cataland S, Yang S. No major differences in outcomes between the initial and relapse episodes in patients with thrombotic thrombocytopenic purpura: the experience from the Ohio State University Registry. Am J Hematol. 2018;93(3):E73-E75. doi:10.1002/ajh.25002. 10. Schieppati F, Russo L, Marchetti M, et al. Low levels of ADAMTS-13 with high anti-ADAMTS-13 antibodies during remission of immune-mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: a multi-institutional study. Am J Hematol. 2020;95(8):953-959. doi:10.1002/ajh.25845. 11. Knoebl P, Cataland S, Peyvandi F, et al. Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. J Thromb Haemost. 2020;18(2):479-484. doi:10.1111/jth.14679. 12. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2017;130(14):1684. doi:10.1182/blood-2017-08-803171. 13. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3:17020. doi:10.1038/nrdp.2017.20. 14. Holz J-B. The TITAN trial—assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012;46(3):343-346. 15. Azoulay E, Bauer PR, Mariotte E, et al; Nine-i Investigators. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45(11):1518-1539. doi:10.1007/s00134-019-05736-5. 16. Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500-1511. doi:10.1182/blood-2009-09-243790. 17. Upreti H, Kasmani J, Dane K, et al. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood. 2019;134(13):1037-1045. doi:10.1182/blood.2019001056. 18. Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855-1861. doi:10.1182/blood.2020009150. 19. Vincent J-L, Castro P, Hunt BJ, et al. Thrombocytopenia in the ICU: disseminated intravascular coagulation and thrombotic microangiopathies—what intensivists need to know. Crit Care. 2018;22(1):158. 20. Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Hematology Am Soc Hematol Educ Program. 2018;2018(1):530-538. 21. Canpolat N. Hemolytic uremic syndrome. Turk Pediatri Ars. 2015;50(2):73-82. 22. Venugopal A. Disseminated intravascular coagulation. Indian J Anaesth. 2014;58(5):603-608. 23. Wada H, Matsumoto T, Suzuki K, et al. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Thromb J. 2018;16:14. 24. Cataland SR, Wu HM. How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome. Blood. 2014;123(16):2478-2484. 25. Laurence J, Haller H, Mannucci PM, Nangaku M, Praga M, de Cordoba SR. Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. Clin Adv Hematol Oncol. 2016;14 Suppl 11(11):2-15. 26. Supplement to: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. doi:10.1056/NEJMoa1806311. 27. Protocol for: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. doi:10.1056/NEJMoa1806311. 28. CABLIVI [instructions for use]. Cambridge, MA: Genzyme Corporation; 2019. MAT-US-2015992. 29. Centers for Medicare & Medicaid Services. Draft ICD-10-CM/PCS MS-DRGv28 Definitions Manual: MDC 8 Diseases & Disorders of the Musculoskeletal System & Connective Tissue Disorders. https://www.cms.gov/icd10manual/fullcode_cms/P0209.html. Accessed July 25, 2019. 30. Centers for Medicare & Medicaid Services. Department of Health and Human Services. 42 CFR Parts 405, 412, 413, 417, 476, 480, 484, and 495. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Final Policy Changes and Fiscal Year 2021 Rates; Quality Reporting and Medicare and Medicaid Promoting Interoperability Programs Requirements for Eligible Hospitals and Critical Access Hospitals Fed Regist. September 18, 2020;85(182):58432-59107. 31. Brodie S. Regulatory insight: Reviewing ICD-10-PCS Section X. ACDIS. Acdis.org website. https://acdis.org/resources/regulatory-insight-reviewing-icd-10-pcs-section-x. Accessed December 9, 2020. 32. Centers for Medicare & Medicaid Services. 2019 ICD-10-CM. https://www.cms.gov/Medicare/Coding/ICD10/2019-ICD-10-CM.html. Updated June 20, 2019. Accessed July 23, 2020. 33. Centers for Medicare & Medicaid Services. 2020 ICD-10-PCS. https://www.cms.gov/Medicare/Coding/ICD10/2020-ICD-10-PCS.html. Accessed July 25, 2020.