*A conditional recommendation defined as desirable effects of the recommendation probably outweighing the undesirable effects. Assumes timely access to ADAMTS13 testing and clinical diagnosis based on high likelihood of aTTP/iTTP. In de novo patients where no reasonable access to ADAMTS13 activity testing is available, the Guidelines do not recommend CABLIVI; however, treatment of a patient previously diagnosed with aTTP/iTTP could be safely undertaken on clinical grounds without the need for a confirmatory ADAMTS13 test.3
†Acquired thrombotic thrombocytopenic purpura (aTTP) is also known as immune-mediated thrombotic thrombocytopenia purpura (iTTP). The terms can be used interchangeably.
ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; FDA=Food and Drug Administration; ISM=immunosuppressive medication; ISTH=International Society on Thrombosis and Haemostasis; MOA=mechanism of action; PEX=plasma exchange.
INFORMATION AND INDICATIONS
IMPORTANT SAFETY INFORMATION
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:
The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).
CONCOMITANT USE OF ANTICOAGULANTS OR ANTIPLATELET AGENTS:
Concomitant use of CABLIVI with any anticoagulant or antiplatelet agent may increase the risk of bleeding. Avoid concomitant use when possible. Assess and monitor closely for bleeding with concomitant use.
There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.
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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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. 29. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502. doi:10.1111/jth.15010 30. Centers for Medicare & Medicaid Services. ICD-10-CM/PCS MS-DRGv37 Definitions Manual: MDC 8 Diseases & Disorders of the Musculoskeletal System & Connective Tissue Disorders. https://www.cms.gov/icd10m/version37-fullcode-cms/fullcode_cms/P0213.html. Updated September 12, 2019. Accessed January 9, 2023. 31. Centers for Medicare & Medicaid Services. 2023 ICD-10-CM. https://www.cms.gov/files/zip/2023-code-tables-tabular-and-index.zip. Updated July 27, 2022. Accessed January 9, 2023. 32. Centers for Medicare & Medicaid Services. 2023 ICD-10-PCS. https://www.cms.gov/files/zip/2023-icd-10-pcs-code-tables-and-index.zip. Accessed January 9, 2023.