Clinical review report : (Sanofi Genzyme, a division of Sanofi-Aventis Canada Inc.) : indication : indicated for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange (PEX) and immunosuppressive therapyCaplacizumab (Cablivi)

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious thrombotic microangiopathy. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and, sometimes, organ ischemia. Acquired TTP (aTTP), which is due to autoantibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) and is usually associated with an ADAMTS13 activity level of less than 10%, is the most common form of TTP (95%). The incidence of aTTP was reported in the literature to be 1.2 to 13 cases per million. In Canada, the number of patients with aTTP was estimated to be 173 in 2018.3 Since the development of therapeutic plasma exchange (PEX) or plasma infusion in the 1980s, mortality due to aTTP has decreased from 90% to a range of 10% to 20%. Early diagnosis and treatment of aTTP is essential to the patient's survival. Despite advances in understanding the disease and evolving treatment regimens, surviving patients with aTTP are still at risk for TTP exacerbation or relapse, refractory disease, or long-term consequences such as cognitive deficits, depression, hypertension, renal impairment, development of systemic lupus erythematosus, and reduced life expectancy. Daily PEX plus immunosuppressive therapies (primarily corticosteroids) are the mainstay of treatment. It allows removal of anti-ADAMTS13 antibodies and replenishment of functional ADAMTS13 and von Willebrand factor (vWF). PEX has substantially reduced mortality rates and enables faster remission in patients with aTTP although its use is associated with a number of adverse events (AEs). When there is a delay in delivering PEX, large-volume plasma infusions can be provided. Rituximab is another immunosuppressive that is also recommended for patients with aTTP, especially for those with refractory or relapsing aTTP, in conjunction with PEX and steroids; however, rituximab does not have an indication for aTTP. Refractory patients can also be treated with cytotoxic drugs such as cyclophosphamide, and splenectomy. Caplacizumab is a humanized, bivalent nanobody targeting the A1 domain of vWF to inhibit the interaction between vWF and platelets. On February 28, 2020, caplacizumab was approved by Health Canada for the treatment of adults with aTTP in combination with PEX and immunosuppressive therapy. The recommended dose of caplacizumab is as follows: 1. First day of treatment: 11 mg IV injection prior to PEX followed by an 11 mg subcutaneous injection after completion of PEX on that day.2. Subsequent days of treatment during PEX: daily 11 mg subcutaneous injection following PEX.3. Treatment after PEX period: 11 mg subcutaneous injections once daily for 30 days following the last daily PEX. If, after the initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels rema The CADTH Canadian Drug Expert Committee (CDEC) recommended that caplacizumab not be reimbursed for the treatment of adults with aTTP in combination with PEX and immunosuppressive therapy (March 6, 2020). A request for reconsideration was received by CADTH for this embargoed CDEC recommendation. The revised reimbursement criteria are for a narrower population: patients with multi-organ involvement indicating a more severe disease or refractory patients who do not respond well to previous treatment for a given time period, as determined by a specialist physician with expertise in treating aTTP..

Medienart:	E-Book

Erscheinungsjahr:	October 2020
Erschienen:	Ottawa (ON): Canadian Agency for Drugs and Technologies in Health ; October 2020
Ausgabe:	Final (with redactions).

Reihe:	CADTH common drug review

Sprache:	Englisch

Links:	www.ncbi.nlm.nih.gov [teilw. kostenfrei]

Themen:	Canada Immunosuppressive Agents Insurance, Health, Reimbursement Plasma Exchange Purpura, Thrombotic Thrombocytopenic Review Single-Domain Antibodies Treatment Outcome

Anmerkungen:	Includes bibliographical references. - Description based on online resource; title from PDF title page (viewed October 25, 2021)

Umfang:	1 online resource (1 PDF file (77 pages)) ; illustrations.

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1776329376