ISTH Guidelines

ISTH TTP Guidelines are the first evidence-based, international
guidelines on the diagnosis, treatment, and management of aTTP^1,2

Who should not start Cablivi?

• Cablivi is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients
• Withhold Cablivi treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

^* 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. If ADAMTS13 testing is not available, do not add Cablivi.
^†The ISTH TTP Guidelines refer to aTTP as iTTP.

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.

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.

See aTTP—Diagnosis determined through clinical assessment¹

aTTP is a life-threatening blood disorder with considerable morbidity and mortality in the acute phase

Diagnose aTTP through clinical assessment or risk assessment tools prior to ADAMTS13 testing

Identifying aTTP is crucial for initiation of an appropriate therapeutic strategy

^*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. If AdamTS13 testing is not available, do not add CABLIVI.
^†List includes laboratory tests and results only; exclusive of physical symptoms, such as petechiae.
^‡ISTH did not appraise the evidence of these 2 tools.

Important safety information (cont’d) Warnings and Precautions:

• 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.

Treatment of relapses for a patient previously diagnosed with aTTP could be started safely based on clinical grounds without the need for a confirmatory AdamTS13 test

Who should not start Cablivi?

• Cablivi is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients
• Withhold Cablivi treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

^* 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. If AdamTS13 testing is not available, do not add Cablivi.

Important safety information (cont’d) 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.

These listings do not constitute an endorsement by Sanofi Genzyme and are not included in the ISTH Guidelines. The following is a selection of national laboratories offering AdamTS13 tests activity, inhibitor, and antibody testing. This is not an exhaustive list of labs that offer one or more of these tests or an endorsement of any lab. Other testing options may be available, including at local or regional laboratories. Content is current as of July 2020, and tests may not be available in all states. Please call laboratory to confirm test availability, sample shipping information, and all other logistics.

Prescribe Cablivi—the first and only FDA-approved, guideline-recommended therapy for aTTP in combination with PEX and immunosuppressive therapy

^* 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. If AdamTS13 testing is not available, do not add Cablivi.

Important safety information (cont’d) pregnancy:

• Pregnancy: There are no data on the use of caplacizumab in pregnant women. Studies in guinea pigs showed no effect of caplacizumab on the dams or foetuses. As a precautionary measure, it is preferable to avoid the use of Cablivi during pregnancy.
• Breastfeeding: There are no data on the use of caplacizumab in breastfeeding women. It is unknown whether caplacizumab is excreted in human milk. A risk to the child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to abstain/discontinue from therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.