Should Caplivi (Caplacizumab) be discontinued based on ADAMTS13 (A Disintegrin and Metalloprotease with a Thrombospondin type 1 motif, member 13) levels?

From the Guidelines

Caplacizumab (Cablivi) therapy should be stopped when the ADAMTS13 activity level is normal, with an inhibitor or elevated anti-ADAMTS13 IgG, and the patient has shown clinical improvement, as indicated in the management of acquired TTP 1. When considering stopping Caplacizumab based on ADAMTS13 levels, it's crucial to assess both laboratory values and clinical status. The decision to discontinue treatment should be based on the patient's overall condition, including the normalization of ADAMTS13 activity and the absence of clinical symptoms.

• Key factors to consider when stopping Caplacizumab include:
  • ADAMTS13 activity level: Normalization of ADAMTS13 activity is a critical indicator of the effectiveness of treatment 1.
  • Clinical improvement: The patient should show significant clinical improvement, including the resolution of thrombocytopenia, anemia, and renal insufficiency 1.
  • Presence of inhibitor or elevated anti-ADAMTS13 IgG: The presence of an inhibitor or elevated anti-ADAMTS13 IgG is an important consideration when deciding to stop Caplacizumab 1. According to the guidelines for the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, Caplacizumab may be considered if ADAMTS13 activity level is normal, with an inhibitor or elevated anti-ADAMTS13 IgG 1.
• The management of acquired TTP involves a comprehensive approach, including:
  • Plasma exchange therapy: Initiation of therapeutic plasma exchange according to existing guidelines 1.
  • Corticosteroids: Administration of methylprednisolone 1 g IV daily for 3 days 1.
  • Rituximab: Consideration of rituximab for patients who have an initial platelet count response 1.
  • Caplacizumab: Discontinuation of Caplacizumab if the patient has shown clinical improvement and ADAMTS13 activity has normalized 1.

From the FDA Drug Label

If after initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remain present, treatment may be extended for a maximum of 28 days. Discontinue CABLIVI if the patient experiences more than 2 recurrences of aTTP, while on CABLIVI. The decision to stop caplacizumab (CABLIVI) based on ADAMTS13 levels is not directly addressed in the provided drug label. However, it is mentioned that treatment may be extended if signs of persistent underlying disease, such as suppressed ADAMTS13 activity levels, remain present.

• The label does not provide a specific ADAMTS13 level at which to stop treatment.
• It is recommended to discontinue CABLIVI if the patient experiences more than 2 recurrences of aTTP while on treatment 2. Therefore, the decision to stop CABLIVI based on ADAMTS13 levels should be made on a case-by-case basis, considering the individual patient's response to treatment and clinical presentation.

From the Research

Stopping Caplacizumab Based on ADAMTS13

• The decision to stop caplacizumab based on ADAMTS13 levels is a complex one, and the available evidence provides some guidance on this topic 3, 4, 5, 6, 7.
• ADAMTS13 is a von Willebrand factor-cleaving protease, and its deficiency is a key factor in the development of thrombotic thrombocytopenic purpura (TTP) 3.
• Caplacizumab is an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment that inhibits interaction between von Willebrand factor multimers and platelets 3.
• Studies have shown that caplacizumab is effective in reducing the time to normalization of platelet count, and the incidence of TTP-related death, recurrence of TTP, or thromboembolic events during the treatment period 3, 7.
• The HERCULES trial, a double-blind, controlled trial, found that patients who received caplacizumab had a shorter median time to normalization of platelet count, and a lower incidence of composite outcome events compared to those who received placebo 3.
• Another study found that caplacizumab may be used safely and effectively without concomitant plasma exchange in a patient with anaphylaxis to plasma 5.
• A systematic review and meta-analysis of eight studies found that caplacizumab was associated with a reduction in mortality, exacerbation, and refractory TTP, as well as a shorter time to platelet count recovery and length of therapeutic plasma exchange (TPE) 7.
• However, the same meta-analysis found that the bleeding rate was higher in the caplacizumab group, although the risk was generally modest and manageable 7.
• The current evidence suggests that caplacizumab can be stopped when ADAMTS13 activity is normalized, and the patient has achieved a stable clinical response 4, 6.
• A case report and updated literature review found that plasma exchange should be initiated within 6 hours of diagnosis, and caplacizumab can be added to the treatment regimen to improve outcomes 4.
• Another study found that a paradigm-changing scheme including caplacizumab, steroids, plasma exchange, rituximab, and intravenous immunoglobulins (CASPERI) was effective in inducing remission in patients with acute TTP 6.