Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP

Area of Science:

• Hematology
• Immunology
• Pharmacology

Background:

• Current immune-mediated thrombotic thrombocytopenic purpura (iTTP) treatments, including therapeutic plasma exchange (TPE), corticosteroids, rituximab, and caplacizumab, have improved outcomes.
• However, prolonged caplacizumab use is often necessary due to persistent ADAMTS13 deficiency, raising cost and tolerance issues.

Purpose of the Study:

• To determine if anti-ADAMTS13 antibody titers and their trajectory during the acute phase predict ADAMTS13 improvement.
• To identify potential strategies for optimizing immunosuppression to shorten recovery time in iTTP patients.

Main Methods:

• Retrospective analysis of 286 iTTP patients treated with a triplet regimen.
• Evaluation of anti-ADAMTS13 IgG antibody titers and ADAMTS13 activity at diagnosis and during the acute phase post-TPE.
• Validation in an independent cohort of 51 iTTP patients.

Main Results:

• A baseline anti-ADAMTS13 IgG antibody cutoff of 90.5 U/mL showed modest predictive ability for long-term response.
• Patients whose anti-ADAMTS13 IgG antibody titers decreased within 7-14 days post-TPE showed significantly higher rates of ADAMTS13 activity improvement (65%) compared to those without a decrease (25%).
• This finding was confirmed in a validation cohort.

Conclusions:

• The trajectory of anti-ADAMTS13 antibody titers, particularly a decrease within the first two weeks post-TPE, is a valuable predictor of ADAMTS13 activity recovery in iTTP.
• Early intensification of immunosuppression, guided by antibody titer monitoring, may shorten the time to ADAMTS13 recovery and potentially reduce the need for extended caplacizumab treatment.
• Monitoring anti-ADAMTS13 antibodies can inform immunomodulatory strategies, including the judicious use of B-cell depleting agents.