Advances in the treatment of thrombotic thrombocytopenic purpura: repurposed drugs and novel agents

ABSTRACT

Introduction

Thrombotic thrombocytopenic purpura (TTP) is an infrequent but fatal disease. Plasma exchange and corticosteroids continue to be the mainstay of treatment; however, repurposed drugs and novel agents are emerging as efficient treatment options.

Areas covered

In this review, new therapeutic developments in immune-mediated TTP including rituximab, bortezomib, N-acetylcysteine, caplacizumab, and recombinant ADAMTS13, among others, are summarized.

Expert opinion

Evidence on the use of rituximab in first and second-line settings is accumulating showing promising potential for avoiding relapses in patients in remission but with low circulating levels of ADAMTS13 in a preemptive fashion. Other repurposed drugs such as bortezomib and N-acetylcysteine are increasingly used off-label. Recombinant ADAMTS13 is slowly emerging. Caplacizumab, a humanized anti-von Willebrand factor-directed nanobody that blocks platelet adhesion and avoids microthrombi formation, was approved by regulatory agencies based on the positive results of a phase-III clinical trial, adding a new drug to the therapeutic arsenal in TTP.

KEYWORDS:

• Thrombotic Thrombocytopenic Purpura
• treatment
• therapeutic plasma exchange
• rituximab
• caplacizumab
• N-acetylcysteine
• novel agents

Article highlights

• Plasma exchange remains the cornerstone of treatment in immune-mediated thrombotic thrombocytopenic purpura.

• Rituximab is safe and has been associated to a low relapse rate in uncontrolled studies for newly diagnosed and relapsed patients. Its use as pre-emptive therapy triggered by low ADAMTS13 levels is promising.

• Bortezomib and N-acetylcysteine have been repurposed for this indication and used off-label with clinical experience accumulating.

• Caplacizumab, a von Willebrand factor-directed nanobody has been added to the therapeutic arsenal following the positive results of the phase-III HERCULES trial.

• Caplacizumab in addition to plasma exchange achieves earlier platelet count recovery and reduces the event rate of a composite outcome including TTP-related death, recurrence or major thromboembolic event

• The results of clinical trials using magnesium sulfate, anti-IgG, and recombinant ADAMTS-13, are awaited

Acknowledgments

The authors thank Dr. S Lozano for revising this manuscript

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.