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Avatrombopag for Thrombocytopenia in CLD Patients: Efficacy and Safety Analysis

This journal club article reviews the use of avatrombopag, a TPO-R agonist, for managing thrombocytopenia in chronic liver disease (CLD) patients. The study discusses the common causes of thrombocytopenia in CLD, the mechanism of action of avatrombopag, and its comparison with other TPO-R agonists. The primary and secondary efficacy endpoints of the ADAPT-1 and ADAPT-2 trials are analyzed, along with safety profiles and complications. The study concludes with insights on efficacy, safety, treatment window, and identifies some potential shortfalls in study design related to the management of CLD patients with thrombocytopenia.

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Avatrombopag for Thrombocytopenia in CLD Patients: Efficacy and Safety Analysis

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  1. Journal Club February 2019 M. Thormann Gastroenterology 2018;155:705–718

  2. Thrombocytopenia in CLD patients • Common finding • Causes • Splenicsequestration • Increaseddestruction • Decreasedproductionofthrombopoietin • Myeloidsuppression • Platelettransfusionstopreventbleeding?

  3. Avatrombopag • TPO-R agonist (Mplbindingprotein) • Binding thetransmembranedomainof TPO receptor • First data 2004 • orallyadministered, for 5 days • Plateletadjusted dose • Similar: Eltrombopag, Romiplostim • Eltrombopagstudied in CLD patients • Lusutrombopag (7 days)

  4. ADAPT-1 & ADAPT-2

  5. ADAPT-1 & ADAPT-2 • Primary endpoint • Proportion ofpatients not requiring • Platelettransfusion • Rescueprocedureforbleeding • Secondaryefficacyendpoints • theproportionofpatientsachievingtargetplateletcountof > 50 on procedureday • thechange in plateletcountfrombaselinetoprocedureday Upto 7 days after procedure

  6. Selected procedures

  7. Results Proportion ofpatientswhoachievedplateletcounts > 50 on procedureday Proportion ofpatients not requiring a platelettransfusionoranyrescueprocedureforbleeding

  8. Results But: nodifference in bleedingevents Magnitude ofchange in plateletcountfrombaselinetoprocedureday.

  9. ADAPT-1 ADAPT-2

  10. Complications Overall safetyprofilesimilartoplacebo ADAPT-1 (high baseline): 2 deaths (not studyrelated) ADAPT-2 (high baseline): 1 partial portalveinthrombosis, day 13 (possiblyrelated) ADAPT-1 (lowbaseline): 1 portalveinthrombosis, day 31, receivedtransfusion (not related) (1 portalveinthrombosis in phase II)

  11. Conclusions Efficacy Safety Treatment window 10-13 days after first dose Shortfalls • Study design • onlyoneapplication • noprospectiveimagingincluded in protocol • Nodecrease in bleeding • qualityofthrombocytes • study design related?

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