Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia

Clin Pharmacol Ther. 2015 Feb;97(2):186-93. doi: 10.1002/cpt.17. Epub 2014 Dec 20.


Using data from a large commercial health insurer, we studied prescribing of romiplostim (Nplate) and eltrombopag (Promacta), two drugs for primary immune thrombocytopenia (ITP) for which risk evaluation and mitigation strategies (REMS) with elements to assure safe use were initially imposed and then removed. We identified 103 and 117 new users of romiplostim and eltrombopag, respectively. Use was almost exclusively for FDA-approved indications ("on-label") while the REMS with elements to assure safe use were in place. After these elements were lifted, off-label use of eltrombopag among patients with hepatitis C virus (HCV), a subsequently approved indication, increased. The ratio of incidence rate ratios of off-label/HCV to on-label initiation of eltrombopag between the two time periods was significant (13.41; P < 0.001). Our finding of an association with reduced off-label prescribing suggests that REMS with elements to assure safe use can help promote patient safety but may also prevent promising off-label drug uses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzoates / therapeutic use*
  • Female
  • Hepatitis C / drug therapy*
  • Humans
  • Hydrazines / therapeutic use*
  • Male
  • Middle Aged
  • Off-Label Use / statistics & numerical data*
  • Patient Safety
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Pyrazoles / therapeutic use*
  • Receptors, Fc / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Retrospective Studies
  • Risk Assessment*
  • Risk Reduction Behavior*
  • Thrombopoietin / therapeutic use*
  • United States
  • Young Adult


  • Benzoates
  • Hydrazines
  • Pyrazoles
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • Thrombopoietin
  • romiplostim
  • eltrombopag