INTRODUCTION: Eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, non-peptide thrombopoietin receptor agonist developed as a treatment for thrombocytopenia of various etiologies, including chronic idiopathic thrombocytopenic purpura (ITP). In 2 placebo-controlled studies totaling over 200 patients with chronic ITP, eltrombopag has demonstrated a significant increase in platelet counts and a reduction in clinically relevant bleeding after up to 6 weeks of treatment. EXTEND is an ongoing open-label, phase III extension study to assess the long-term safety and efficacy of oral eltrombopag. Although the primary objective of this study was to raise platelet counts to a safe level (≥50,000/μL), the ability of eltrombopag treatment to allow patients to reduce concomitant ITP medications and avoid the adverse events associated with those therapies was also of interest.

METHODS: Adult patients with previously treated chronic ITP who completed a prior eltrombopag study were eligible to participate in EXTEND. Eltrombopag treatment was initiated at 50 mg once daily and then adjusted to maintain platelet counts ≥50,000/μL and <400,000/μL, with doses between 75 mg once daily and 25 mg once daily or less often than once daily, if necessary. The effect of eltrombopag treatment on the ability of patients to reduce and/or discontinue baseline concomitant ITP medications was evaluated.

RESULTS: As of the clinical cut-off date (January 7, 2008), 207 patients (median age, 50 years; 67% female) had received eltrombopag. At baseline, 69 (33%) patients reported the use of ITP medications; of these, 65 patients had at least 1 post-baseline visit by the clinical cut-off date and were evaluable for response status. Eighty percent (52/65) of these patients responded to eltrombopag with a platelet count of ≥50,000/μL during the study. Forty-eight percent (33/69) of patients attempted to reduce or discontinue their concomitant ITP medications during the study. Seventy percent (23/33) of these patients discontinued or had a sustained reduction of their baseline ITP medication and did not require any subsequent rescue treatment as of the clinical cut-off date; of these, 65% (15/23) had maintained the discontinuation or reduction for at least 24 weeks as of the clinical cut-off date. Sixty-one percent (20/33) of patients discontinued at least 1 baseline ITP medication, and 55% (18/33) discontinued all baseline ITP medications, without subsequent rescue treatment. Discontinued or reduced medications included prednisone (n = 11); prednisolone (n = 8); danazol (n = 5); and azathioprine, dexamethasone, mycophenolic acid, and oxymetholone (n = 1 each). Only 12% (8/69) of patients increased the dose of concomitant ITP medication from baseline.

CONCLUSION: In this study, long-term therapy with oral eltrombopag allowed 80% of patients with chronic ITP who were also receiving a concomitant ITP medication at baseline to maintain elevated platelet counts sufficient to permit a reduction in the use of concomitant ITP medications without the need for rescue therapy.

Disclosures: Fogarty:GlaxoSmithKline: Research Funding; GTC Biotherapeutics: Research Funding; Alexion Pharmaceuticals: Speakers Bureau; Baxter Bioscience: Honoraria. Bussel:GlaxoSmithKline: Equity Ownership, Honoraria, Research Funding. Cheng:GlaxoSmithKline: Consultancy, Honoraria. Bailey:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

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