This page contains a Flash digital edition of a book.
Immune Thrombocytopenia


Figure 2: Proportions of Patients with (A) Bleeding and (B) Clinically Significant Bleeding


A


100 80 60 40 20 0


On therapy Post-therapy


Eltrombopag increased and maintained platelet counts during the study period irrespective of splenectomy status, baseline platelet counts and concomitant ITP medication.55


By contrast, platelet counts


0 2 4 6 8 10121416 18 20 22 24 26 28 30 32 34 Study week


B


100 80 60 40 20 0


On treatment Post- treatment


remained low in patients receiving placebo, despite the use of rescue treatment in 40% of those participants. Patients assigned to eltrombopag were approximately eight times more likely to achieve target platelet counts ranging from 50–400x109/l (odds ratio [99% confidence interval] = 8.2 [3.59–18.73]; p<0.0001). In the eltrombopag group, the rates of bleeding (WHO grades 1–4) and clinically significant bleeding (WHO grades 2–4), see Figure 2, were reduced from baseline by roughly 50% from day 15 throughout the six-month treatment period. The rates returned to near baseline after discontinuation of eltrombopag.55


More than half of the eltrombopag-treated patients (37 out of 63 [59%]) were able to reduce concomitant treatment compared with 32% (10 out of 31) of the placebo patients (p=0.02). In addition, eltrombopag reduced the percentage of patients requiring rescue medications compared with placebo (18 versus 40%, respectively; p=0.001).55


012 4510 36 Placebo 14 18 Study week Eltrombopag


A: World Health Organization (WHO) grades 1–4. Source: Cheng et al., presented at the American Society for Hematology Annual Meeting 2008; B: WHO grades 2–4. Source: Cheng et al., 2011.55 393–402.


Figure 2B: Reprinted with permission from Elsevier, The Lancet, 2011;377:


returned to baseline levels during the six weeks of follow-up, as the platelet counts returned to near-baseline levels.51


Phase III Studies


This randomised, double-blind, placebo-controlled study enrolled 114 adults with chronic ITP and baseline platelet counts of <30x109/l. These patients were randomised to standard care plus either placebo (38 patients) or eltrombopag 50mg (76 patients) once daily for six weeks. The eltrombopag dose could be increased to 75mg in patients not responding after the initial three weeks of treatment. All patients had received prior ITP treatment and 52% had received at least three prior therapies.


The subsequent phase III trial (TRA100773B) demonstrated similarly positive results.54


At the end of the trial, 16% of placebo patients and 59% of eltrombopag patients achieved the primary end-point (platelet count ≥50x109/l), with median counts of 18x109/l in the placebo arm and 69x109/l in the eltrombopag arm.54


Importantly, there was a


significantly lower incidence of bleeding events during treatment with eltrombopag compared with placebo (p=0.029), with clinically significant bleeding (World Health Organization [WHO] grades 2–4) observed in fewer eltrombopag patients (16%) than placebo patients (36%).54


The RAndomized placebo-controlled Idiopathic thrombocytopenic purpura Study with Eltrombopag (RAISE) phase III trial that assessed the safety, efficacy and tolerability of eltrombopag in a long-term treatment setting (up to six months) has been completed.55 Adult patients with previously treated chronic ITP and who had baseline platelet counts <30x109/l were randomly allocated in a 2:1 ratio to eltrombopag (n=135) or placebo (n=62). The primary end- point was the odds of responding during the entire six-month treatment period.


68 22 26 1 2 4


Several other eltrombopag trials investigating the short- and long-term treatment of chronic ITP have been conducted, although results are only available in abstract form. Repeat ExPosure to Eltrombopag in Adults with Idiopathic Thrombocytopenic Purpura (REPEAT) was an open-label dose study involving three cycles of six weeks on treatment, followed by four weeks off treatment. This study assessed the safety and efficacy of repeated administration of eltrombopag.56


In the REPEAT study, response was maintained during episodic use with multiple courses of eltrombopag. In particular, by days eight and 15 of each cycle, >50 and >75% of patients had responded, respectively.


The Eltrombopag eXTENded Dosing (EXTEND) study is an open-label study for patients who have participated in previous eltrombopag trials and wish to take eltrombopag for the long-term treatment of their chronic ITP. This study is still active (see http://clinicaltrials.gov/ ct2/show/NCT00351468) and at the time of the latest analysis, 299 patients had received eltrombopag.57


The median duration of


eltrombopag treatment was 204 days (range: two to 861 days). At baseline, 33% of patients were receiving concomitant ITP medication and 38% had been splenectomised. Overall, 86% of patients (257 out of 299) had achieved platelet counts ≥50x109/l.57


Splenectomised and non-splenectomised patients responded equally well (89 and 82%, respectively) to eltrombopag. They responded regardless of baseline use of concomitant ITP medications. At baseline, 56% of patients reported bleeding symptoms (WHO grades 1–4) compared with 27, 21, 40 and 25% at six, 12, 18 and 24 months, respectively.57


In both trials, elevations in platelet counts and reductions in bleeding were associated with improvements in HRQoL across multiple domains, measures of fatigue and activities of daily living.


Improvements in HRQoL in the RAISE (and EXTEND) studies have been assessed with various validated tools (the Short Form 36 version 2 [SF-36v2]; the Functional Assessment for Chronic Illness Therapy [FACIT]-Fatigue subscale and six-item subset of the Functional Assessment of Cancer Therapy-Thrombocytopenia [FACT-Th] scale).58


EUROPEAN ONCOLOGY & HAEMATOLOGY


Proportion of patients with bleeding (%)


Patients with bleeding (%)


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92