Management of chronic ITP:

TPO-R agonist vs Immunosuppressant

PUTU NIKEN AYU AMRITA

HEMATOLOGY AND MEDICAL ONCOLOGY DIVISION
INTERNAL MEDICINE DEPARTMENT
AIRLANGGA SCHOOL OF MEDICINE- DR SOETOMO TEACHING HOSPITAL
Topics List

 Introduction
 Unmet needs in adult chronic ITP management
 Thrombopoietin receptor (TPO-R) agonists: rationale and
mechanism of action
 TPO-R agonis Rebozet clinical trials
 Summary
Introduction

 Most adult with ITP (60%), even if initially responded to steroid  chronic ITP
 Even mild thrombocytopenia  affect quality of life, bruising, mucosal bleeding and fatigue,
 Other treatment options after CS: splenectomy, rituximab, TPO agonist, immunosupresant
 1/3-2/3 of chronic ITP patients  partial or complete remission after several years
 Affects the choice of therapy, decision to recommend or wait for a splenectomy

1 Stasi R, Provan D. Mayo Clin Proc 2004; 79: 504–22; 2. Profit L. Core Evidence 2006; 1: 221–31;
3. George J. Thromb Haemost 2006; 4: 1664–72
 There is no marker that can reliably predict a chronic course.

 10 years ago, the risk of severe bleeding 3% in children and over 70% in older adults (> 60 years), the
risk of fatal bleeding, at 0% and 13%, respectively

 Due to reduced prescriptions and the new thrombopoietin receptor agonists (TRAs), the prognosis has
improved significantly in recent years
Summary of recommendations

Management of adults with ITP ≥ 3 months who

Management of adults with ITP < 3 months
are dependent on or unresponsive to
First-line management strategy corticosteroids
01 If platelet count ≥ 30 x 109/L, observation is Second-line management strategy
recommended If platelet count < 30 x 109/L, steroids are 07 08 09
suggested TPO-RAs > rituximab > splenectomy

02 Outpatient or inpatient management

If platelet count ≥ 20 x 109/L, outpatient management is
suggested If platelet count < 20 x 109/L, hospital admission is
suggested
Duration of corticosteroids
03 Prednisone < 6 weeks is recommended (including tapering)
06
Patients for whom TPO-RAs are considered
Eltrombopag or romiplostim is suggested

Type and dosage of corticosteroids

04 Prednisone (0.5–2.0 mg/kg/day) for < 6 weeks or
dexamethasone (40 mg/day) for 4 days is suggested

Role of rituximab in first-line

05 Corticosteroids > corticosteroids + rituximab

American Society of Hematology 2019 guidelines for immune thrombocytopenia

Individualized selection of second-line therapy in adults
based on shared decision-making

Adult with ITP > 3 months

3–12 months Assess duration of ITP > 12 months

TPO-RAs TPO-RAs
Rituximab Rituximab
Splenectomy
Assess patient values and
preferences Assess patient values

Patient wishes to achieve Patient wishes to avoid Patient wishes to achieve a Patient wishes to avoid Patient wishes to avoid
a durable response long-term medication durable response long-term medication surgery

TPO-RAs Rituximab TPO-RAs Rituximab TPO-RAs

Splenectomy Splenectomy Rituximab

Patient characteristics a
Patient Patient Patient Patient Patient Patient
Actions
wishes to wishes to wishes to wishes to wishes to wishes to
Treatment options avoid avoid avoid achieve achieve avoid
surgery long-term surgery a a long-term
medication durable durable medicatio
response response n
TPO-RAs Splenectomy Rituximab Splenectomy TPO-RAs
a Other factors that might influence treatment decisions include frequency of bleeding
sufficient to require hospitalization or rescue medication, comorbidities, compliance, Rituximab
Adapted from Management of Immune Thrombocytopenia. A pocket guide for the clinician. Available from:
medical and social support networks, cost, and availability of treatments. www.hematology.org/Clinicians/Guidelines-Quality/Documents/10115.aspx. Accessed 9 January 2020.
Traditional first-line treatment options are limited by lack of long-term response

Corticosteroids:
 Although many patients (50–90%) initially respond,1 only 15% maintain this response (over the subsequent 6–12
months)2
 Tolerability reduces with repeat dosing3
 Side effects can often outweigh benefits3
IVIg:
 IVIg is often used when a rapid increase in platelets is required in emergency situations 4
 However, responses are usually transient, lasting 2–4 weeks3
 In addition, side effects such as headaches can be severe 3

In patients who have an insufficient response to first-line therapy, there is a

need for a treatment option with an acceptable benefit-risk profile
IVIg, intravenous immunoglobulin.
1. Cines DB, Bussel JB. Blood 2005; 106: 2244–51; 2. McCrae K, et al. Cleve Clin J Med 2011; 78: 358–73; 3. Provan D, et al. Blood 2010; 115: 168–86; 4. Neunert et al.
Blood 2011; 117: 4190–4207.
Second-line treatment options for adult chronic ITP

Splenectomy • Irreversible procedure that many patients are reluctant to undergo 1

• Associated with complications including bleeding and infection 2
• Initial response rate: 80%2
• However, approximately one-third of these patients fail to achieve
a sustained response, and there are no definitive pre-operative
characteristics predictive of response2

Rituximab • Not licensed for the treatment of chronic adult ITP 3

• Initial response rate: 60%4,5
• Long-term (5-year) response: 21%6
• Serious reactions can occur2

• With the availability of TPO-R agonists and the long-term responses these may
induce, the use of splenectomy has been falling 7
• These agents show high efficacy and an acceptable benefit-risk profile, even in
refractory patients7

TPO-R, thrombopoietin receptor.

1. Cines DB, Bussel JB. Blood 2005; 106: 2244–51; 2. Provan D, et al. Blood 2010; 115: 168–86; 3. Rituximab SmPC; 4. Arnold DM, et al. Ann Intern Med 2007; 146: 25–
33; 5. Auger S, et al. Br J Haematol 2012; 158: 386–98; 6. Patel VL, et al. Blood 2012; 119: 5989–95; 7. Provan D, Newland AC. Adv Ther 2015; 32: 875–887.
 Traditional ITP treatments with ‘historic’ medical approvals
(azathioprine, cyclophosphamide, Vinca) or treatments without
medical approval should only be used after failure of steroids,
Immunosuppresant
TRAs, and rituximab.

‘Historic’ means that these agents were licensed in the 1970s or 1980s before current standards
of Good Clinical Practice and Evidence-Based Medicine were implemented.

Matzdorff/Meyer/Ostermann/Kiefel/Eberl/Kuhne/Pabinger/Rummel. Immune Thrombocytopenia – Current Diagnostics andTherapy:

Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTIOncol Res Treat 2018;41(suppl 5):1–30
 The patient’s perspective:
effect of ITP treatments
• The patient’s perspective on treatment effects is important for
decision-making1
• Web-based questionnaire of 122 adults with chronic ITP:2
Steroids2
30/122 (25%) were taking steroids during the 3-month period prior to the survey
• Most commonly reported side effects:
• weight gain (48%)
• moon face (46%)
• personality changes/mood swings (36%)
• 69% said they would only take steroids if there were no other options available
• 17% said they would not take steroids any more at all

Rituximab2 Splenectomy2
27/122 (22%) had been treated with 33/122 (27%) had been splenectomised
rituximab • 58% would advise other patients
• 7% reported severe infusion reactions against this procedure
• 52% said they would try to avoid/refuse • 42% had received subsequent
rituximab in the future treatment with rituximab, IVIg etc.
IVIg, intravenous immunoglobulin
1. Mathias S, et al. Health Qual Life Outcomes 2008; 6: 13; 2. Matzdorff AC, et al. PLoS One 2011; 6: e27350
 Patients and physicans consider side effects of steroid
treatment burdensome
80 How patients and physicians rate steroid side effects:

Moon face Patient

Hematologist
70 * Weight gain
*p<0.05 hematologist vs patient

60

Insomnia
50
* Anxiety Fatigue
Percent

Depression High blood sugar levels

40 * Pain
Irritability *
*
* * *
Hot flushes
30
Hair loss *
Vision
Acne
*
20 Nausea
* *
Dizziness
* * High blood pressure
10

0 Depression
Anxiety
Moon face

Hair loss

Insomnia

Irritability

Muscle
Acne

weakness
Stretch
marks

Dizziness
Nausea

High blood
pressure
Blood
glucose
Visual
Tiredness

problems
Body pain
Weight gain

Hot flushes
Figure reproduced from Guidry JA et al. Eur J Haematol 2009; 83: 175-82
Thrombopoietin (TPO)

Stem cell • TPO is a potent endogenous

TPO haematopoietic growth factor that
plays an integral role in platelet
Bilineal progenitor cell
production1-3
TPO – Primarily produced in the liver1
Committed megakaryocyte
progenitor cell – Influences proliferation/differentiation
TPO
of megakaryocytes2
• Drives platelet production via the TPO
Immature megakaryocyte
receptor (TPO-R)4
TPO
• Decline in platelet mass causes an
Mature megakaryocyte increase in TPO levels to maintain
platelet levels
– TPO levels usually remain elevated
Platelets
during any incident of persistent
thrombocytopenia1
1. Kuter D, et al. Blood 2002; 100: 3456–69; 2. Kaushansky K. N Engl J Med 1998; 339: 746–54; 3. Wolber E, Jelkmann W. News Physiol Sci 2002; 17: 6–10;
4. Kuter D, et al. Blood 2007; 109: 4607–16. Figure adapted from Kaushansky K. N Engl J Med 1998; 339: 746–54.

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 Rebozet mechanism of action

TPO Agonist

TPO-R
TPO-R active
inactive

p p

SHC GRB2
SOS
Cell membrane JAK
RAS/RAF

STAT MAPKK

Cytoplasm P42/44

Signal transduction

Increased platelet production

Figure adapted from Kuter D. Blood 2007; 109: 4607–16.

©
 Summary of Rebozet clinical experience in adult chronic ITP
No. patients
Study receiving
Description Dose Primary endpoint
reference Rebozet/total no.
patients
Phase II, randomised, double-blind, placebo-controlled trial
TRA100773A1 Rebozet at 30, 50, or Increase in platelet counts ≥50
88/117 examining once-daily oral treatment with Rebozet in adults
NCT00102739 75 mg for 6 weeks x 109/L
with chronic ITP
Phase III, randomised, double-blind, placebo-controlled
TRA100773B2 Starting dose 50 mg daily, Increase in platelet counts ≥50
76/114 study examining once-daily oral treatment with Rebozet in
NCT00102739 titrated as necessary x 109/L
adults with chronic ITP
RAISE3 Phase III, randomised, double-blind, placebo-controlled Starting dose 50 mg daily, Odds of achieving platelet
135/197
NCT00370331 study in adults with chronic ITP titrated as necessary counts 50–400 x 109/L
REPEAT4 Phase II, open-label, repeated 6-week dosing study in
66/66 Starting dose 50 mg daily Consistency of response
NCT00424177 adults with chronic ITP
EXTEND5,6 Phase III, open-label extension study in adult patients with Starting dose 50 mg daily, Long-term safety and
302/302
NCT00351468 chronic ITP who had completed a previous Rebozet study titrated as necessary efficacy
Bone marrow Bone marrow fibre changes
Phase IV, open-label, 2 -year safety post-approval Starting dose 50 mg daily,
study7,8 167/167 after 1 and 2 years of
commitment study in adults with chronic ITP titrated as necessary
NCT01098487 treatment
Observational study monitoring ocular safety in subjects
LENS9 Long-term ocular safety with
164/164 previously enrolled in a Rebozet trial and who received N/A – observational only
NCT00643929 respect to changes in the lens
either Rebozet or placebo

1. Bussel J, et al. N Engl J Med 2007; 357: 2237–47; 2. Bussel J, et al. Lancet 2009; 373: 641–8; 3. Cheng G, et al. Lancet 2011; 377: 393–402. Erratum in Lancet 2011;
377: 382; 4. Bussel J, et al. Br J Haematol 2013; 160: 538–46; 5. Saleh, et al. Blood 2013; 121: 537–45; 6. Bussel J, et al. Blood 2013; 122: Abstract 2315;
7. ClinicalTrials.gov. NCT01098487. Available from: http://clinicaltrials.gov/ct2/show/NCT01098487 [Accessed December 2015]; 8.  Brynes RK, et al. EHA 2013 Abstract
P465; 9. ClinicalTrials.gov. NCT00643929. Available from: http://clinicaltrials.gov/ct2/show/NCT00643929 [Accessed December 2015].
RAISE

Primary endpoint: proportion of responders* significantly

greater with Rebozet vs control

~8x greater odds of achieving platelet response throughout the

6-month treatment period with Rebozet vs control
OR 8.2, 99% CI: 3.59, 18.73; p<0.0001
100

Patients responding to
90 Rebozet
80 Control
treatment (%)
70 On treatment Post-
treatment
60
50
40
30
20
10
0
Week 0 1 2 3 4 5 6 10 14 18 22 26 1 2 4
Number of Control 61 60 60 59 60 60 59 47 50 48 47 58 54 55 58
patients Rebozet 135 134 133 133 131 134 134 108 114 112 113 132 110 118 119

• 79% of patients responded to Rebozet at least once (vs 28% in the control group; p<0.0001)
*Response to treatment defined as a platelet count of 50–400 x 109/L. CI, confidence internal; OR, odds ratio.
Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.
Figure reproduced from Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382

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 RAISE

Rebozet treatment rapidly increased and maintained median platelet counts

• Early response: median platelet counts more than doubled in the first
week of Rebozet treatment (rising from 16 x 109/L to ~36 x 109/L)
• Sustained response: median platelet counts remained above 50,000/μL
from Week 2 until the end of the treatment period

140 On treatment Post-

treatment
Median platelet count

120
per µL (x 103)

100
80
60
40
20
0
Study week 0 1 2 3 4 5 6 10 14 18 22 26 1 2 4
Number of Control 61 60 59 58 59 59 58 43 46 44 43 53 54 55 58
Rebozet 135 134 131 129 123 128 128 96 101 95 91 110 110 118 119
patients

Rebozet
Cheng G, et al. Lancet 2011; 377: 393-402. Erratum: Lancet 2011; 377: 382.
Figure reproduced from Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382. Control
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 RAISE
Rebozet treatment reduced bleeding and clinically significant bleeding vs
control

50 On treatment Post- Rebozet

clinically significant bleeding

treatment Control

Proportion of patients with

(WHO Grades 2–4) (%)

40

30

20

10

0
0 1 2 3 4 5 6 10 14 18 22 26 1 2 4
Study week

Reductions in bleeding were associated with improvements in

quality of life

World Health Organization (WHO) Bleeding Scale: Grade 2, mild blood loss; Grade 3, gross blood loss; Grade 4, debilitating blood loss.
Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.
Figure reproduced from Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.

©
 RAISE

Rebozet was generally well tolerated

AEs in ≥10% of patients regardless of causality: 17 patients discontinued

Control Rebozet treatment early due to AEs
AE, n (%)
(n=61) (n=135) • 13 patients in the Rebozet group: ALT
increased (n=4); TEE (n=2); cataract,
Any AE regardless of causality duodenal-ulcer haemorrhage, urticaria,
56 (92) 118 (87)
Headache rash, tachycardia, headache and
20 (33) 41 (30)
Diarrhoea rectosigmoid cancer (n=1 for each)
6 (10) 17 (13)
Nausea • 4 patients in the control group: cataract
4 (7) 16 (12)
Nasopharyngitis (n=2); fatal brain-stem haemorrhage
8 (13) 14 (10) (n=1); abnormal renal function test
Upper respiratory tract
7 (11) 14 (10) results, ALT increased, or
infection
8 (13) 13 (10) hyperkalaemia (n=1)
Fatigue
6 (10) 9 (7)
Limb pain
6 (10) 7 (5)
Epistaxis Grade 3 or 4 (severe or
6 (10) 5 (4)
Dizziness
6 (10) 2 (1) life-threatening) AEs
Peripheral oedema
• Most grade 3 or 4 AEs in the control
Any grade 3 or 4 AE* 7 (11) 20 (15) group were bleeding events
Deaths 1 (2) 0 • Only 2% of patients in the Rebozet
group had grade 3 or 4 bleeding
events
control
*Severity of adverse events, including bleeding adverse events, was reported according to National Cancer Institute Common 7%
Terminology Criteria for Adverse Events
(version 3.0); AE, adverse event; ALT, alanine aminotransferase; TEE, thromboembolic event.
Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.
Table reproduced from Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.

©
 RAISE

Safety events of special interest

• Two patients receiving Rebozet had on-treatment thromboembolic events

• Hepatobiliary laboratory abnormalities were observed in a small number
of patients:
– ALT increased to ≥3x ULN: nine patients in the Rebozet group and
two patients in the control group
• All resolved either whilst on treatment or after discontinuation
– Total bilirubin increased to >1.5x ULN in five (4%) patients in the
Rebozet group and none in the control group
• One patient from each of the Rebozet and control groups withdrew from the
study due to increases in ALT
• No clinically significant differences between groups were noted in
progression of existing or formation of new cataracts or malignant disease

ALT, alanine aminotransferase; ULN, upper limit of normal.

Cheng G, et al. Lancet 2011; 377: 393–402. Erratum: Lancet 2011; 377: 382.
 EXTEND

Study design

• Eltrombopag eXTENded Dosing (EXTEND) was an open-label safety and efficacy

study of long-term treatment of adult patients with chronic ITP who had an insufficient
response to ≥1 previous ITP treatment and who had previously completed a Rebozet
study1,2
Sequential dose adjustment
Prior Rebozet studies to achieve target platelet count
RAISE study Rebozet dosing initiation
6 months’ treatment (≥100,000/µL)**

Minimise concomitant
REPEAT study
ITP medications
Intermittent treatment Initiate dosing
302 patients (maintain ≥50,000/µL)††
Screening at 50 mg per
enrolled
day
773A study Optimise Rebozet dosing
6 weeks’ treatment (maintain ≥50,000/µL)

Maintenance dosing
773B study
(maintain platelet counts
6 weeks’ treatment
≥50,000/µL)

Patients were permitted to use local stable maintenance standard of care; *≥50,000/µL in patients not receiving concomitant ITP medications at baseline;
†
Only required for patients receiving concomitant ITP medications at baseline.
1. Saleh M, et al. Blood 2013; 121: 537–45; 2. Bussel J, et al. Blood 2013; 122: Abstract 2315.
Figure adapted from Saleh M, et al. Blood 2013; 121: 537–45 Supplementary materials.

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 EXTEND

High response rates were seen with up to 8.76 years of follow-up

Proportion of patients achieving platelet counts

≥50,000/μL at least once during treatment in the
absence of rescue therapy
100
90

85.8%
80
70
60 of patients responded* to Rebozet at least once
Patients (%)

50 during treatment1
40
30 Similar responses to Rebozet treatment were observed
irrespective of splenectomy status2 or use of concomitant
20
ITP medications at baseline1
10
0
Revolade
n=259/302

• 61% of patients achieved a platelet count ≥50,000/μL in the absence of rescue medications at
≥50% of on-treatment assessments1

*A response was defined as a platelet count ≥50,000/µL at least once during the study, in the absence of rescue medications. These data include patients with a platelet count
>50,000/µL at baseline (n=39).
1. Data on file; 2. Wong et al. Abstract EHA-1793, accepted for presentation at the 21st Congress of the European Hematology Association, Copenhagen, June 9–12, 2016.
 REPEAT

Study design

Phase II, open-label, single-arm, repeat-dose study in adult patients with

chronic ITP
• Objective: to evaluate the consistency of response and safety of repeated
6-week dosing of Rebozet with 4-week off-study intervals in patients with chronic ITP
• Dosing: 50 mg once daily over three cycles of repeated, intermittent administration
• Primary endpoint: The proportion of patients who responded to Rebozet treatment in
Cycles 2 or 3, given a response in Cycle 1. Response was defined as platelets ≥50 x
109/L and 2x baseline at Day 42 of each treatment cycle

Cycle 1 Cycle 2 Cycle 3

ITP patients with
platelet counts Up to 6 Up to 4 Up to 6 Up to 4 Up to 6 Up to 4
20–50 x 10 /L* 9 weeks on weeks off weeks on weeks off weeks on weeks off
therapy therapy therapy therapy therapy therapy

Dose increase from Rebozet 50 to 75 mg was permitted on or after Day 22 in patients whose platelet counts were <50 x 109/L for 2 consecutive weeks (this dose would
then be continued in subsequent cycles).
*Patients with platelet counts outside 20–50 x 109/L were included in the primary analysis if they were defined as a responder in Cycle 1.
Bussel J, et al. Br J Haematol 2013; 160: 538–46.
 REPEAT

Study design

Phase II, open-label, single-arm, repeat-dose study in adult patients with

chronic ITP
• Objective: to evaluate the consistency of response and safety of repeated
6-week dosing of Rebozet with 4-week off-study intervals in patients with chronic ITP
• Dosing: 50 mg once daily over three cycles of repeated, intermittent administration
• Primary endpoint: The proportion of patients who responded to Rebozet treatment in
Cycles 2 or 3, given a response in Cycle 1. Response was defined as platelets ≥50 x
109/L and 2x baseline at Day 42 of each treatment cycle

Cycle 1 Cycle 2 Cycle 3

ITP patients with
platelet counts Up to 6 Up to 4 Up to 6 Up to 4 Up to 6 Up to 4
20–50 x 10 /L* 9 weeks on weeks off weeks on weeks off weeks on weeks off
therapy therapy therapy therapy therapy therapy

Dose increase from Rebozet 50 to 75 mg was permitted on or after Day 22 in patients whose platelet counts were <50 x 109/L for 2 consecutive weeks (this dose would
then be continued in subsequent cycles).
*Patients with platelet counts outside 20–50 x 109/L were included in the primary analysis if they were defined as a responder in Cycle 1.
Bussel J, et al. Br J Haematol 2013; 160: 538–46.
REPEAT

Repeated intermittent use of Rebozet produced consistent and

sustained platelet increases across multiple treatment cycles
Off

Median platelet count (x 109/L)

250 On therapy Cycle 1
therapy Cycle 2
200 Cycle 3

150

100

50

1 8 15 22 29 36 43 50 57 64 71
Study day
• Following an interruption in treatment, a high proportion of patients responded to
Rebozet at similar doses to those used in previous cycles
– Repeated short-term use of Rebozet may be effective in situations where constant therapy
is not required
Error bars represent the 25th to 75th percentiles for each treatment group.
Bussel J, et al. Br J Haematol 2013; 160: 538–46. Figure reproduced from Bussel J, et al. Br J Haematol 2013; 160: 538–46.

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 REPEAT

Repeated intermittent administration of Rebozet was generally well tolerated

Adverse events (AEs) reported Patients, n (%)

by ≥9% of patients
All cycles on therapy (n=66) All cycles off therapy (n=65)

Any AE 45 (68) 41 (63)

Headache 14 (21) 5 (8)
Diarrhoea 7 (11) 4 (6)
Fatigue 6 (9) 6 (9)
Nasopharyngitis 6 (9) 6 (9)

• The frequency of AEs during on-therapy periods was similar to off-therapy periods
• The AEs reported were consistent with those seen in other Rebozet studies

Bussel J, et al. Br J Haematol 2013; 160: 538–46.

THANK YOU
4 YOUR KIND
ATTENTION
Rebozet: dose adjustments

Recommended starting dose in adults:*

25 mg once daily

Wait 2 weeks

<50,000/µL ≥50,000/µL to ≤150,000/µL >150,000/µL to ≤250,000/µL >250,000/µL

Increase Maintain Decrease Stop

dose by 25 mg to a use lowest dose or dose by and increase the frequency of
maximum of 75 mg/day† concomitant ITP 25 mg/day‡ platelet monitoring to twice
treatment weekly. Once the platelet count
is <100,000/μL, reinitiate
therapy at a daily dose reduced
Reassess in 2 weeks Reassess in 2 weeks
by 25 mg/day‡

*For patients of East-Asian ancestry, Rebozet should be initiated at a reduced dose of 25 mg once; †For patients taking 25 mg once every other day, increase dose to
25 mg once daily; ‡For patients taking 25 mg once daily, consideration should be taken to dosing at 12.5 mg once daily, or 25 mg once every other day.
Eltrombopag Global Data Sheet. Version 12. March 2016.
Therapies for the treatment of ITP -Overview

3rd-line
munosuppressan
Matzdorff A, et al. Oncol Res Treat. 2018;41(suppl 5):1-30.
Summary

 Chronic ITP 