Immune thrombocytopenia

Section editors
	Shruti Chaturvedi, MBBS, MSCI Baltimore, MD LinkedIn		Benjamin Tillman, MD Nashville, TN

20 regimens on this page 30 variants on this page

Guidelines

ASH

• 2011: The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia

Initial therapy

Dexamethasone monotherapy

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Variant #1

Study	Evidence	Comparator	Efficacy
Wei et al. 2015	Phase III	Prednisone	Superior CR rate

Immunosuppressive therapy

• Dexamethasone (Decadron) 40 mg/day PO on days 1 to 4

One course

If platelets remained below 30 x 10⁹/L or bleeding by day 10, course is repeated once.

Variant #2

Study	Evidence	Comparator	Efficacy
Matschke et al. 2013	Phase III	Prednisone	Seems not superior

Immunosuppressive therapy, part 1

• Prednisone (Sterapred) 1 mg/kg/day for 7 days

Immunosuppressive therapy, part 2

• Dexamethasone (Decadron) 0.6 mg/kg/day for days 1 to 4

21-day cycle for 6 cycles

Variant #3

Study	Evidence
Cheng et al. 2003	Phase II

Immunosuppressive therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

4-day course

Patients who had an initial response, but whose platelets dropped below 30 x 10⁹/L within 6 months received:

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Prednisone (Sterapred) 15 mg PO once per day starting on day 5, "with gradual tapering"

Variant #4, monthly dexamethasone

Study	Evidence
Mazzucconi et al. 2007	Phase II

Immunosuppressive therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Patients who had platelet counts of less than or equal to 20 x 10⁹/L between cycles received Prednisone (Sterapred) 0.25 mg/kg PO once per day "between courses"

28-day cycle for 6 cycles

Variant #5, bi-weekly dexamethasone

Study	Evidence
Mazzucconi et al. 2007	Phase II

Immunosuppressive therapy

• Dexamethasone (Decadron) as follows:
  • Adults: 40 mg PO/IV once per day on days 1 to 4
  • Patients less than 15 years old: 20 mg/m² (maximum dose: 40 mg per day) PO/IV once per day on days 1 to 4
  • Patients who had platelet counts of less than or equal to 30 x 10⁹/L between cycles and/or who had bleeding related to thrombocytopenia received 0.035 mg/kg PO once per day "between courses"

14-day cycle for 4 cycles

References

1. Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. link to original article contains verified protocol PubMed content property of HemOnc.org
2. Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. Epub 2006 Oct 31. link to original article contains verified protocol PubMed
3. Abstract: Johannes Matschke, Hannes Müller-Beißenhirtz, Ilona Vester, Bernd Hertenstein, Lewin Eisele, Hildegard Lax, Claudia Ose, Ulrich Dührsen. A Randomized Trial Of Daily Prednisone Versus Pulsed Dexamethasone In Treatment Naïve Patients With Idiopathic Thrombocytopenic Purpura. Blood Nov 2013,122(21)325. link to abstract
4. Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. link to original article contains verified protocol PubMed

Dexamethasone & Eltrombopag

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Regimen

Study	Evidence
Gómez-Almaguer et al. 2014	Pilot, <20 pts reported

Therapy

• Dexamethasone (Decadron) 40 mg/day PO on days 1 to 4
• Eltrombopag (Promacta) 50 mg PO once per day on days 5 to 33

One course

References

1. Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC, Gómez-De León A, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, Tarín-Arzaga L, Hernández-Reyes J, Ruiz-Arguelles GJ. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014 Jun 19;123(25):3906-8. Epub 2014 May 6. link to original article contains verified protocol PubMed

Dexamethasone & Rituximab

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Regimen ("R+3Dex")

Study	Evidence
Imahiyerobo et al. 2013	Retrospective

Immunosuppressive therapy

• Dexamethasone (Decadron) 28 mg/m2/day (max dose of 40 mg) on days 1 to 4, repeated every 2 weeks for 3 cycles
• Rituximab (Rituxan) 375 mg/m² IV once per week on weeks 1 to 4

References

1. Abstract: Retrospective: Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. link to abstract

Intravenous immunoglobuin

Study	Evidence	Comparator	Efficacy
Godeau et al. 1999	Phase III	0.5g/kg IVIG	Higher response

Therapy

• Intravenous immunoglobulin (IVIG) 1gm/kg body weight on day 1

References

1. Bertrand Godeau, Marie-Therese Caulier, Laurent Decuypere, Christian Rose, Annette Schaeffer, and Philippe Bierling for the Groupe d'Etude du Traitement du PTAI. British Journal of Hematology. 1999; 107: 716-719. Link to article PubMed

Prednisone monotherapy

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Variant #1

Study	Evidence	Comparator	Efficacy
Wei et al. 2015	Phase III	Dexamethasone	Inferior CR rate

Immunosuppressive therapy

• Prednisone (Sterapred) as follows:
  • 1 mg/kg/day PO on days 1 to 28
  • Afterwards, tapered over 4 to 6 weeks with a goal of maintenance dosing less than 15 mg/day or "complete termination"
    • Taper schedule determined by treating physician

Variant #2

Study	Evidence	Comparator	Efficacy
Matschke et al. 2013	Phase III	Dexamethasone	Seems not superior

Immunosuppressive therapy

• Prednisone (Sterapred) as follows:
  • 1 mg/kg/day PO on days 1 to 14
  • Afterwards, tapered over 19 weeks with a goal of maintenance dosing less than 7.5 mg/day at the end of week 19

References

1. Abstract: Johannes Matschke, Hannes Müller-Beißenhirtz, Ilona Vester, Bernd Hertenstein, Lewin Eisele, Hildegard Lax, Claudia Ose, Ulrich Dührsen. A Randomized Trial Of Daily Prednisone Versus Pulsed Dexamethasone In Treatment Naïve Patients With Idiopathic Thrombocytopenic Purpura. Blood Nov 2013,122(21)325. link to abstract
2. Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. link to original article contains verified protocol PubMed

RhIG monotherapy

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RhIG: Rho(D) Immune Globulin

Variant #1, 25 mcg/kg

Study	Evidence
Bussel et al. 1991	Phase II

Eligibility: RhD-positive.

Therapy

• Rho(D) immune globulin (RhoGAM) 25 mcg/kg IV once on day 1, repeated as needed on days 3 & 4

One course

Variant #2, 50 mcg/kg

Study	Evidence	Comparator	Efficacy
Newman et al. 2001	Randomized Phase II, <20 pts (C)	Rho(D) 75 mcg/kg	Seems to have inferior platelet effect

Eligibility: RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 10⁹/L.

Therapy

• Rho(D) immune globulin (RhoGAM) 50 mcg/kg IV once

Supportive medications

• Acetaminophen (Tylenol) 650 mg PO once prior to therapy
• Prednisone (Sterapred) 20 mg PO once prior to therapy

Can be repeated if required to increase platelet count

Variant #3, 75 mcg/kg

Study	Evidence	Comparator	Efficacy
Newman et al. 2001	Randomized Phase II, <20 pts (E)	Rho(D) 50 mcg/kg	Seems to have superior platelet effect

Eligibility: RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 10⁹/L.

Therapy

• Rho(D) immune globulin (RhoGAM) 75 mcg/kg IV once

Supportive medications

• Acetaminophen (Tylenol) 650 mg PO once prior to therapy
• Prednisone (Sterapred) 20 mg PO once prior to therapy

Can be repeated if required to increase platelet count

References

1. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991 May 1;77(9):1884-93. link to original article contains verified protocol PubMed
2. Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/d of iv anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura. Br J Haematol. 2001 Mar;112(4):1076-8. link to original article contains verified protocol PubMed

TT4

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TT4: Triple Therapy (4?)

Regimen

Study	Evidence
Choi et al. 2015	Phase II

The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.

Immunosuppressive therapy

• Dexamethasone (Decadron) 40 mg/day PO on days 1 to 4
• Cyclosporine A 2.5 to 3 mg/kg/day on days 1 to 28
  • Dose adjusted for target trough of 200 to 400 mcg/L
• Rituximab (Rituxan) 100 mg IV once per day on days 7, 14, 21, 28

References

1. Choi PY, Roncolato F, Badoux X, Ramanathan S, Ho SJ, Chong BH. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4). Blood. 2015 Jul 23;126(4):500-3. Epub 2015 May 13. link to original article contains protocol link to PMC article PubMed

Relapsed or refractory

ATRA & Danazol

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Regimen

Study	Evidence	Comparator	Efficacy
Feng et al. 2017	Randomized Phase II	Danazol	Superior 12-month sustained response

Therapy

• All-trans retinoic acid (ATRA) 10 mg PO BID
• Danazol (Danocrine) 200 mg PO BID

16-week course

References

1. Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. link to original article contains protocol PubMed

Cyclosporine monotherapy

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Regimen

Study	Evidence
Emilia et al. 2002	Pilot, <20 pts

The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.

Immunosuppressive therapy

• Cyclosporine A as follows:
  • 5 mg/kg/day PO split into twice daily dosing for 6 days, then
  • 2.5 to 3 mg/kg/day with dose adjusted for target trough of 200 to 400 mcg/L

References

1. Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandini G, Ferrara L, D'Apollo N, Potenza L, Bertesi M, Torelli G. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15;99(4):1482-5. link to original article contains verified protocol PubMed

Danazol monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Ahn et al. 1983	Pilot, >20 pts
Feng et al. 2017	Randomized Phase II	ATRA & Danazol	Inferior 12-month sustained response

Note: Ahn et al. 1983 gave a range of 200 mg PO from two to four times per day; the dose below is from Feng et al. 2017

Endocrine therapy

• Danazol (Danocrine) 200 mg PO BID

16-week course

References

1. Ahn YS, Harrington WJ, Simon SR, Mylvaganam R, Pall LM, So AG. Danazol for the treatment of idiopathic thrombocytopenic purpura. N Engl J Med. 1983 Jun 9;308(23):1396-9. link to original article contains verified protocol PubMed
2. Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. link to original article contains protocol PubMed

Dexamethasone monotherapy

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Regimen

Study	Evidence
Andersen et al. 1994	Pilot, <20 pts

Immunosuppressive therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

28-day cycles for 6 cycles

References

1. Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994 Jun 2;330(22):1560-4. link to original article contains verified protocol PubMed

Dexamethasone & Rituximab

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Regimen ("R+3Dex")

Study	Evidence
Imahiyerobo et al. 2013	Retrospective

Immunosuppressive therapy

• Dexamethasone (Decadron) 28 mg/m2/day (max dose of 40 mg) on days 1 to 4, repeated every 2 weeks for 3 cycles
• Rituximab (Rituxan) 375 mg/m² IV once per week on weeks 1 to 4

References

1. Abstract: Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. link to abstract

Eltrombopag monotherapy

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Variant #1

Study	Evidence	Comparator	Efficacy
Grainger et al. 2015 (PETIT2)	Phase III	Placebo	Superior durable platelet response

This regimen was intended for pediatric patients.

Growth factor therapy

• Eltrombopag (Promacta) with starting dose as follows:
  • Age 6 to 17, weighing at least 27kg, non-east Asian: 50 mg PO once per day
  • Age 6 to 17, weighing at least 27kg, east Asian: 25 mg PO once per day
  • Age 6 to 17, weighing less than 27kg, non-east Asian: 37.5 mg PO once per day
  • Age 6 to 17, weighing less than 27kg, east Asian: 25 mg PO once per day
  • Age 1 to 5, non-east Asian: 1.2 mg/kg/day oral suspension
  • Age 1 to 5, east Asian: 0.8 mg/kg/day oral suspension

Dose adjusted to a maximum of 75 mg/day, with temporary discontinuation for platelet count greater than 400 x 10⁹/L

Variant #2

Study	Evidence	Comparator	Efficacy
Bussel et al. 2009	Phase III	Placebo	Superior plt count of greater than or equal to 50 x 109/L on day 43

Growth factor therapy

• Eltrombopag (Promacta) 50 mg (starting dose) PO once per day

The dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 x 10⁹/L. Treatment was discontinued in patients who attained a platelet count greater than 200 x 10⁹/L

Variant #3

Study	Evidence	Comparator	Efficacy
Cheng et al. 2010 (RAISE)	Phase III	Placebo	Superior RR

Growth factor therapy

• Eltrombopag (Promacta) 50 mg PO once per day, with dose modifications:
  • Increase to 75 mg PO once per day allowed after day 22 for patients with platelet counts lower than 50 x 10⁹/L
  • Decrease to 25 mg PO once per day required for platelets counts between 200 and 400 x 10⁹/L
  • Drug was held for platelet count greater than 400 x 10⁹/L, until platelet count dropped below 150 x 10⁹/L

6-month course

Variant #4

Study	Evidence	Comparator	Efficacy
Bussel et al. 2007	Phase III	Placebo	Superior RR

Growth factor therapy

• Eltrombopag (Promacta) 50 mg PO once per day

Up to 6-week course

Variant #5

Study	Evidence
Saleh et al. 2012 (EXTEND)	Phase II

Growth factor therapy

• Eltrombopag (Promacta) 50 mg PO once per day, with adjustments:

Dose and schedule were individualized with the goal of achieving and maintaining platelets between 50 and 200 x 10⁹/L.

References

1. Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. link to original article PubMed
2. Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. link to original article contains verified protocol PubMed
3. RAISE: Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. link to original article contains verified protocol PubMed
4. EXTEND: Saleh MN, Bussel JB, Cheng G, Meyer O, Bailey CK, Arning M, Brainsky A; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-45. Epub 2012 Nov 20. link to original article contains verified protocol PubMed
5. PETIT2: Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. link to original article contains verified protocol PubMed
6. Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. link to original article PubMed

Fostamatinib monotherapy

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Regimen

Therapy

• Fostamatinib (Tavalisse) 100 mg PO twice per day
  • Dose may be increased to 150 mg PO twice per day after 4 weeks if needed to achieve platelet count of at least 50

References

1. James Bussel, Donald M. Arnold, Elliot Grossbard, Jiri Mayer, Jacek Trelinski, Wojciech Homenda, Andrzej Hellmann, Jerzy Windyga, Liliya Sivcheva, Alhossain A. Khalafallah, Francesco Zaja, Nichola Cooper, Vadim Markovtsov, Hany Zayed, Anne-Marie Duliege. Fostamatinib for the treatment of adjult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. American Journal of Hematology. 2018; 93:921-930. Link to original article. PubMed.
2. Fostamatinib (Tavalisse) package insert
3. Newland A, Lee EJ, McDonald V, Bussel JB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018 Jan;10(1):9-25. link to original article PubMed

Mycophenolate mofetil monotherapy

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Regimen

Study	Evidence
Taylor et al. 2015	Retrospective

Immunosuppressive therapy

• Mycophenolate mofetil (CellCept) 1 gm per day

References

1. Taylor A, Neave L, Solanki S, Westwood JP, Terrinonive I, McGuckin S, Kothari J, Cooper N, Stasi R, Scully M. Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol. 2015 Nov;171(4):625-30. Epub 2015 Aug 6. link to original article PubMed

Placebo

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Regimen

Study	Evidence	Comparator	Efficacy
Kuter et al. 2008	Phase III	Romiplostim	Inferior durable platelet response
Bussel et al. 2009	Phase III	Eltrombopag	Inferior RR
Cheng et al. 2010 (RAISE)	Phase III	Eltrombopag	Inferior RR
Ghanima et al. 2015 (RITP)	Phase III	Rituximab	Seems not superior
Grainger et al. 2015 (PETIT2)	Phase III	Eltrombopag	Inferior durable platelet response
Tarantino et al. 2016	Phase III	Romiplostim	Inferior durable platelet response

No active treatment; used as a comparator arm and here for reference purposes only.

References

1. Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article PubMed
2. Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. link to original article contains verified protocol PubMed
3. RAISE: Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. link to original article contains verified protocol PubMed
4. RITP: Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; on behalf of the RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4. link to original article contains protocol PubMed
5. Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. link to original article contains verified protocol PubMed
6. Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. link to original article contains verified protocol PubMed
7. Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. link to original article PubMed

Rituximab monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Godeau et al. 2008	Phase II
Ghanima et al. 2015 (RITP)	Phase III	Placebo	Seems not superior

Patients in Godeau et al. 2008 had "ITP lasting 6 or more months before inclusion; at least 1 previous treatment for ITP; and platelet count less than 30 × 10⁹/L at inclusion" and were candidates for splenectomy."

Immunosuppressive therapy

• Rituximab (Rituxan) 375 mg/m² IV once per week

Supportive medications

• (per Godeau et al. 2008):
• Patients received Streptococcus pneumoniae and Haemophilus influenzae vaccination at least 2 weeks before the first dose of Rituximab (Rituxan)
• Acetaminophen (Tylenol) 1 g prior to Rituximab (Rituxan)
• Methylprednisolone (Solumedrol) 60 mg IV prior to Rituximab (Rituxan)

4-week course

References

1. Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, Vekhoff A, Chauveheid MP, Stirnemann J, Galicier L, Bourgeois E, Haiat S, Varet B, Leporrier M, Papo T, Khellaf M, Michel M, Bierling P. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008 Aug 15;112(4):999-1004. link to original article contains verified protocol PubMed
2. Prospective cohort: Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, Kanter J, Neufeld E, Taube T, Ramenghi U, Shenoy S, Ward MJ, Mihatov N, Patel VL, Bierling P, Lesser M, Cooper N, Bussel JB. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012 Jun 21;119(25):5989-95. link to original article contains verified protocol link to PMC article PubMed
3. Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; on behalf of the RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4.link to original article contains protocol PubMed

Romiplostim monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Kuter et al. 2008	Phase III	Placebo	Superior durable platelet response
Tarantino et al. 2016	Phase III	Placebo	Superior durable platelet response

Patients in Kuter et al. 2008 were adults; some had undergone splenectomy. Patients in Tarantino et al. 2016 were less than 18 years old at time of study entry.

Growth factor therapy

• Romiplostim (Nplate) 1 mcg/kg SC once per week, with subsequent dose titration; see papers for details

References

1. Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article contains verified protocol PubMed
2. Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. link to original article contains verified protocol PubMed