Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

Figures & data

Table 1 Phase III Trials of TPO-RAs in ITP

Study	Patient Number (n)	Location	Study Population	Major Results (Compared with Placebo)
Bussel 2009^Citation108	Eltrombopag n=76	Worldwide (63 sites)	Adults with ITP for ≥6 months and a pretreatment Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
	Placebo n=38			Significantly less bleeding
			39% splenectomized
Cheng 2011^Citation68	Eltrombopag n=135	Worldwide (75 sites)	Adults with ITP for ≥6 months and a pretreatment Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
				Reduced use of concomitant ITP medications
	Placebo n=62
				Reduced need for rescue therapy
			36% splenectomized
Tomiyama 2012^Citation69	Eltrombopag n=15	Japan	Adults ≥20 years old with ITP for ≥6 months and a pretreatment Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
	Placebo n=8			Significantly less bleeding
				Lower doses of eltrombopag were effective in Japanese patients
			70% splenectomized
Yang 2014^Citation70	Eltrombopag n=104	China	Adults with ITP for ≥12 months and a pretreatment Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
	Placebo n=51
			16% splenectomized
Kuter 2008^Citation62	Romiplostim n=83	United States and Europe	Adults with ITP for ≥12 months and a screening mean Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
	Placebo n=42 (patients from two parallel studies)			Reduced use of concomitant ITP medications
			50% splenectomized
Kuter 2010^Citation63	Romiplostim n=157	North America, Europe, and Australia	Adults with ITP for ≥12 months and a pretreatment Plt <50 × 10^9/L	Significantly higher rate of platelet response^a
				Reduced use of concomitant ITP medications
			0% splenectomized
				Lower rate of treatment failure
	Standard of care n=77			Lower rate of splenectomy
				Significantly less bleeding and transfusions
				Significantly improved quality of life
Shirasugi 2011^Citation109	Romiplostim n=22	Japan	Adults ≥20 years old with ITP for ≥6 months and a screening Plt ≤30 × 10^9/L	Significantly higher rate of platelet response^a
	Placebo n=12			Reduced need for rescue therapy
			44% splenectomized
Jurczak 2018^Citation79	Avatrombopag n=32	Europe, Asia, and Australia	Adults with ITP for ≥12 months and a screening mean Plt <30 × 10^9/L	Significantly higher rate of platelet response^a
				Reduced use of concomitant ITP medications
	Placebo n=17		33% splenectomized

Notes: Each trial was a prospective, multicenter, randomized, placebo-controlled, double-blind study except Kuter et al. (2010) which was open label. Reproduced with permission from Al-Samkari and Kuter⁵⁹. ^aPlatelet response defined as a platelet count ≥50 × 10⁹/L at a given assessment on treatment with TPO-RA or placebo.

Abbreviations: ITP, immune thrombocytopenia; Plt, platelet count.

Table 2 Other Agents for Use in the Subsequent Treatment Setting in ITP

Agent	Mechanism	Time to Response	Response Rate	Response Durability	Major Adverse Effects	Comments
Azathioprine^Citation110	Prodrug of antimetabolite 6-mercaptopurine; steroid-sparing immunosuppressant	Delayed (weeks to months)	30%	Good	Bone marrow suppression	Thiopurine S-methyltransferase activity should be measured prior to initiation
					Infection
					Hepatotoxicity
						Accepted as safe in pregnancy
Cyclophosphamide^Citation111,Citation112	Prodrug of phosphoramide mustard metabolite; immunosuppressant	Delayed (weeks to months)	30–40%	Good	Bone marrow suppression	Low-dose oral cyclophosphamide typically used
					Hemorrhagic cystitis
					Infection
Cyclosporine^Citation113,Citation114	Calcineurin inhibitor immunosuppressant	Early (1–2 weeks)	30–40%	Moderate	Nephrotoxicity	Trough levels should be monitored
					Hypertension, Metabolic side-effects
Danazol^Citation115^–^Citation118	Attenuated androgenic steroid hormone with glucocorticoid receptor activity	Delayed (weeks to months)	30–40%	Good	Virilization	May be combined with azathioprine but evidence for this is poor
					Hepatotoxicity
					Weight gain
Dapsone^Citation119^–^Citation121	Antibiotic with immunomodulatory and anti-inflammatory properties	Delayed (weeks)	40–50%	Poor	Methemoglobinemia	Glucose-6-phosphate dehydrogenase activity should be measured prior to initiation
					Hemolysis
Mycophenolate mofetil^Citation122^–^Citation124	Prodrug of mycophenolic acid, a purine synthesis inhibitor causing immunosuppression	Delayed (weeks)	40–50%	Good	Diarrhea
					Bone marrow suppression
					Infection
Vinca alkaloids (vincristine, vinblastine)^Citation125^–^Citation128	Microtubule toxin chemotherapeutic agents causing potent immunosuppression	Rapid (within 1 week)	70%	Poor	Vesication at infusion site	Administered as multiple weekly intravenous infusions; can be used as a rescue therapy of last resort
					Neuropathy
					Constipation
					SIADH

Notes: These agents are commonly labeled “third-line” treatments, although they may be used earlier or later in the treatment of ITP depending on clinical circumstances (i.e. pregnancy) or availability of more expensive agents (such as TPO-RAs or rituximab). Reproduced with permission from Al-Samkari and Kuter.¹¹

Abbreviation: SIADH, syndrome of inappropriate antidiuretic hormone secretion.

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