Treatment Options for Immune Thrombocytopenia in Adults

This article was primarily authored by Sonam Patel, PharmD and reviewed by Ayesha Khan, PharmD, BCPS. Dr. Patel obtained her PharmD from University of Illinois College of Pharmacy, and is currently a PGY1 Pharmacy Practice resident at Rush University Medical Center in Chicago, Illinois.

Immune thrombocytopenia (ITP) is an antibody-mediated process involving the destruction of platelets. Various treatment options are available for ITP, with each exhibiting different mechanisms of action, pharmacokinetics, and financial cost. The following article provides a brief overview of ITP and considerations for selected treatment options.

ITP is characterized by low platelets due to immunologic destruction and decreased platelet production in the absence of an identifiable cause.¹ It is often times a diagnosis of exclusion as there are no reliable lab tests to confirm the diagnosis. This immunologic process can be further classified into 2 sub-types: primary ITP and secondary ITP. Primary ITP is defined as a platelet count < 100 x 10⁹/L in the absence of a disorder that may cause low platelets. Secondary ITP on the other hand is associated with a disorder such as autoimmune diseases that may cause low platelets.^1,2

The goal of ITP treatment is to prevent severe bleeding, but initial decisions regarding which therapy to select can be difficult.¹ Choice of therapy depends on many different factors including:

· Agent toxicity/side effects

· Bleeding severity

· Desired rate of platelet increase

· Patient’s activity level

· Patient preference

While there is no evidence to support a minimum platelet count threshold that clinicians should use to decide if a patient should be treated for ITP, the American Society of Hematology guidelines suggest initiating treatment in newly diagnosed patients with a platelet count of < 30 X 10⁹/L.

First-line therapies for treatment of ITP include corticosteroids, intravenous immune globulin (IVIG), and anti-D. Second-line therapies include rituximab and thrombopoietin receptor agonists (e.g. eltrombopag and romiplostim). Onset of action of the various agents play an important role in treatment selection. Prednisone, which is expected to raise platelet count relatively quickly, is generally used first line in most patients. IVIG is commonly used in patients who either cannot tolerate or who do not respond adequately to steroid treatment. Romiplostim, a thrombopoietic growth factor administered subcutaneously, is an effective option for those refractory to steroids and IVIG. However, cost and reimbursement of this agent may limit its use. Table 1 below provides a summary of the available treatment options.

Table 1: ITP Treatment Options

Agent

Place in Therapy

Evidence Grade

Dose

Onset of Action

Side Effects

Prednisone

First Line

2B

1 mg/kg orally x 21 days then tapered off¹

2 hours

Insomnia, fluid retention, hypertension, wound healing impairment, increased blood glucose

Intravenous

Immune Globulin

First Line if corticosteroids are contraindicated

2B

1 g/kg IV x 1, can repeat if necessary¹

1 to 3 days

Infusion reactions, anaphylactic reactions, and nephrotoxicity

Anti-D

First Line if corticosteroids are contraindicated

2C

50 mcg/kg IV

1 to 2 days

Hemolysis

Rituximab

Second Line*

2C

375 mg/m² IV once weekly x 4 weeks^3,4,5 or 100 mg IV once weekly x 4 weeks⁶

7-56 days

Infusion reactions, progressive multifocal leukoencephalopathy, hepatitis B reactivation, mucocutaneous reactions

Eltrombopag

Second Line

1B**

2C***

50 mg orally once daily (adjust based on platelet counts after ³2 weeks after treatment initiation)

1-2 weeks

Hepatic decompensation

Romiplostim

Second Line

1B**

2C***

1 mcg/kg subcutaneously once weekly (adjust by 1 mcg/kg/week to achieve platelet count > 50,000/mm³)

4 to 9 days

Headache, arthralgia, dizziness

* = for patients who failed one line of therapy such as corticosteroids, IVIG, or splenectomy

** = for patients who relapse after splenectomy or who have a contraindication to splenectomy and who have failed at least one other therapy

*** = for patients who have failed one line of therapy such as corticosteroids or IVIG and have not had a splenectomy

Acknowledgements:

References:

1. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.

2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.

3. Arnold DM, Dentali F, Crowther MA, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25-33.

4. Godeau B, Porcher R, Fain O, et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008;112(4):999-1004.

5. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-86.

6. Zaja F, Vianelli N, Volpetti S, et al. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010;85(4):329-34.