Expert Recommendations for ITP Management
Recent recommendations for the treatment of adult chronic ITP are now available from two distinguished panel reports published in Blood:
- The American Society of Hematology 2011 evidence-based guideline for immune thrombocytopenia (hereafter referred to as the 2011 ASH guideline) (4/2011)[17]
- International consensus report on the investigation and management of primary immune thrombocytopenia (hereafter referred to as the ICR) (1/2010)[10]
Recommendations come from two distinct groups of physician experts:
- 2011 ASH guidelines: Six authors, all with lack of conflicts, five with prior publications on ITP and its treatment, four with demonstrated expertise in systematic reviews and guideline development, and three with clinical expertise in management of ITP[17]
- ICR: 22 authors, all with recognized clinical and research expertise in ITP[10]
An evidence-based approach
Both publications provide recommendations for treatment of ITP based on assessment of evidence[10][17]; the 2011 ASH guidelines refer readers to the ICR for more extensive reviews of clinical data in some areas.[17]
In both publications, the methodologies included exhaustive literature searches to find available evidence. The 2011 ASH guideline and the ICR utilized different criteria for selecting supporting evidence and graded the evidence according to different scales.[10][17]
The dual mechanism of ITP
According to the 2011 ASH guideline and the ICR, evidence shows that ITP involves both increased platelet destruction and decreased platelet production.[10][17]
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Spontaneous improvement or late remission
Experts on both the 2011 ASH guideline and ICR consensus panels agree that spontaneous improvement or late remission of ITP may occur—from 6 to 12 months or even years after diagnosis.[10][17]
Managing ITP—the role of TPO-receptor agonists
Both the 2011 ASH guideline and ICR recommendations for first-line ITP treatment options include corticosteroids as well as anti-D and IVIG. Due to the risk of complications, it is recommended that corticosteroids, as initial therapy, should be used for 3 to 4 weeks and then tapered off.[10][17]
Both 2011 ASH and ICR panels concur that Nplate® has proven efficacy in patients with chronic ITP, and provide recommendations for TPO-receptor agonists, including Nplate®, as second-line ITP treatment options.[10][17] Both expert panels also concur that most adverse events have been generally mild for TPO-receptor agonists.[10][17]
According to the 2011 ASH panel[17]:
- “We recommend: Thrombopoietin receptor agonists for patients at risk of bleeding who relapse after splenectomy or who have a contraindication to splenectomy and who have failed at least one other therapy.”
- “We suggest: Thrombopoietin-receptor agonists may be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids or IVIg and who have not had splenectomy.”
- “Strong recommendations are usually indicated by the phrase ‘we recommend…’ and weak recommendations by the phrase ‘we suggest…’.”
According to the International ITP Consensus Report (ICR)[10]*:
- Nplate® is part of the ICR Grade A recommendation for the TPO-receptor agonist class as second-line treatment.
- The grade A recommendation is defined as a standard of evidence that requires at least one randomized, controlled trial as part of a body of literature of overall good quality and consistency.
- The graded rating system is not meant to imply comparison of safety or efficacy of the treatments, but rather to describe various levels of evidence.
*Amgen Ltd. was among the sponsors of the International ITP Consensus Report.
Click here to read more on the clinical profile of Nplate®, an FDA-approved TPO-receptor agonist.
The goal of therapy and when to treat
The ASH and ICR panels agree that the primary goal in ITP is to sustain a platelet count that prevents serious bleeding. The decision to treat should be based on platelet count (< 30 x 109/L, according to the ASH guideline) as well as other considerations, such as the following[10][17]:
- Severity of bleeding
- Risk factors for bleeding
- Activity level
- Possible treatment side effects
- Patient preferences
Both publications maintain that their recommendations are intended as guides only and should not supercede the physician’s judgment based on the patient’s specific needs and preferences.[10][17]
INDICATION
Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.
Important Safety Information
Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia
- In Nplate® clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
- Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.
Thrombotic/Thromboembolic Complications
- Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®. Nplate® should be used with caution in patients with ITP and chronic liver disease.
- To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
- Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®.
- In a clinical study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy. Clinical studies are in progress to assess the risk of bone marrow fibrosis and clinical consequences with cytopenias.
- If new or worsening morphological abnormalities or cytopenia(s) occur, consider a bone marrow biopsy to include staining for fibrosis.
Worsened Thrombocytopenia after Cessation of Nplate®
- In clinical studies of patients with chronic ITP who had Nplate® discontinued, four of 57 patients developed thrombocytopenia of greater severity than was present prior to Nplate® therapy. This worsened thrombocytopenia resolved within 14 days.
- Following discontinuation of Nplate®, obtain weekly CBCs, including platelet counts, for at least 2 weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.
Lack or Loss of Response to Nplate®
- Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
- To detect antibody formation, submit blood samples to Amgen (1-800-772-6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
- Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.
Laboratory Monitoring
- Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
- Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.
Adverse Reactions
- In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
- Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%) , Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
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