PDSA E-News: December 30, 2015

Learning More about Current ITP Treatments:

Rethinking Intravenous Immunoglobulin (IVIg) Optimal Doses – Less May be Sufficient

An interesting case control study was reported on by Dr. Zeping Zhou Sr. This study compared the effects of different dosages of intravenous immunoglobulin (IVIg) for treating immune thrombocytopenia (ITP). A total of 167 ITP patients (91 adults and 76 children) were followed for 3 years. They were divided into three subgroups according to the dosages of IVIg administered: group A (0.2g/kg/day), group B (0.3g/kg/day), group C (0.4g/kg/day).

The surprising result is that the therapeutic response in 91 adult patients did not differ significantly among the three groups of IVIg dosages. The response rate of IVIg treatment in the three adult groups was 97.1% for group A, 97.2% for group B, and 100% for group C. The mean time for raising platelets to 30,000/µL in group A was 2.5 days, in group B 3.2 days, and in group C 2.9 days. Similar results were shown in the children groups. The follow-up results showed no significant difference of clinical outcome between groups A, B and C.

The report concludes that low-dose IVIg treatment is as effective as a high-dose regimen without increasing the risk of developing the patients into chronic ITP conditions. This suggests that ITP patients could be treated more cost-effectively by lower than conventional dosages of IVIg. See (3480) “Lower Dosages of Intravenous Immunoglobulin (IVIg) in Treating Immune Thrombocytopenia with Long-Term Follow-up of Three Years.”

Outcomes of Referrals for Mild and Moderate Thrombocytopenia in Pediatric ITP patients

What if maybe the best treatment for mild and moderate thrombocytopenia is to watch and wait? Don’t stress these patients and their families by making a referral to a large pediatric hematologist oncologist center. Dr. Charles Schlappi conducted a retrospective chart review of 1,140 pediatric ITP patients (average age 9.2 years old) who were referred to a large pediatric hematology oncology program over a three-year period (2012-2014). Of these, 902 were for hematologic diagnoses. Of those 103 (11.4 %) were referred for thrombocytopenia. For the purposes of this study, ITP severity was defined by platelet count as: mild (100,000 – 149,000 /mL), moderate (50,000 – 99,000 /mL), severe (20,000 – 49,000 /mL), and very severe (< 20,000 /mL).

Dr. Schlappi concluded that mild and moderate thrombocytopenia does not often progress or require interventions. Pediatricians should evaluate for rheumatologic disorders in their initial work-up for mild to moderate thrombocytopenia as well as consider medication-induced thrombocytopenia. A safe and cost-effective approach to a patient with mild to moderate thrombocytopenia could be to observe repeat laboratory data (including ANA*) in lieu of any other co-morbid condition. Using this approach could save families time, money, effort, and emotional stress in making appointments at large referral institutions. See (41) “Outcomes of Referrals for Mild and Moderate Thrombocytopenia.”

Editor’s note: * An ANA test detects antinuclear antibodies (ANA) in your blood. Your immune system normally makes antibodies to help you fight infection. In contrast, antinuclear antibodies often attack your body's own tissues.

Understanding More about TPO Treatments

Tapering Eltrombopag in Patients with Chronic ITP

Dr James Bussel reported on a study that tapered the thrombopoietin receptor agonist (TPO-RA) eltrombopag in patients with chronic ITP. Multiple studies have shown effective and safe long-term use; toxicity appears tolerable with thromboembolism the most common serious adverse event. An important question is if there will be an indefinite long-term need for treatment with eltrombopag once initiated. The aim of this study was to taper eltrombopag in a single arm study to determine how many and which patients will be able to discontinue treatment over time.

The study concluded that a substantial fraction of patients with chronic ITP are able to successfully taper off eltrombopag; the exact number (somewhere between 10 and 20 of the 32 patients) depends upon the group still tapering. The tapering schedule selected is slow and requires regular monitoring and individualization/flexibility. Even if patients do not fully taper off eltrombopag, they may be able to substantially reduce their dose. Dr. Bussel speculated that tapering eltrombopag as outlined in his paper may reduce the toxicity and costs of long-term treatment without diminishing hemostatic efficacy. See (1054) “Tapering Eltrombopag in Patients with Chronic ITP: How Successful Is This and in Whom Does It Work?”

Anti-GP1b Antibodies Are Associated with a More Severe ITP

Now there's another good reason to know your anti-platelet antibody status. In the past, researchers found ITP patients are more likely to respond to the Thrombopoietin Receptor Agonists (TPO-RA) (e.g., Nplate® or Promacta®) if they don't have the anti-GP1b type of anti-platelet antibodies. This finding was also true for the patient's response to IVIg and steroids. So thank your lucky stars if you don’t have anti-GP1b antibodies. Ok, but what if you do have anti-GP1b antibodies? This study of 91 ITP patients by Dr. Karaev found that the presence of antibodies to glycoproteins (GP) IIb/IIIa (integrin αIIbβ3) and GPIb/IX, detected in the majority of ITP patients, may correspond to different responses to treatment, i.e., anti-GPIb is associated with more severe disease, and less response to intravenous immunoglobulins and steroids.

They concluded that patients with anti-GP antibodies respond less to TPO-RA; however, there is no difference in response to TPO-RA between patients having both anti-GPIb and anti-GPIIb/IIIa, unlike responses to other treatments such as steroids or immunoglobulins. TPO-RA could be a preferable treatment option in ITP patients having anti-GPIb. See (1048) “Effects of Anti-Glycoprotein Antibodies on Response of Immune Thrombocytopenia Patients to Thrombopoietin Receptor Agonists and on Megakaryocytes Viability.”

The Promise of Future ITP Treatments

PRTX-100

Dr. John Semple reported on a possible new future treatment for thrombocytopenia. It is a drug called PRTX-100, which is a highly purified formulation of Staphylococcal Protein A (SpA). Dr. Semple reported on the results of a study that used a well-established murine (mouse) model. Mice were treated biweekly with placebo, IVIg, or doses of PRTX-100, with platelet counts measured weekly. The results demonstrated that IVIg and PRTX-100 were effective in elevating platelet counts in a murine model of human ITP. The results also support the proof of principle that PRTX-100 may be beneficial in patients with ITP. See (1045) “Successful Treatment of Thrombocytopenia with Staphylococcal Protein A (PRTX-100) in a Murine Model of Immune Thrombocytopenia (ITP).”

Editor’s Note: PRTX-100 is an immunomodulatory protein known to modify aspects of the human immune system. PRTX-100 has the ability, at very low concentrations, to bind to human B-lymphocytes and macrophages and to modulate immune processes. Pre-clinical data indicate that PRTX-100 may have the potential to treat ITP by reducing the immune-mediated destruction of the platelets. The two most recently approved drugs used to treat ITP, Nplate® (romiplostin) and Promacta®/Revolade™ (eltrombopag) both increase the production of platelets but do not appear to affect the underlying platelet destruction process. The safety, tolerability and pharmacokinetics of PRTX-100 have been characterized in five clinical studies. It was recently granted Orphan Drug Designation in the U.S. and Europe for the treatment of ITP. In two Phase 1b clinical trials in adult patients with active Rheumatoid Arthritis (RA), PRTX-100 was generally safe and well tolerated at all dose levels. At certain higher doses, more patients showed improvement in measures of RA disease activity than did patients at the lower dose or placebo cohorts. PRTX-100 is given as a short intravenous infusion. An open label dose escalation study of PRTX-100 in Adults with Chronic ITP has recently started. For details go to http://clinicaltrials.gov and type in study identifier NCT02401061.

Improving Treatment for Children with ITP

Effect of Romiplostim on Health-Related Quality of Life in Children with ITP and Associated Burden in their Parents

Effect of Romiplostim on Health-Related Quality of Life in Children with ITP and Associated Burden in their Parents In a study of 62 children with ITP ages 3 to 17, the kids were enrolled and randomized to receive romiplostim (42 patients) and placebo (20 patients). An overall platelet response was achieved by 34 patients. A durable platelet response was achieved by 24 patients. The Kids’ ITP Tool (KIT) was used to assess Health-Related Quality of Life in the kids, and associated burden in the parents. As might be expected, changes in kids’ KIT scores by treatment group showed numerically greater and more often statistically significant improvements for the kids receiving romiplostim (vs. placebo), and for platelet responders (vs. non-responders). In a mixed effects repeated measures analysis, greater improvement from baseline to weeks 8, 16, and 25 on Parent KIT scores was found in the romiplostim group vs. placebo. No significant difference was found between groups for the Child KIT scores. Dr. Susan Mathias concluded that romiplostim treatment is associated with reduced parental burden (measured by Parent KIT score). See (37) "Effect of Romiplostim on Health-Related Quality of Life in Children with Immune Thrombocytopenia and Associated Burden in Their Parents: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study."

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