Q :: What treatments for ITP are available?
A:: There are many treatments for ITP. They all have different risks and benefits and some are very toxic. It is important to understand both the success rate and potential side effects before beginning a treatment. Hematologists may use several treatments at once to increase their success rate.
Treatments include (in alphabetical order) anti-D (WinRho SDF®), azathioprine (Imuran®), corticosteroids (ex. prednisone), cyclophosphamide (Cytoxan®), cyclosporine (Sandimmune®), danazol (Danocrine®), eltrombopag (Promacta®), gamma globulin (ex. IVIg), mycophenolate mofetil (Cellcept®), rituximab (Rituxan®), romiplostim (Nplate®), splenectomy, and vinca alkaloids (ex., Vincristine®). Additional treatments are in clinical trials. Some patients report success with complementary therapies such as vitamins, supplements, diet changes, herbs and energy work.
Q:: Are there ITP treatment guidelines?
A:: ITP treatments vary with the severity of the disease, age of the patient, the experience of the hematologist and other factors. Both the American Society for Hematology (ASH) and the British Society for Haematology (BSH) have published guidelines for treating ITP. A report “International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia” was published in December 2009 in the journal Blood. Seven of PDSA’s Medical Advisors and PDSA Founder Joan Young contributed to this report. ITP treatment is evolving as researchers learn more about the disease.
Q:: Is there one treatment that is usually recommended?
A:: An initial course of prednisone (a corticosteroid) is often given to newly diagnosed patients. Prednisone suppresses the immune system. It is hoped that suppressing the immune system will cause the patient’s platelet count to increase and remain elevated after the patient stops taking prednisone. Sometimes a short course of dexamethasone, another corticosteroid, is used instead of prednisone.
Q :: What are the side effects of these treatments?
A:: Side effects have been reported for each of the drugs used to treat ITP. However, side effects will vary from one person to another. Patients may experience all, some, or no side effects at all. Side effects for frequently used first-line treatments are described below.
Prednisone — Prednisone is a synthetic medicine (i.e., steroid) similar to cortisone, a natural substance produced in the body’s adrenal glands.
Possible side effects: Prednisone is generally only given for a few weeks at a time because it can have serious side effects with long-term use. And even when it is given for a short time, patients may become more irritable, have stomach upsets, sleep disturbances, increased appetite, weight gain, puffy cheeks, frequent urination, sugar in the urine, loss of bone density, or acne. When the medicine is stopped, most side effects will begin to disappear.
Intravenous gamma globulin (IVIg) — IVIg is a liquid concentrate of antibodies purified from the plasma (the liquid portion of the blood that doesn’t contain red blood cells) of healthy blood donors. IVIg is believed to work by overwhelming the spleen with antibody so that it cannot recognize the antibody-coated platelets. IVIg treatment will usually result in a rapid (24 to 48 hours) increase in the platelet count, but any improvement is generally short-lived. Treatment may be repeated until the platelet count improves. IVIg is delivered by an intravenous infusion directly into a vein in the arm for several hours a day over a period of 1 to 5 days.
Possible side effects: Some patients treated with IVIg experience nausea and vomiting, headaches or fever and rarely, aseptic meningitis, abnormal blood clots or kidney failure. Many patients are helped by pretreatment with acetaminophen and Benadryl®.
Anti-Rho(D) immune globulin (WinRho®) — WinRho is also a liquid concentrate of antibodies derived from healthy human plasma. However, this medicine is targeted against the Rh factor* on red blood cells. It is thought that WinRho binds to red blood cells to such an extent that the spleen is fully occupied eliminating red blood cells and does not have much opportunity to remove the antibody-coated platelets. Like IVIg, the response is usually rapid but temporary. If a hematologist recommends treating with WinRho, it will be given by intravenous infusion. The procedure takes less than a half hour and can be done during an outpatient visit. WinRho will generally not work if a patent is Rh-negative or has had a splenectomy (removal of the spleen).
Possible side effects: Temporary side effects from WinRho include fever, headache, chills, nausea and vomiting, anemia, and rarely, kidney failure. In 2009 the FDA revised the WinRho package insert to warn about rare cases of intravascular hemolysis (red cell destruction) experienced by a small number of patients who received WinRho.
Other treatments —You can contact our organization or visit our Web site (www.pdsa.org) for information about these.
Q:: If ‘front line’ therapies are not effective, what are the ‘second-line’ medical treatments that the doctor is most likely to use to raise platelet counts?
A:: If corticosteroids, IVIg, and anti-D treatments are not effective in raising platelet counts to a safe level or the side effects pose problems, several ‘second line’ treatments may be tried. The two primary ‘second-line’ treatments are either medical (drugs) or surgical (spleen removal). These second line treatments include the drugs danazol, dapsone, monoclonal antibodies (e.g., rituximab), and immunosuppressant drugs; surgery to remove the spleen (splenectomy); and the FDA-approved thrombopoietin mimetics or platelet growth factors.
Q:: What are the side effects of the most common second-line treatments?
A:: Side effects for the most common second-line treatments include the following:
B-cell depletion – B-cell depletion (anti-CD20) by a monoclonal antibody has not been approved by the FDA to treat ITP, although it has become a widely used treatment choice. Rituximab (Rituxan®) is one type of monoclonal antibody that was approved by the FDA to treat lymphoma. There has been some success in its use to treat ITP. Clinical studies are in progress.
Mechanism of action: Rituximab reduces the number of B cells in the body. B cells are a type of white blood cell that, when activated, multiply and produce antibodies. Since Rituxan reduces the number of B cells, it also reduces the number of cells that produce antibodies, including the antibodies that attack platelets, thereby enabling the platelet count to rise. Most recent reports from studies in the U.S. on the effects of Rituxan® showed that after being given to patients for four weeks, 32% of patients had an increase in platelets lasting up to a year.
Possible Side Effects: Side effects of Rituxan were reported in 87% of patients. Ten percent of patients reported very serious adverse effects that included fever, chills, weakness, nausea and headaches. Some hypersensitive patients may get serum sickness. Some rare cases of progressive multifocal leukoencephalophathy due to a specific virus have been reported to the FDA.
Immunosuppressants – Immunosuppressants are a class of drugs that are capable of inhibiting the body’s immune system. Many of the agents in this category are also cytotoxic (cell poisons) and are used in the treatment of cancer. Chemotherapy medicines have their greatest effect against rapidly dividing cells and, therefore, can be beneficial in the treatment of ITP by suppressing the cells involved in the hyperactive immune response. Immunosuppressants have been used as an almost last resort for patients with chronic ITP. Vincristine® and Cytoxan® (cyclophosphamide) are those most frequently prescribed. Imuran® (azathioprine) is used less frequently.
Possible Side Effects: Each of these drugs has a slightly different profile of side effects. These effects include hair loss, decreased immunity, gastrointestinal symptoms, bleeding from the bladder, damage to the central and peripheral nervous systems, bone marrow suppression, liver toxicity, and risk of developing leukemia.
Splenectomy – Another second-line treatment for ITP is surgery to remove the spleen (splenectomy) in patients whose platelet count remains below 30,000 and who have serious bleeding. The spleen is a large blood filter which, for many people, removes antibody-coated platelets. Theoretically, if the spleen is removed, the platelets will remain in circulation. However, there are other ways the body removes platelets, so this treatment sometimes fails to have a lasting effect.
The decision as to whether to undergo a splenectomy is a complex issue that each patient must consider carefully depending on their personal medical situation and medical history. The issues are too complex to fully cover here. The medical community has considerable experience with splenectomy. It has been used on thousands of patients over the decades in countries throughout the world. It has a reasonable cure rate and benefit to risk ratio.
Possible Side Effects: Short-term complications of splenectomy immediately following surgery may include infection, incisional bleeding, deep vein blood clots, pneumonia, incisional hernia, pancreas inflammation, and pulmonary embolism (blood clot that travels to the lungs). While general anesthesia prevents pain during the surgery, there may be incisional pain for several days after surgery. The spleen filters your blood and produces antibodies to help fight infections. After the spleen is removed you are not able to readily fight infections.
Platelet growth factors – Platelet growth factors are the newest approved form of treatment for patients with chronic ITP. Nplate® / romiplostim was approved in August 2008 by the U.S. Food and Drug Administration (FDA) as a chronic ITP treatment for splenectomized and nonsplenectomized patients that have had an insufficient response to either steroids, immunoglobulins, or splenectomy. Another platelet growth factor, PROMACTA® / Eltrombopag , received FDA approval in November 2008 for use in chronic ITP. These treatments can be effective options for raising platelet counts in ITP patients.
Mechanism of Action: Most previous treatments for ITP have focused on stopping destruction of platelets in the spleen and elsewhere. The platelet growth factors (also called “platelet producers” or thrombopoietin (TPO) receptor agonists) are a new class of treatments that stimulate platelet production. TPO, a protein made in the liver, naturally stimulates platelet production by the bone marrow. TPO receptor agonists bind to the same receptor as the TPO produced in the body and stimulate the bone marrow to produce more platelets.
While ITP is often considered a disease characterized by platelet destruction, recent research has shown that many people with ITP also have inappropriately low platelet production. The bone marrow stimulation prompted by the TPO receptor agonists (e.g., Nplate® or PROMACTA®) creates a sufficient number of additional platelets to overcome the platelet production defect in most people who receive these treatments. The result is a safe level of platelets with minimal side effects.
Nplate® / romiplostim – Recent studies of romiplostim indicated an overall response rate of 79% in splenectomized patients, and 88% in nonsplenectomized patients, with 0% and 14% response rates in the respective placebo groups. Nplate® is a weekly injection. The initial dose is 1 mcg/Kg/week with weekly doses escalated to increase the platelet count to ≥50,000. The dose is reduced or discontinued if the platelet count rises too high or the patient doesn’t respond.
Possible Side Effects: The most commonly reported side effect of romiplostim was headaches (35% in those taking romiplostim, 32% in those taking the placebo). Other reported side effects included dizziness, insomnia, pain in arms or legs, abdominal pain, shoulder pain, indigestion, and paresthesia (feeling of pins and needles in hands and feet). Potential serious adverse events included bone marrow reticulin deposition and worsening thrombocytopenia after discontinuation of romiplostim therapy. Other risks include blood clots from excessive platelet formation and potential for increased bone marrow blasts in patients with myelodysplasia.
For questions regarding the Nplate® patient assistance program , visit their Web site at https://www.amgenfirststep.com/ProductNplate.php or see the PDSA publication with information on patient healthcare assistance: http://www.pdsa.org/products-a-publications/free-materials.html
PROMACTA ® / Eltrombopag -- In recent short-term clinical studies the response rate where patients achieved a platelet count higher than 50,000 six weeks after treatment was 59% for Eltrombopag-treated patients on the 50 mg dose and 16% for placebo-treated patients. In earlier studies, after six weeks of treatment, the response rate of 70% in those receiving the 50 mg dose and 81% in those receiving the 75 mg dose, compared with only 11% in those getting the placebo. After 15 days on the study, more than 80% of patients getting the 50 mg and 75 mg doses of Eltrombopag responded with platelet counts in the normal range of 150,000—400,000. Studies with Eltrombopag for 24 weeks have shown similar rates of response and reduction in bleeding events.
Possible Side Effects: PROMACTA ® is a pill taken once a day. The most common adverse event reported in short-term studies was headaches, in 8% and 11% of patients receiving Eltrombopag and placebo, respectively. Other common side effects occurring in at least 5% of Eltrombopag patients included nausea, common cold, diarrhea, and vomiting. Potential toxicities of Eltrombopag include development of reticulin in bone marrow, changes in liver function tests, and a drop in platelet count after stopping the drug. Other risks include blood clots from excessive platelet formation and potential for increased bone marrow blasts in patients with myelodysplasia.
PROMACTA® may cause hepatotoxicity (drug-induced liver damage). Patients receiving therapy with PROMACTA® must have regular monitoring of serum liver tests. Information on patient assistance for those taking PROMACTA is available on their Web site: http://www.caresbygsk.com/patients-caregivers.html#Patient
Information is also available in PDSA’s booklet on patient healthcare assistance at: http://www.pdsa.org/products-a-publications/free-materials.html
Q::Do alternative treatments work?
A:: Some people report success with herbs, supplements, energy work, diet changes and other alternative treatments. There are many reported cases of their success but few formal studies. Many of the alternative treatments attempt to correct the underlying problem rather than treat the symptoms of the disease. They tend to take a longer time to be effective and have fewer unwanted side effects. Like the more traditional treatments, the alternative treatments do not have the same results in all who try them. For additional information on complementary and alternative treatments, visit the PDSA Web site: http://www.pdsa.org/treatments/complementary.html