Polycythemia Vera (PV) is a chronic blood cancer where the bone marrow produces too many red blood cells, and sometimes white blood cells and platelets. This overproduction can thicken the blood, increasing the risk of blood clots, heart attack, or stroke. Managing PV often involves medications to control blood cell counts and alleviate symptoms. Two treatment options for adults with PV are Besremi (ropeginterferon alfa-2b) and Hydroxyurea. This article compares these medications.
Mechanisms of Action
Hydroxyurea functions as a myelosuppressive agent. It works by inhibiting ribonucleotide reductase, an enzyme involved in DNA synthesis. By disrupting DNA production, hydroxyurea slows the rapid division of cells in the bone marrow, reducing the overproduction of blood cells in PV. This mechanism primarily focuses on controlling elevated blood counts and associated symptoms.
Besremi (ropeginterferon alfa-2b) is a long-acting form of interferon alfa-2b. Its mechanism involves binding to the interferon alfa receptor (IFNAR) on cells. This binding initiates a signaling pathway that ultimately leads to anti-proliferative effects, meaning it helps to slow down the growth of abnormal blood cells. Unlike hydroxyurea, Besremi is thought to target the abnormal stem cells in the bone marrow, aiming to reduce the burden of the JAK2 allele, a common genetic mutation in PV patients. This distinct approach suggests Besremi may offer a more direct impact on the underlying disease process.
Practical Treatment Differences
The administration methods of these two medications differ significantly, impacting patient experience. Hydroxyurea is an oral medication, typically taken as a capsule once daily. This oral route offers convenience for many patients, allowing them to manage their treatment at home.
In contrast, Besremi is administered as a subcutaneous injection. Initially, injections are typically given every two weeks, and after blood parameters stabilize, the frequency may be extended to monthly. Patients can often be instructed on how to self-administer these injections.
Both medications have associated side effects that require monitoring. Common side effects of hydroxyurea include gastrointestinal issues, skin problems (rashes or ulcers), and hair loss. A more serious side effect is bone marrow suppression, which can lead to low blood cell counts, increasing the risk of infection, anemia, or bleeding.
Besremi’s common side effects include flu-like symptoms, including tiredness, weakness, fever, chills, and muscle and joint pain. Other side effects include itching, sore throat, elevated liver enzymes, and neuropsychiatric effects like depression. Patients receiving Besremi should be monitored for these symptoms, and some may require treatment discontinuation if symptoms become severe.
Regular monitoring is a shared aspect of managing both treatments to ensure safety and effectiveness. For hydroxyurea, routine blood work monitors blood cell counts for myelosuppression, with initial checks every two weeks, then monthly. Patients should report any side effects promptly. For Besremi, close monitoring with periodic clinical and laboratory evaluations is recommended due to the potential for serious side effects, including neuropsychiatric, autoimmune, ischemic, and infectious disorders. This includes monitoring for changes in blood cell counts, kidney function, liver enzymes, and thyroid function.
Treatment Outcomes and Ongoing Management
Both hydroxyurea and Besremi aim to control blood counts in polycythemia vera, but they may differ in their long-term impact on the disease. Hydroxyurea is effective at reducing red blood cell, white blood cell, and platelet counts, and can also help decrease spleen size and phlebotomy requirements. It has been shown to reduce the risk of blood clots in patients with PV. However, hydroxyurea primarily acts as a cytoreductive therapy, controlling the number of blood cells, and has not been shown to modify the underlying disease process or consistently improve all symptoms.
Besremi has demonstrated efficacy in achieving complete hematologic response, which means normalizing blood counts without the need for phlebotomy. Studies have shown that a complete hematologic response was achieved in a significant proportion of patients treated with Besremi, with rates increasing with longer treatment duration. A notable difference is Besremi’s ability to reduce the JAK2 allele burden, a common genetic mutation in PV. This reduction in the JAK2 allele burden is considered a potential indicator of disease modification, suggesting that Besremi may address the root cause of the disease rather than just managing its symptoms.
Polycythemia vera carries risks of disease progression, such as transformation to myelofibrosis or acute leukemia. While hydroxyurea is effective in controlling blood counts, the debate continues regarding its long-term impact on the risk of leukemic transformation. Some studies suggest an increased risk of myelofibrosis and mortality with longer duration of hydroxyurea treatment, and leukemic transformation has been observed in some patients.
Besremi’s potential for disease modification through JAK2 allele burden reduction is a significant long-term consideration. A lower JAK2 allele burden correlates with reduced risks of thrombosis and disease progression to secondary myelofibrosis or leukemic transformation. Long-term follow-up studies indicate a higher probability of event-free survival (absence of death, thrombosis, or disease progression) with Besremi compared to hydroxyurea. Factors influencing treatment choice may include patient age, desire for disease modification, and how the treatment impacts daily life and potential side effects.