What is the treatment for polycythemia vera using Besremi (ropeginterferon jelta)?

Treatment of Polycythemia Vera with Besremi (Ropeginterferon Alfa-2b)

Besremi (ropeginterferon alfa-2b) is FDA-approved for treating adults with polycythemia vera and represents the first interferon specifically approved for this indication, administered subcutaneously every 2 weeks. 1

FDA-Approved Indication and Administration

• Besremi is indicated for treatment of adults with polycythemia vera regardless of prior treatment history 1
• The medication is administered as a subcutaneous injection every 2 weeks using single-dose prefilled syringes 1
• Patients can self-administer after proper training on injection technique, storage, and preparation 1

Dosing Regimen

• Standard starting dose is 100 µg every 2 weeks 1
• For patients already receiving hydroxyurea, start at 50 µg every 2 weeks 1
• Dose titration up to 500 µg can be performed in 50 µg increments based on response and tolerability 2
• An alternative higher-dose regimen (250-350-500 µg) has shown efficacy in patients with hydroxyurea intolerance, achieving 71.4% complete hematological response at 52 weeks 2

Clinical Efficacy

• In low-risk polycythemia vera patients, ropeginterferon alfa-2b demonstrated superiority over phlebotomy alone, with 84% achieving treatment response (maintaining hematocrit <45% without progressive disease) compared to 60% with phlebotomy only 3
• The medication reduces JAK2V617F allele burden significantly, with mean reduction from 58.5% at baseline to 30.1% at 52 weeks 2
• Complete hematological response rates increase over time: 61.2% at 24 weeks, 69.4% at 36 weeks, and 71.4% at 52 weeks 2
• Drug survival probability after median 3.15 years was 59%, with 97% of patients maintaining response at 3 years 4
• Sixty percent of responders remained phlebotomy-free during long-term follow-up 4

Role in Treatment Algorithm

• Besremi should be preferred as first-line cytoreductive therapy in younger patients (<40 years) requiring cytoreduction, as it is non-leukemogenic unlike hydroxyurea 5, 6
• The medication is particularly appropriate for women of childbearing age and pregnant patients, as it represents a safer alternative to hydroxyurea 5, 6
• Besremi is indicated for patients with pruritus, as interferon-α effectively manages this symptom 5
• For high-risk patients (age ≥60 years and/or history of thrombosis), Besremi serves as an alternative to hydroxyurea as first-line cytoreductive therapy 7, 5

Critical Safety Warnings

Besremi carries a boxed warning for potentially fatal neuropsychiatric, autoimmune, ischemic, and infectious disorders 1, 8

Absolute Contraindications

• Severe mental health problems, especially severe depression, suicidal thoughts, or suicide attempts 1
• Serious or untreated autoimmune disease 1
• Serious allergic reaction to interferon products 1
• Uncontrolled high blood pressure, congestive heart failure, serious abnormal heart rhythm, narrowing of coronary arteries, certain types of angina, or recent stroke/heart attack 1
• Certain types of liver problems 1
• Organ transplant recipients taking immunosuppressive medicines 1

Serious Adverse Effects Requiring Immediate Action

• Mental health problems: irritability, restlessness, agitation, confusion, depression, suicidal thoughts, or aggressive behavior require immediate discontinuation and provider contact 1, 8
• Autoimmune problems: new or worsening thyroid problems, hyperglycemia, or type 1 diabetes 1
• Cardiac complications: cardiomyopathy, heart attack, atrial fibrillation, or decreased coronary blood flow 1
• Patients should be closely monitored for persistently severe or worsening signs of these adverse effects 8

Monitoring Requirements

• Regular blood tests are required to monitor polycythemia vera control and check for side effects 1
• Pregnancy testing should be performed before starting treatment in women of childbearing potential 1
• Healthcare providers should carefully monitor patients throughout treatment, particularly for mental health changes 1

Special Populations

• Pregnancy: Besremi may cause fetal harm or miscarriage; effective contraception is required during treatment and for 8 weeks after the final dose 1
• Breastfeeding: Not recommended during treatment and for 8 weeks after final dose 1
• Menstrual effects: May affect menstrual cycles and cause periods to stop 1

Common Pitfalls to Avoid

• Do not exceed 1 dose every 2 weeks without consulting the prescriber 1
• Never reuse single-dose prefilled syringes 1
• Do not discontinue low-dose aspirin therapy (which should continue alongside Besremi for thrombosis prevention) 5
• Avoid using Besremi in patients with the contraindications listed above, as this significantly increases risk of life-threatening complications 1
• For patients requiring more than 3 phlebotomies in the first 6 months post-diagnosis, consider earlier initiation or dose escalation of ropeginterferon, as high phlebotomy need predicts treatment failure 4

Advantages Over Traditional Therapies

• Ropeginterferon alfa-2b demonstrated long-term superiority in efficacy and safety compared to hydroxyurea in phase III trials (PROUD-PV and CONTINUATION-PV) 9
• Unlike hydroxyurea, ropeginterferon is non-leukemogenic, making it safer for long-term use in younger patients 5, 6
• Better tolerance profile compared to non-pegylated interferon formulations 9
• Induces molecular remission with reduction in JAK2V617F allele burden, not just hematological control 2