What is the relationship between Ruxolitinib (Jakafi) and Polycythemia Vera?

From the Guidelines

Ruxolitinib is a highly effective treatment option for patients with polycythemia vera (PV) who are resistant or intolerant to hydroxyurea, as evidenced by the RESPONSE trial, which demonstrated significant improvements in symptom burden, hematocrit control, and spleen volume reduction 1.

Key Findings

• The RESPONSE trial showed that 49% of patients in the ruxolitinib group achieved a 50% or more reduction in their total symptom score (TSS) at 32 weeks, compared to 5% in the standard therapy group 1.
• Ruxolitinib also achieved hematocrit control in 60% of patients, compared to 20% in the standard therapy group, and a 35% or more spleen volume reduction in 38% of patients, compared to 1% in the standard therapy group 1.
• The European LeukemiaNet recommends ruxolitinib as a second-line therapy for PV patients who are intolerant or have an inadequate response to hydroxyurea, with a strong recommendation despite moderate confidence in the outcome measures 1.

Treatment Considerations

• The recommended starting dose of ruxolitinib is typically 10 mg twice daily, which can be adjusted based on patient response and tolerability, with a maximum dose of 25 mg twice daily.
• Treatment is usually continued long-term as PV is a chronic condition requiring ongoing management.
• Common side effects include anemia, thrombocytopenia, and increased risk of infections, so regular blood count monitoring is essential.
• Patients should also be aware that abrupt discontinuation can lead to symptom flare, so any dose adjustments should be done gradually under medical supervision.

Additional Recommendations

• Patients should maintain hydration, avoid extreme temperatures that may worsen pruritus, and continue regular follow-up appointments to monitor disease progression and treatment response.
• Ruxolitinib works by inhibiting JAK1 and JAK2 enzymes, which are crucial in the signaling pathways that drive excessive blood cell production in PV, helping to control symptoms such as splenomegaly, pruritus, and constitutional symptoms while reducing the need for phlebotomies.

From the Research

Relationship Between Ruxolitinib and Polycythemia Vera

The relationship between Ruxolitinib (Jakafi) and Polycythemia Vera is primarily focused on the treatment of the disease. Key points include:

• Ruxolitinib is approved for the treatment of patients with Polycythemia Vera who are intolerant or resistant to hydroxyurea 2, 3, 4.
• Studies have shown that ruxolitinib is effective in controlling haematocrit levels, reducing spleen volume, and improving symptoms and quality-of-life measures in patients with Polycythemia Vera 2, 5, 4.
• The efficacy and safety of ruxolitinib have been evaluated in several clinical trials, including the RESPONSE-2 trial, which compared ruxolitinib with best available therapy in patients with Polycythemia Vera without splenomegaly 2, 5.

Efficacy of Ruxolitinib

The efficacy of ruxolitinib in treating Polycythemia Vera is supported by several studies, including:

• The RESPONSE-2 trial, which found that haematocrit control was achieved in 62% of patients treated with ruxolitinib compared to 19% of patients who received best available therapy 2.
• The RuxoBEAT trial, which found that treatment with ruxolitinib in untreated Polycythemia Vera patients was feasible, well-tolerated, and efficient in reducing haematocrit levels and improving symptoms 6.
• A study published in 2021, which found that discontinuation of ruxolitinib in Polycythemia Vera patients was associated with generally favorable outcomes, although there is a lack of available salvage therapies 3.

Safety of Ruxolitinib

The safety of ruxolitinib in treating Polycythemia Vera has been evaluated in several studies, including:

• The RESPONSE-2 trial, which found that the most frequent haematological adverse events were anaemia and thrombocytopenia, although no cases of grade 3-4 anaemia or thrombocytopenia occurred with ruxolitinib 2.
• The RuxoBEAT trial, which found that treatment with ruxolitinib was well-tolerated, with no patients permanently discontinuing treatment due to adverse events 6.
• A review published in 2016, which summarized the safety profile of ruxolitinib and found that the most common non-haematologic adverse events were headache, diarrhea, pruritus, and fatigue 4.