The RESPONSE and RESPONSE-2 trials found that ruxolitinib, a Janus kinase 2 (JAK2) inhibitor, provided far better hematocrit control and was better tolerated than interferon in patients with HU resistance or intolerance, according to a study published in the Annals of Hematology. Prior use of interferon did not affect response to ruxolitinib.

Up to 90% of patients with polycythemia vera (PV) receive hydroxyurea as their first-line therapy, but nearly one-quarter of these patients become resistant or intolerant of the treatment and many others find the adverse effects significantly reduce their quality of life. Pegylated interferon, often used in patients with hydroxyurea (HU) intolerance or resistance, has similar complete hematologic response rates to hydroxyurea and has comparable issues with intolerance, resistance and adverse effects.

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Both RESPONSE studies randomized patients to receive either ruxolitinib or investigator-determined best available therapy. Previous analyses showed ruxolitinib outperformed pooled best available therapies; this analysis specifically focused the comparison to interferon in patients intolerant or resistant to hydroxyurea.

In total, 184 patients received ruxolitinib and 187 received interferon as best available therapy. Among those who received interferon, 19% achieved hematocrit control compared to 62% of those who received ruxolitinib. Patients on ruxolitinib also had greater reduction in spleen volume and phlebotomy requirements and better symptom control.

Patients who crossed over from interferon to ruxolitinib had comparable rates of response, 61%-67%. The crossover patients also showed an improvement in hematologic and spleen responses and reduction in phlebotomy procedures. After crossover, patients also experienced a reduction in the rate and incidence of common adverse events with the exception of infections.

The researchers found that that patients who received ruxolitinib as a second-line therapy experienced superior outcomes, regardless of the first-line therapy used. This differs from the results seen in other studies which have found that patients treated with interferon rapidly improved in terms of hematologic control and spleen size over time. The investigators suggested that the difference could be attributed to the more advanced stage of patients in the RESPONSE trials compared to other studies.