Pruritus In Primary Myelofibrosis: Treatment Attempts, Response and Outcomes

Pruritus, often aquagenic, is a common and disabling feature of myeloproliferative neoplasms. It's prevalence in both polycythemia vera and primary myelofibrosis (PMF) has been well documented. Historically, a number of medications have been used to treat pruritus in PMF, including hydroxyzine, anti-histamines, hydroxyurea, and selective serotonin re-uptake inhibitors (SSRI's). Recent clinical trials with JAK or mammalian target of rapamycin (mTOR) inhibitors in PMF have identified pruritus as one of the most treatment-responsive disease traits. However, there has not been a comprehensive study comparing treatments for pruritus, response rate, and time to response in a large cohort of patients with PMF.

1) Describe treatment strategies for pruritus in a large cohort of patients with PMF.

II) Compare effectiveness of different treatments used to alleviate pruritus in PMF.

The current study population was comprised of 88 patients taken from a larger primary cohort of patients seen at the Mayo Clinic, Rochester between the years 2000 and 2010 with biopsy proven diagnosis of PMF (n=566) who reported pruritus at any time during their care at Mayo Clinic. Patients with pruritus secondary to underlying skin disorder confirmed by Mayo Clinic Department of Dermatology were excluded from evaluation. Clinical records were reviewed and data relating to pruritus was collected in the following domains: treatment type, response rate, and time to response. Treatment was stratified into medication class, and mean response rate and time to response was calculated.

Eighty eight patients (16% of primary cohort) reported pruritus that was not attributable to an underlying skin disorder. Forty nine of these patients (56%) reported severe pruritus and required treatment. The most commonly used medications to treat pruritus were anti-histamines (n=30), anti-depressants (n=22), topical corticosteroids (n=19), topical non steroids (n=13), hydroxyzine (n=14), JAK inhibitors (n=13), and hydroxyurea (n=8). Other medications included thalidomides (n=6), pain relievers (n=6), prednisone (n=5), UVB phototherapy (n=3), alpha interferon (n=2), gabapentin (n=1), and imatinib (n=1).

Among the 49 patients who received treatment for pruritus, response to therapy was documented in 35 patients. Eight three percent of patients (n=29) reported resolution of pruritus; 17% (n=6) had no improvement. Highest response rates were observed in patients treated with a JAK inhibitors (92%), thalidomide (83%), or pain relievers (83%). More traditional therapies including hydroxyzine, anti-histamines, and anti-depressants were moderately effective at relieving pruritus (43%, 37%, and 32% response rates respectively). The average time to pruritus alleviation in the entire cohort was 2 months (range: 1 day-25 months). See table 1 for response rates and average time to response for all treatment modalities.

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Pruritus is a treatment responsive feature of PMF. Over 80% of patients with PMF and pruritus in our cohort experienced resolution of pruritus after treatment. JAK inhibitors had the highest response rates for alleviating pruritus. As further molecular correlates for pruritus and PMF are discovered, additional targeted treatments like JAK inhibitors will hopefully emerge.

No relevant conflicts of interest to declare.