Ruxolitinib (Jakafi)

Approved for intermediate or high risk myelofibrosis-including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.

A selective Janus kinase (JAK) 1 and 2 inhibitor.

It inhibits both JAK1 and JAK2.

Ruxolinitinib has anti-proliferative effects, lowers counts of white blood cells, platelets, and red blood cells, and reduces the size of the spleen and liver.

It is also anti-inflammatory based on combined inhibition of JAK1 and JK2.

It decreases the cytokines in the body that cause inflammation and contribute to the characteristics of myelofibrosis disease biology and associated symptoms.

It explains why patients with melofibrosis the weight loss, impaired ability to walk, fatigue, weakness, night sweats, and bone aches all resolve to a significant degree during treatment with  ruxolitinib.

Approved for treatment of patients with polycythemia vera who are intolerant to hydroxyurea.

Associated with thrombocytopenia, anemia, and neutropenia.

Ruxolitinib is well tolerated with anemia and thrombocytopenia the most frequent adverse events.

Associated with bruising, dizziness and headache, fatugue, dyspnea, diarrhea and nausea.

Fatigue is the most common reported severe symptom.

Thrombocytopenia more likely to occur in patients with a platelet count of 200,000 or less at the time of the initiation of therapy.

Associated thrombocytopenia is generally reversible and managed by reducing the dose, or temporarily withholding the agent.

Neutropenia is generally reversible.

Dose modifications recommended with strong CYP3A4 inhibitors, or with renal or hepatic insufficiency.

In 2 trials of 528 patients with resistant or refractory disease, or any eligible for bone marrow transplantation, with all patients having splenomegaly, patients receiving ruxolitinib (Jakafi) experienced greater than 35% reduction in spleen size, and a greater than 50% reduction in myelofibrosis symptoms compared with patients receiving placebo on best available care.

COMFORT-1 and COMFORT-2 trials demonstrated that this agent, when used in intermediate-2 or high risk myelofibrosis, reduces spleen size, improves myelofibrosis related symptoms burden and improves overall survival.

Ruxolitinib has been approved for the treatment of intermediate and high-risk myelofibrosis.

Ruxolitinib selectively inhibits the proliferation of JAK2 V617F-driven Ba/F3 cells, and is correlated with decreased levels of phosphorylated JAK2 and of signal transducer and activator of transcription 5 (STAT 5) (Quintas-Cardama A et al).

Ruxolitinib in myelofibrosis associated with weight gain, reduction in spleen size and in debilitating symptoms.

Ruxolitinib controls symptoms by mediating suppression of inflammation, mirrored by a reduction in pro-inflammatory and pro angiogenic cytokines.

With Ruxolitinib reduction in cytokines is paralleled by significant shrinkage of the spleen.

Ruxolitinib response is independent of JAK2 mutational status.

Ruxolitinib starting dose is 20 mg twice a day for patients with platelet count above 200,000, and for patients with platelets between 100,00-200,000 is 15 mg twice a day with those platelets between 50 and 100,000 5 mg twice a day.

Ruxolitinib requires close monitoring and titrate dose based on platelet count over the first 3-6 months.

Ruxolitinib is not recommended for patients with platelet count below 50,000.

Approved for management of polycythemia vera only in patients who have failed prior therapy, or who are intolerant to hydroxyurea.

RESPONSE trial established the efficacy and safety of Ruxolitinib vs best supportive therapy in patient resistant or intolerant of hydroxyurea with polycythemia vera.

Ruxolitinib is front-line therapy for patients with polycythemia Rubra Vera who developed myelofibrosis, reducing by 30% the risk of death compared to a control arm.

Ruxolitinib Combo Therapy Reduces Symptom Burden in Patients With PV, MF

Results from a study of patients with polycythemia vera (PV) and myelofibrosis (MF) showed that ruxolitinib therapy plus low-dose pegylated interferon-α2 (PEG-IFNα2) improved cell counts and reduced symptom burden with acceptable toxicity.

2-year clinical trial to evaluate the use of combination ruxolitinib and low-dose PEG-IFNα2 in 32 patients with PV and 18 with primary- or secondary MF.

Overall, 31%patients with PV achieved remission, including 9% who achieved complete remission, and 44% patients with MF achieved remission, including 28% who achieved complete remission.

Patients with PV and MF had a cumulative incidence of peripheral blood count remission of 0.85 and 0.75, respectively.

Findings also demonstrated a decrease in median JAK2 V617F allele burden from 47% to 12%, with 41% of patients achieving a molecular response.

Combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with [PV or MF].

No well-defined criteria is available for ruxolitinib failure.
Median survival is 14-18 months and patient with sub optimal a loss of spleen response.

Sub optimal response or loss of response to splenomegaly is one feature of ruxolitinib failure.

The FDA has approved ruxolitinib (Jakafi) for the treatment of adult and pediatric patients ≥12 years of age with steroid-refractory acute graft-versus-host disease (aGVHD).

It has limited anti-clonal activity, associated dose limiting cytopenias, infectious complications, non-curative nature, and substantial rates of discontinuation.
Some patients experience weight gain.

In all reasonably fit patients in the transplantation age with suitable donors should be considered for hematopoietic  stem cell transplantation in patients unresponsive or failures to ruxotinib.

THe approval is based on findings from the phase II REACH1 trial, which demonstrated that the combination of ruxolitinib with corticosteroids elicited a 57% overall response rate (ORR) at day 28 in patients with steroid-refractory aGVHD, with a complete response (CR) rate of 31%.

Ruxolitinib was administered at 5 mg twice daily, which could be increased to 10 mg twice daily if no cytopenias occurred.

Overall response rates were 82.6%, 41.2%, and 42.9%, among patients with grade 2, 3, and 4 GVHD, respectively.

About half of the people who develop acute GVHD do not respond adequately to steroids and may be benefitted by Ruxolitinib.


Ruxolitinib demonstrates improved overall response rates and failure-free survival compared with best available therapy in adolescent and adult patients with chronic graft-versus-host disease (REACH3 trial), in a population of patients with an inadequate response to steroids.


About half of patients with GVHD become refractory or addicted to systemic steroids, and no standard second-line therapy has been defined.


At week 24, overall response rates were 49.7% in the ruxolitinib group and 25.6% in the best available treatment group.


Median failure-free survival rates were not reached in the ruxolitinib group and was 5.7 months in the best available therapy group.


Discontinuation of the drug requires general tapering because sudden discontinuation causes withdrawal symptoms.

Treatment with ruxolitinib was not found to carry an increased risk of secondary malignancies in patients with polycythemia vera.

Chronic graft versus host disease is a multi system inflammatory disorder that occurs in approximately 40% of patients within the first year after allogeneic hematopoietic stem cell transplantation.

Ruxolitinib in the treatment of graft versus host disease following HSCT after the failure of one or two lines of systemic therapy resulted in a 64-70% response rate with complete response rate of 3 to 8% as a treatment option for adult and pediatric patients 12 years and older with chronic graft versus host disease.

The application of ruxolitinib cream resulted in greater re-pigmentation in vitiligo lesions than vehicle control through 52 weeks, but it is associated with acne and pruritus at the application site.










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