From the Guidelines
Ruxolitinib is generally considered the first-line treatment for myelofibrosis, while momelotinib and pacritinib may be preferred in specific situations, such as anemia or severe thrombocytopenia, respectively.
Key Differences and Similarities
The main differences between momelotinib, ruxolitinib, and pacritinib lie in their mechanisms of action, side effect profiles, and patient populations for which they are best suited.
- Ruxolitinib inhibits JAK1 and JAK2, reducing spleen size and improving symptoms in patients with myelofibrosis, with a typical starting dose of 15-20 mg twice daily 1.
- Momelotinib also inhibits JAK1 and JAK2, but has the added benefit of inhibiting ACVR1, which can improve anemia, making it a potential option for anemic patients, with a usual dose of 200 mg once daily 1.
- Pacritinib primarily inhibits JAK2 and IRAK1, and can be used in patients with severe thrombocytopenia, where other JAK inhibitors may be contraindicated, with a typical dose of 200 mg twice daily 1.
Choosing Between Medications
When choosing between these medications, consider the patient's specific symptoms, blood counts, and comorbidities.
- Ruxolitinib remains the standard first-line therapy, but momelotinib may be preferred in anemic patients, while pacritinib can be an option for those with very low platelet counts.
- Regular monitoring of blood counts and spleen size is essential with all of these medications.
Side Effects and Considerations
Each medication has its own set of side effects and considerations.
- Ruxolitinib can cause anemia and thrombocytopenia as side effects.
- Momelotinib tends to have milder hematologic side effects compared to ruxolitinib, but can cause peripheral neuropathy.
- Pacritinib has less myelosuppressive effects but can cause gastrointestinal side effects, and has been associated with serious adverse events such as intracranial hemorrhage and cardiac failure.
From the Research
Differences between Momelotinib, Ruxolitinib, and Pacritinib
- Momelotinib exhibits an erythropoietic effect, attributed to alleviation of ineffective erythropoiesis through inhibition of activin A receptor type-I (ACVR1), which is not seen in ruxolitinib or pacritinib 2.
- Ruxolitinib has a higher incidence of thrombocytopenia compared to momelotinib, making momelotinib a better option for patients with thrombocytopenia 3.
- Pacritinib is an alternative option for patients with severe thrombocytopenia or ruxolitinib-resistance/intolerance, whereas momelotinib is preferred as the first-line JAKi treatment of choice 2.
Similarities between Momelotinib, Ruxolitinib, and Pacritinib
- All three medications are Janus kinase 2 (JAK2) inhibitors, which are effective in reducing spleen size and alleviating symptoms in patients with myelofibrosis 2, 4.
- They all have a similar mechanism of action, attributed to their canonical JAK-STAT inhibitory mechanism of action 2.
- Momelotinib, ruxolitinib, and pacritinib are all used to treat myelofibrosis, with momelotinib being the most recent FDA approval in September 2023 5.
Treatment Preferences
- In transplant-ineligible or deferred patients, the order of treatment preference is based on specific symptoms and individual assessment of risk tolerance, with momelotinib being considered as the first-line JAKi treatment of choice 2.
- For second-line therapy, ruxolitinib is favored over fedratinib based on toxicity profile, while pacritinib provides an alternative option in the presence of severe thrombocytopenia or ruxolitinib-resistance/intolerance 2, 4.