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What Are JAK Inhibitors and How Do They Help Treat Myelofibrosis?
Posted: Apr 01, 2024
What Are JAK Inhibitors and How Do They Help Treat Myelofibrosis? image

JAK inhibitors, also known as Janus kinase inhibitors, are a type of medication that works by targeting specific "messengers" inside your immune system. These messengers, called JAK proteins (JAK1, JAK2, JAK3, TYK2), help control how your immune system functions. By blocking the activity of these JAK proteins, JAK inhibitors can help regulate the immune system and potentially treat certain conditions.

Which JAK Inhibitors Are Approved for Myelofibrosis Patients?

The FDA has approved the use of JAK inhibitors for multiple diseases, including myelofibrosis, rheumatoid arthritis, polycythemia vera, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and graft-versus-host disease.

Ruxolitinib (Jakafi) is the most commonly used JAK inhibitor when treating myelofibrosis. However, while existing treatment options primarily manage symptoms, new therapies are showing promise in potentially altering the course of the disease. Next-generation JAK inhibitors target specific immune system pathways and aim to be more effective with potentially fewer side effects.

Newly FDA-approved JAK inhibitors, such as fedratinib (Inrebic), momelotinib (Ojjaara), and pacritinib (Vonjo), are now being prescribed for patients with myelofibrosis.

  • Fedratinib can be used for patients with over 50,000 platelets who have intermediate or high-risk disease
  • Momelotinib is approved for patients with intermediate or high-risk myelofibrosis and anemia
  • Pacritinib is for intermediate or high-risk myelofibrosis patients with less than 50,000 platelets

What Do We Know About the Benefits and Risks of New JAK Inhibitors?

Fedratinib, momelotinib, and pacritinib are all relatively new medications, and long-term data is still emerging. Clinical trials are ongoing to further evaluate the benefit and safety of these newer JAK inhibitors in myelofibrosis and other myeloproliferative neoplasms (MPNs). Here's a breakdown of some promising advantages:

  • Improved anemia management: Ruxolitinib can sometimes worsen anemia, a common complication in myelofibrosis. In clinical trials, pacritinib and momelotinib have shown promise in potentially improving or stabilizing hemoglobin levels, reducing the need for transfusions.
  • Reduced splenomegaly: Similar to ruxolitinib, these newer JAK inhibitors may help shrink an enlarged spleen (splenomegaly), a symptom that can cause discomfort and fatigue.
  • Targeted effects: These newer JAK inhibitors might have a more specific targeting profile compared to ruxolitinib, potentially leading to fewer side effects. More research is needed to confirm this benefit. 
  • Can be combined with other agents: Investigators are exploring new ways to optimize JAK inhibitor's potency by combining them with other targeted therapies for patients who no longer respond to JAK inhibition.

In addition, each of these agents can be particularly beneficial for specific myelofibrosis patients, for example: 

  • Pacritinib can be used regardless of platelet counts, even in patients with very low platelet levels (severe thrombocytopenia)
  • Momelotinib and pacritinib are useful in patients with anemia, particularly transfusion-dependent anemia
  • Fedratinib can be used in the first-line treatment, but it can be a good second-line option for patients who are ruxolitinib-resistant

What About the Side Effects of JAK Inhibitors?

While new JAK inhibitors offer promising benefits for myelofibrosis treatment, it's important to be aware of potential side effects. Some of the most common ones are:

  • Increased risk of infections: JAK inhibitors can suppress the immune system, making you more susceptible to infections. Practicing good hygiene and maintaining open communication with your doctor are crucial.
  • Blood cell count changes: These medications may affect your blood counts, including a decrease in white blood cells (neutropenia) or platelets (thrombocytopenia). Regular blood tests are necessary to monitor these counts. 
  • High blood pressure (hypertension): Some patients may experience an increase in blood pressure. Your doctor will monitor your blood pressure and adjust medications if needed. 
  • Gastrointestinal issues: Nausea, vomiting, diarrhea, or constipation are possible side effects. Dietary adjustments and medications can often help manage these. 

Fedratinib may interfere with the body's ability to absorb thiamine (vitamin B1), increasing the risk of Wernicke encephalopathy, a serious brain condition caused by thiamine deficiency. Symptoms can include confusion, vision problems, and unsteady walking.

Expanding the Therapeutic Options for Myelofibrosis Patients

Every case of myelofibrosis is different. Because of this, doctors need to tailor treatment plans to each patient's specific symptoms and genetic makeup. Ideally, we'd have treatments that stop the disease from getting worse and prevent serious complications like bone marrow failure or leukemia. While most therapeutic options primarily manage symptoms, newer JAK inhibitors show promise in potentially altering the course of the disease. 

Myelofibrosis research is moving fast, and there is hope for even better treatments in the future! Stay up-to-date with HealthTree for Myelofibrosis by creating your free account. 

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Sources: 

The author Lisa Foster

about the author
Lisa Foster

Lisa Foster is a mom of 3 daughters, a puzzle lover, writer and HealthTree advocate. She believes in the mission of the foundation and the team that builds it forward. She calls Houston, Texas home. 

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