Jakafi (ruxolitinib) is a potent and selective inhibitor of Janus-associated kinases JAK1 and JAK2. By inhibiting these enzymes, it blocks signaling pathways driven by cytokines and growth factors, thereby reducing pathological blood cell proliferation and inflammation.

Indications:

• Myelofibrosis (MF): Intermediate or high-risk primary MF, post‑PV MF, or post‑essential thrombocythemia MF. Approved in 2011 in the U.S.

• Polycythemia Vera (PV): For patients intolerant of or with inadequate response to hydroxyurea. Approved in 2014. 

• Graft‑Versus‑Host Disease (GVHD):

  • Acute steroid-refractory GVHD, age ≥ 12: Approved May 2019.

  • Chronic GVHD after 1–2 other systemic therapies: Expanded indication in 2021.

Clinical Benefits:

• MF trials (COMFORT-I/II) showed significant spleen volume reduction and symptom relief (e.g., 35% spleen reduction in 28.5% of patients at 48 weeks vs 0% with standard care).

• RESPONSE trial in PV: better hematocrit control and spleen reduction than conventional therapy.

• GVHD studies demonstrated ~50–70% overall response rates in refractory acute and chronic cases.

Side Effects & Precautions:

• Common adverse events: Anemia, thrombocytopenia, neutropenia, bruising, dizziness, headache, diarrhea, weight gain, fluid retention, elevated cholesterol, and liver enzymes

• Infection risk: Including serious infections, herpes zoster, and fungal infections; monitor closely.

• Skin cancer risk: Non‑melanoma skin cancers have occurred; periodic skin exams advised.

• Cardiovascular alerts: Possible increased risk of heart attack, stroke, or death in patients with cardiovascular risk factors or smokers.

• Drug interactions: Metabolised mainly by liver enzyme CYP3A4, requiring caution when co-administered with strong inhibitors or inducers. Dose adjustments recommended.

• Special considerations: Avoid during pregnancy and breastfeeding. Monitor for rare CNS infections (e.g. PML) and reactivation of hepatitis B.

  
  Pharmacokinetics:

• Highly bioavailable (~95%), with a short elimination half-life (approx. 2.8–5.8 hours for parent plus metabolites). Primarily excreted via urine (~74%) and feces (~22%).

In summary:
Jakafi is a cornerstone therapy for serious myeloproliferative disorders and refractory GVHD. It works by targeting JAK1/2 to control abnormal blood cell production and inflammatory signaling. While highly effective—improving symptoms, spleen size, and hematocrit—it requires vigilant monitoring due to common blood cell suppression, infection risk, skin cancer, and metabolic effects.

Let me know if you'd like a breakdown of dose adjustment protocols, results from specific trials, or patient-reported experiences!