How Do CSF1R Inhibitors Work?

Colony-stimulating factor 1 receptor (CSF1R) inhibitors also known as macrophage colony-stimulating factor receptors (M-CSFR) are a class of drugs used to treat tenosynovial giant cell tumors (TGCT; tumors in or around a joint that can cause pain and swelling and reduce movements) in adults associated with severe morbidity or functional limitations that is unlikely to be improved by surgery.

TGCT is a rare form of nonmalignant tumor that causes the synovium (thin layer of tissue or membrane that covers the inner surface of the joint) and tendon sheaths to thicken and overgrow, causing damage in the surrounding joint tissue characterized by signs and symptoms such as:

• Pain and swelling in the affected joint
• Stiffness in the joint
• Warmth or tenderness around the joint
• Locking, popping, or catching when moving the affected joint

The only content that belongs to this class is "pexidartinib," a selective inhibitor of a tyrosine kinase receptor called "CSF1R" (CSF1R pathway) with potential antineoplastic and immunomodulating activities.

CSF1R inhibitor binds to CSF1R expressed on monocytes, macrophages, and osteoclasts and inhibits the binding of CSF1R ligands and interleukin-34 to CSF1R which prevents CSF1R activation and CSF1R-mediated signaling in tumor cells. This binding helps to block the production of inflammatory mediators by macrophages and monocytes and thus helps in reducing inflammation.

CSF1R inhibitor is administered via oral route, typically twice daily on an empty stomach, at least one hour before or two hours after food.

CSF1R inhibitors work in the following ways:

• They belong to a class of medications called “kinase inhibitors” that work by slowing or stopping the growth of tumor cells.
• They work by inhibiting the activation and signaling of tumor-permissive cytokines and receptor tyrosine kinases that play a central role in tumor cell proliferation and survival.

CSF1R inhibitor is indicated for adults with TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

Some of the common side effects include:

• Nausea
• Vomiting
• Constipation
• Diarrhea
• Tiredness/weakness
• Loss of taste sensation
• Changes in hair color
• Decreased appetite
• Dry mouth

Other rare side effects include:

• Dizziness 
• Fatigue 
• Rash/itching
• Anemia (low red blood cell count)
• Shortness of breath
• Chills, sore throat, fever, or cough
• Thrombocytopenia (low blood platelet count)
• Hypophosphatemia (low blood phosphate level)
• Hypertension (high blood pressure)
• Swelling of the hands, feet, legs, or ankles
• Eye edema
• Blurred vision
• Liver disorders
• Alopecia (unpredictable, patchy hair loss)
• Increased liver enzymes

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of CSF1R inhibitors include:

• Pexidartinib
• Turalio