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JAK Inhibitors - Overview, Uses, and Side Effects

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JAK Inhibitors - Overview, Uses, and Side Effects

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JAK inhibitors are useful in treating autoimmune disorders and blood and bone marrow cancers. To learn more, read the article below.

Medically reviewed by

Dr. Vishal Patidar

Published At August 1, 2022
Reviewed AtMay 9, 2024


Janus kinase inhibitors, commonly known as JAK inhibitors, inhibit the activities of one or more enzymes of the Janus kinase family. Janus kinase is an enzyme involved in the process of cell growth, cell division, differentiation of the specialized cells, and programmed death. The JAK inhibitors slow down the progression of autoimmune conditions, and cancers.

What Are Janus Kinase Inhibitors?

Janus kinase inhibitors are small molecules that interrupt the JAK-STAT (signal transducer and activator of transcription) signal pathways that are involved in many immune-mediated and inflammatory diseases.

Drug Group:

Janus kinase inhibitors belong to the disease-modifying anti-rheumatic drugs (DMARDs), primarily used for treating rheumatoid arthritis. The FDA-approved Janus kinase inhibitors are available in pill form and can be used with or without Methotrexate, a type of immunosuppressant.

What Are the Uses of Janus Kinase Inhibitors?

Janus kinase inhibitors are useful in the treatment of autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, ulcerative arthritis, and many blood disorders like myelofibrosis, polycythemia vera, and graft-versus-host disease (GVHD). They are useful in treating blood and bone marrow cancers.

Topical Janus kinase inhibitors are often prescribed for several skin conditions, such as alopecia areata. It also helps to reduce the severity of eczema. Xeljanz, a Janus kinase inhibitor, may be used for treating Crohn's disease, vitiligo, and atopic dermatitis. Baricitinib, a Janus kinase inhibitor, has recently been approved for use as an emergency use authorization (EUA) in hospitalized COVID-19 patients.

How Do Janus Kinase (JAK) Inhibitors Work?

The Janus kinase is a family of four enzymes: JAK 1, JAK 2, JAK 3, and tyrosine kinase2 (TYK2). These are essential for cytokine signaling and are linked to cancer and inflammatory diseases. Janus kinase inhibitors interrupt the transmission of intracellular signals involved in cellular processes such as immune response, blood cell formation, and cell cycle.

The drug's small molecules enter the cell, alter its function, and block the messages from cytokines that promote inflammation. The Janus kinase inhibitors stop the activity of the Janus kinase enzymes and calm the overactive immune system. Janus kinase inhibitors are distributed between the red blood cells and plasma. 70 % of the drug is metabolized in the liver and 30 % in the kidneys. The elimination half-life is three hours, and the state of concentration is achieved in 24 to 48 hours.

How to Use Janus Kinase Inhibitors?

Janas kinase inhibitors are available in a 5 mg and an 11 mg extended-release pill. They can be taken once or twice a day, usually without food. The improvement in the symptoms can be seen within two weeks of oral administration. It may take up to six months to reach complete effectiveness.

What Is the Dosage of Janus Kinase Inhibitors?

Dosage of Janus Kinase Inhibitors

What Are the Side Effects of Janus Kinase Inhibitors?

The primary side effect of Janus kinase inhibitors is susceptibility to infections and causing common respiratory and nasal infections.

Common infections may include,

The signs and symptoms may include,

  • Nausea.
  • Abnormal blood count.
  • Indigestion.
  • Weight gain.
  • Headaches.
  • Increased cholesterol levels.
  • High blood pressure.
  • Increased blood creatinine.
  • Increased bowel perforation.
  • Abnormal liver function tests.
  • Decrease in kidney function.

It is important to ensure that the medication is working by getting periodic blood tests such as,

  • Lymphocyte count.
  • Neutrophil or platelet count.
  • Hemoglobin.
  • Lipid profile to check cholesterol levels.
  • Liver function tests.
  • Viral hepatitis.
  • Periodic monitoring of heart rate and blood pressure.
  • Skin tests.

What Are the Precautions and Warnings of Janus Kinase Inhibitors?

1) Allergy - The use of Janus kinase inhibitors must be avoided in patients who have had allergic reactions to any of the Janus kinase inhibitors.

2) Pregnancy and Breastfeeding - Janus kinase inhibitors are rated Category D for their teratogenic effects. Therapy with Janus kinase inhibitors is contraindicated in pregnancy and in women of child-bearing age as it may cause an increased risk of side effects to the fetus. It is recommended to stop breastfeeding while using these drugs, for 18 hours after the last dose.

3) Surgery - It is recommended to stop the use of Janus kinase inhibitors one week prior to surgery as it may increase the risk of infection.

4) Kidney or Liver Dysfunction - Janus kinase inhibitors are metabolized in the liver. Therapy of Janus kinase inhibitors in patients with impaired hepatic and renal should be avoided.

5) Elderly - Patients aged 65 and above show a higher risk of adverse events while taking Janus kinase therapy than younger patients and should be administered cautiously.

6) Alcohol - It is advised to limit alcohol intake while taking Janus kinase inhibitors.

7) Live Vaccines - Live vaccines should be avoided while taking Janus kinase inhibitors. Patients should be up-to-date with their vaccinations and immunization prior to initiating therapy with Janus kinase inhibitors.

What Are the Commonly Used Janus Kinase Inhibitors?

The Janus kinase is a family of four enzymes that include JAK 1, JAK 2, JAK 3, and tyrosine kinase2 (TYK2) which are essential for cytokine signaling and are linked to both cancer and inflammatory diseases.

Some of the commonly prescribed Janus kinase inhibitors include,

  • Tofacitinib - The Janus kinase inhibitor is widely used for alopecia universalis and rheumatoid arthritis.
  • Topical Tofacitinib and Ruxolitinib - It is used for the treatment of alopecia. Ruxolitinib 1% and 1.5 % creams can be used to reduce psoriasis lesion size.
  • Xeljanz - This Janus kinase inhibitor is approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylosis, and juvenile idiopathic arthritis.
  • Olumiant - The FDA-approved inhibitor carries a black box warning for cardiovascular issues, malignancy, and thrombosis. Olumiant is combined with antivirals to reduce infectivity, viral replication, and inflammation associated with COVID-19.
  • Jakafi - Jakafi is FDA-approved to treat myelofibrosis, polycythemia, and acute graft-versus-host disease. It acts by inhibiting JAK1 and JAK2.
  • Rinvoq - Rinvoq is approved for the treatment of severe rheumatoid arthritis, ulcerative colitis, atopic dermatitis, and psoriatic arthritis.
  • Cibinqo - The drug is available in 50 mg, 100 mg, and 200 mg tablets and is used for the treatment of refractory, atopic dermatitis.
  • Abrocitinib - These topical Janus kinase inhibitors help to improve eczema symptoms and reduce itchiness and inflammation.


Janus kinase inhibitors interrupt the signal transduction of multiple cytokine receptors and help in the treatment of various autoimmune disorders. The drug can be used orally or topically, unlike the biological agents that require administration by injection.

Frequently Asked Questions


Which Drugs Belong to JAK Inhibitors?

The following drugs are considered JAK inhibitors:


Do JAK Inhibitors Cause Any Side Effects?

Jak inhibitors may cause the following side effects:
It weakens the immune system and makes the body susceptible to infections.
Increased blood pressure.
Rises blood creatinine levels.
Abnormal count of blood cells.


Which Are Known as Natural JAK Inhibitors?

Brevilin A is considered a natural JAK (Janus kinase) inhibitor, and studies show that it can be used in individuals resistant to other JAK inhibitors. In addition, the natural JAK inhibitor is used in combination with other chemotherapeutic agents to improve the prognosis. Several reports also suggest that fruits like pomegranates, strawberries, blackberries, etc., also have the potential to inhibit JAK.


Can JAK Inhibitors Lead To Hair Loss?

Some researchers studied the relationship between using JAK inhibitors and hair loss. The results showed that individuals who were under JAK inhibitor therapy had severe hair loss. In addition, it accounts for 70 % of total hair loss. Therefore, it is better not to use them to treat alopecia (hair loss).


Can JAK Inhibitors Manage Ankylosing Spondylitis?

Ankylosing spondylitis is a severe condition affecting the spine, resulting in pain and inflammation. Previously, non-steroidal anti-inflammatory (NSAID) drugs were used in treating ankylosing spondylitis. However, alternative JAK inhibitors are known to reduce the symptoms caused by ankylosing spondylitis effectively.


Do JAK Inhibitors Treat Eczema?

JAK (Janus kinase) inhibitors treat several autoimmune disorders by decreasing the inflammation associated with the disease and its related symptoms. Therefore, JAK inhibitors are used for treating eczema, a skin disorder that causes dry and itchy skin.


Does Methotrexate Come Under JAK Inhibitors?

Methotrexate is an effective drug in treating autoimmune disorders, especially rheumatoid arthritis. In addition, its primary mechanism of action is to inhibit the JAK pathway. Compared to other JAK inhibitors, Methotrexate effectively reduces inflammation, suppresses immunity, and is affordable.


Can I Take JAK Inhibitors for Vitiligo?

Vitiligo is a condition that causes pale patches on the skin. The Food and Drug Administration (FDA) has authorized the use of JAK inhibitors in treating vitiligo, as it dramatically helps in repigmentation. In addition, drugs like Tofacitinib, Ruxolitinib, and Baricitinib are available as creams (topical application) for managing vitiligo.


Does Taking JAK Inhibitors Lead To Neuropathy?

Jak inhibitors have now been used for treating various autoimmune disorders, including rheumatoid arthritis. However, these drugs have different side effects, including headache, nausea, increased blood pressure, etc. Drugs like Tofacitinib and Ruxolitinib are commonly used to treat rheumatoid arthritis. However, studies show that the long-term use of Tofacitinib may eventually lead to the development of peripheral neuropathy.


How Long Does It Take for JAK Inhibitors to Cure Alopecia?

JAK inhibitors were involved in the study for the treatment of alopecia. However, it showed promising results in treating hair loss and increased hair growth. The complete regrowth of hair happened within six months of treatment. In addition, the follow-up study also showed that hair loss occurred again in those patients after the cessation of treatment within two to three months.


Can JAK Inhibitors Reduce Inflammation?

JAK inhibitors have anti-inflammatory properties and are therefore used in the management of rheumatoid arthritis. The M1 macrophages in our body are responsible for stimulating the immune response. However, the JAK inhibitors are responsible for modifying the activated state of M1 macrophages and suppressing the immune system, thereby reducing inflammation.


Are JAK Inhibitors Approved for Rheumatoid Arthritis?

Yes, the Food and Drug Administration (FDA) has accredited the use of JAK (Janus kinase) inhibitors for various disorders like alopecia, rheumatoid arthritis, etc. These drugs mainly act by modifying M1 macrophages and thereby reducing the inflammation caused by rheumatoid arthritis. Tofacitinib and Baricitinib are approved to be used in patients with rheumatoid arthritis.


Do JAK Inhibitors Weaken the Immune System?

Yes, the JAK inhibitors may weaken or suppress the immune system. In addition, specific cells responsible for immune response are modified by JAK inhibitors leading to poor immunity and recurrent infections. Hence, these drugs are used in treating rheumatoid arthritis and reducing swelling and pain caused due to it. In addition, the patients under JAK inhibitors should be monitored to prevent serious infections.
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Dr. Vishal Patidar
Dr. Vishal Patidar

General Medicine


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