JAK inhibitors

Janus Kinase inhibitors (JAK inhibitors) are a newer class of prescription medications used to treat several autoimmune diseases and inflammatory disorders. These drugs help control an overactive immune system by blocking signals that cause inflammation. JAK inhibitors are small molecules taken by mouth or used topically, making them different from other biologics, which are usually given by injection or infusion. By calming immune responses, JAK inhibitors can improve symptoms, reduce flare-ups, and improve quality of life for people living with chronic inflammatory conditions.

JAK inhibitors are immunomodulating medications that work inside immune cells to reduce inflammation. They are used in rheumatology, dermatology, and gastroenterology to manage autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Unlike biologics that target one cytokine at a time, JAK inhibitors affect multiple inflammatory signals at once. Many of these medications are FDA-approved based on large clinical trials, including double-blind and placebo-controlled studies.

JAK inhibitors work by blocking the JAK-STAT pathway, a key signaling system used by cytokines to communicate inside immune cells. Cytokines bind to receptors on the cell surface, activating Janus kinases such as JAK1, JAK2, and tyrosine kinase 2 (TYK2). These kinases then activate signal transducer proteins that turn on inflammation-related genes. By inhibiting this intracellular process, JAK inhibitors reduce immune system overactivity. This inhibition helps lower inflammation in joints, skin, and the gut, which is why JAK inhibitors are useful in many inflammatory disorders.

There are several JAK inhibitors currently used in clinical practice. Each targets different Janus kinases:

• Tofacitinib (Xeljanz)
• Upadacitinib (Rinvoq)
• Baricitinib (Olumiant)
• Abrocitinib (Cibinqo)
• Ritlecitinib (Litfulo)
• Ruxolitinib (Jakafi)
• Filgotinib (Jyseleca)

Some medications are more selective for JAK1, while others affect JAK2 or TYK2. This selectivity can influence both effectiveness and side effects.

JAK inhibitors are used to treat a range of autoimmune diseases and inflammatory conditions, including:

• Treatment of rheumatoid arthritis, especially when methotrexate or other therapies have not worked
• Psoriatic arthritis and axial spondyloarthritis
• Ulcerative colitis and other forms of inflammatory bowel disease
• Moderate-to-severe atopic dermatitis (eczema)
• Psoriasis
• Alopecia areata
• Juvenile idiopathic arthritis
• Vitiligo

JAK inhibitors can cause side effects. Common side effects include:

• Upper respiratory infections
• Headache
• Nausea
• Acne
• Increased cholesterol levels
• Anemia and other blood cell changes

Serious adverse events include:

• Thromboembolism (blood clots)
• Heart attack
• Shingles (herpes zoster)
• Serious infections

Rare but serious risks include:

• Malignancies such as lymphoma
• Changes in liver enzymes

These are not all of the possible side effects of JAK inhibitors. You should always seek medical advice from your healthcare provider for any questions or concerns about your medical condition or treatment. Read all patient information, medication guides, or drug information sheets that come with this medication. You can also report adverse effects to the Food and Drug Administration at www.fda.gov/medwatch or 1-800-FDA-1088.

Although these medications are generally well-tolerated and safe, there are certain warnings, precautions, and drug interactions you should be aware of.

Warnings

Before starting JAK inhibitors, it is crucial to discuss any existing health conditions with your healthcare provider. You should be sure that your healthcare provider is aware of all your medical conditions, including if you have:

• A history of blood clots or thromboembolism
• Heart disease or prior heart attack
• Cancer or a history of malignancies
• Chronic or recurrent infections
• Liver or kidney disease
• Anemia or other blood disorders
• High cholesterol or metabolic risk factors

Vaccines should be reviewed before treatment, as live vaccines are usually avoided while taking JAK inhibitors.

Boxed Warning

Several JAK inhibitors carry a boxed warning from the US Food and Drug Administration. This warning highlights an increased risk of serious infections, blood clots, cardiovascular events, malignancies (including lymphoma), and death. These risks may be higher in older adults, people who smoke, or those with additional risk factors.

Contraindications

JAK inhibitors may not be appropriate for people with active serious infections, untreated tuberculosis, severe liver impairment, or known hypersensitivity to the medication. Your healthcare provider will weigh the benefits and risks before prescribing.

Drug interactions

When JAK inhibitors are taken with other prescription drugs, over-the-counter medications, vitamins, and supplements, it may change how they work or increase the frequency or severity of side effects. Make sure that you tell your healthcare professional about anything that you are taking to avoid any negative drug interactions, including:

• Other immunosuppressive drugs or biologics
• Methotrexate or other disease-modifying agents
• Certain antifungals or antibiotics that affect enzymes
• Medications that increase infection risk