Upadacitinib

Arthritis and Spinal Conditions

Upadacitinib is used in adults to treat several types of inflammatory joint and spine conditions, usually after other medications like tumor necrosis factor (TNF) blockers have been tried without success. These conditions include:

• Moderate to severe rheumatoid arthritis.
• Active psoriatic arthritis.
• Active ankylosing spondylitis.
• Active non-radiographic axial spondyloarthritis with objective signs of inflammation.

Inflammatory Bowel Disease

This medication is used for adults with moderate to severe cases of certain chronic digestive conditions when one or more TNF blockers have not worked well or were not tolerated:

• Ulcerative colitis: A condition causing inflammation and sores in the lining of the colon and rectum.
• Crohn's disease: A condition causing inflammation in any part of the digestive tract.

Atopic Dermatitis

Upadacitinib is used to treat moderate to severe atopic dermatitis (eczema) in adults and children 12 years of age and older. It is typically prescribed when the condition is not well controlled with other injectable or oral medications, or when those treatments are not appropriate.

Mechanism of Action

Upadacitinib belongs to a class of medications known as Janus kinase (JAK) inhibitors. It works by interfering with the signaling pathways inside certain immune cells. These pathways use enzymes called Janus kinases to send signals that trigger inflammation throughout the body.

In people with certain autoimmune or inflammatory conditions, the immune system becomes overactive and produces too many inflammatory signals. Upadacitinib specifically targets and blocks the JAK1 enzyme. By inhibiting this enzyme, the medication helps to:

• Decrease the production of inflammatory proteins.
• Reduce the swelling, pain, and redness associated with inflammation.
• Calm the overactive immune response that attacks healthy tissues.

By interrupting these internal communication lines, upadacitinib helps manage symptoms and prevent further damage caused by chronic inflammation in conditions like arthritis, skin disorders, and inflammatory bowel disease.

Common Side Effects

Many people using upadacitinib experience mild side effects. These may include:

• Upper respiratory tract infections, such as the common cold or sinus infections
• Nausea
• Cough
• Fever
• Acne or skin rash
• Headache
• Increased weight
• Fatigue
• Back pain

Serious Side Effects

Upadacitinib can cause serious, sometimes life-threatening side effects. Seek medical help immediately if you experience symptoms of the following:

• Serious Infections: This medication can weaken the immune system, making it harder to fight infections like tuberculosis (TB), shingles (herpes zoster), and fungal or bacterial infections.
• Blood Clots: Some patients have developed blood clots in the legs (deep vein thrombosis), lungs (pulmonary embolism), or arteries. Symptoms include sudden shortness of breath, chest pain, or swelling and tenderness in a limb.
• Heart-Related Events: There is an increased risk of major cardiovascular events, such as heart attack or stroke, particularly in people with existing risk factors or a history of smoking.
• Cancer: Use of this drug may increase the risk of developing certain cancers, including lymphoma, lung cancer, and non-melanoma skin cancers.
• Gastrointestinal Perforation: Tears in the stomach or intestines can occur. Symptoms include severe stomach pain, fever, and changes in bowel habits.
• Allergic Reactions: Signs of a severe reaction include hives, swelling of the face, lips, or throat, and difficulty breathing.
• Laboratory Changes: Upadacitinib may cause changes in blood tests, including elevated liver enzymes, increased cholesterol levels, and low white or red blood cell counts.

Boxed Warnings

Upadacitinib includes boxed warnings for several serious risks. These warnings are based on clinical data and observations of similar medications in the same drug class.

• Serious Infections: This medication may decrease the immune system's ability to fight infections. Serious and sometimes fatal infections, including tuberculosis, shingles, and various bacterial, fungal, or viral infections, have occurred.
• Increased Risk of Death: There is an increased risk of death in people 50 years of age and older who have at least one heart disease risk factor.
• Cancer: An increased risk of lymphoma, lung cancer, and other malignancies has been observed, particularly in current or former smokers.
• Cardiovascular Events: Major heart-related events, such as heart attack or stroke, can occur. This risk is higher in people who smoke or have existing heart disease risk factors.
• Blood Clots: Serious and sometimes fatal blood clots in the lungs, legs, or arteries have been reported.

General Precautions

Before and during treatment, healthcare providers typically monitor for several conditions:

• Gastrointestinal Issues: Tears in the stomach or intestines (perforations) can occur, especially in those using NSAIDs or corticosteroids.
• Laboratory Abnormalities: Treatment may cause low white blood cell counts, low red blood cell counts (anemia), elevated liver enzymes, or high cholesterol. Regular blood monitoring is necessary.
• Vaccinations: Live vaccines should not be administered during treatment.
• Pregnancy: This medication may cause fetal harm. Effective contraception is required during treatment and for four weeks after the final dose.

Pregnancy

Upadacitinib can cause harm to an unborn baby. Animal studies indicate that exposure to this medication during pregnancy may lead to birth defects. Healthcare providers typically advise individuals who can become pregnant to use effective birth control during treatment and for at least 4 weeks after the last dose.

If you are pregnant or planning to become pregnant, discuss the potential risks and benefits with your doctor. It is important to notify your healthcare provider immediately if you become pregnant while taking this medication.

Breastfeeding

It is unknown whether upadacitinib passes into human breast milk. Due to the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 6 days after the final dose. Consult with a healthcare professional to determine the best course of action for your situation.

Available Forms

Upadacitinib is currently available in the following form:

• Extended-release tablet: This is an oral tablet designed to release the medication slowly into the body over time.

Because these are extended-release tablets, they must be swallowed whole. They should not be crushed, chewed, or broken before swallowing.

FDA Approval and Indications

Upadacitinib was first approved by the U.S. Food and Drug Administration (FDA) in 2019. It is currently approved for the treatment of several conditions, typically after other treatments like tumor necrosis factor (TNF) blockers have been tried and were not effective or could not be tolerated. Approved uses include:

• Moderately to severely active rheumatoid arthritis.
• Active psoriatic arthritis.
• Active ankylosing spondylitis and non-radiographic axial spondyloarthritis.
• Refractory, moderate to severe atopic dermatitis in adults and children 12 years and older.
• Moderately to severely active ulcerative colitis.
• Moderately to severely active Crohn's disease.

Boxed Warning

The FDA requires a Boxed Warning for upadacitinib because it may increase the risk of serious and potentially fatal health events. These risks include:

• Serious Infections: Increased risk of developing serious infections, such as tuberculosis or shingles, which may lead to hospitalization or death.
• Mortality: A higher rate of death has been observed in patients 50 years and older with at least one cardiovascular risk factor taking JAK inhibitors.
• Malignancies: Increased risk of lymphoma and other cancers, including lung cancer and skin cancer.
• Major Cardiovascular Events: Increased risk of heart attack, stroke, and cardiovascular death, especially in smokers.
• Thrombosis: Increased risk of blood clots in the lungs, veins, or arteries.

Safety Updates

Following a review of safety data from clinical trials of drugs in the same class (JAK inhibitors), the FDA updated the prescribing information to include warnings about the increased risk of heart-related events and cancer. Because of these risks, the FDA has restricted the use of upadacitinib for most conditions to patients who have not responded to or cannot tolerate one or more TNF blockers.

Factors Influencing Cost

The price of upadacitinib can vary significantly based on several factors. Because it is a specialty medication, it is often handled differently by insurance providers than standard prescriptions.

• Insurance Plan: Your out-of-pocket costs will depend on your insurance company's formulary, your deductible, and your specific copay or coinsurance tier.
• Pharmacy Selection: Upadacitinib is often dispensed through specialty pharmacies, which may have different pricing structures than local retail pharmacies.
• Treatment Duration: The total cost is affected by the length of your treatment and the dosage prescribed for your specific condition.

Generic Status

There is currently no generic version of upadacitinib available. It is only sold under the brand name Rinvoq. Generic drugs typically become available only after the patent for the brand-name drug expires, which can take several years.

Financial Assistance

Many patients use financial assistance options to help cover the cost of this medication:

• Manufacturer Copay Cards: Patients with commercial insurance may be eligible for savings cards that lower their monthly copayments.
• Patient Assistance Programs: For those without insurance or with limited coverage, the manufacturer may provide the drug at a reduced cost or for free based on financial need.
• Insurance Navigation: Some programs help patients and healthcare providers manage the prior authorization process required by many insurance companies.