AbbVie Provides Update on RINVOQ® for the Treatment of Rheumatoid Arthritis in the U.S.

ABBVie (NYSE: ABBV) today announced an update to the U.S. Prescribing Information and Medication Guide for RINVOQ ® (upadacitinib) for the treatment of adults with moderate to severe rheumatoid arthritis (RA). This update follows a Drug Safety Communication (DSC) issued on Sept. 1, 2021 by the U.S. Food and Drug Administration (FDA) following its final review of the post-marketing study, ORAL Surveillance, evaluating XELJANZ ® (tofacitinib) in patients with RA. 1 The results of this study showed a higher rate of major adverse cardiac events (MACE), malignancy, mortality and thrombosis in XELJANZ (a Janus kinase (JAK) inhibitor) versus TNF blockers. 1 The DSC and this label update apply to the class of systemically administered FDA-approved JAKs indicated for the treatment of RA and other inflammatory diseases. 1

Based on this class-wide update, the U.S. label for RINVOQ will now include additional information about the risks of malignancy and thrombosis, and the addition of mortality and MACE (defined as cardiovascular death, myocardial infarction and stroke) risks within the Boxed Warnings and Warnings and Precautions sections. ¹ The indication has also been updated to the following: RINVOQ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers. ¹

"RINVOQ is an important treatment option for people living with rheumatoid arthritis, especially those who have not been able to achieve remission or low disease activity. We remain committed to continue generating evidence that support its benefit-risk profile across many inflammatory conditions," said Michael Severino , M.D., vice chairman and president, AbbVie.

Supplemental New Drug Applications (sNDAs) for upadacitinib (RINVOQ) in atopic dermatitis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis remain under review by the FDA.

About RINVOQ ^® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2. ² The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. RINVOQ 15 mg is approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers. RINVOQ 15 mg is also approved by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. RINVOQ is approved by the European Commission for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis. Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing. ^3-10

Important Safety Information about RINVOQ® (upadacitinib)

RINVOQ U.S. Use and Important Safety Information  
RINVOQ is a prescription medicine used to treat moderate to severe rheumatoid arthritis in adults when one or more tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
  RINVOQ may cause serious side effects, including:

• Serious infections. RINVOQ can lower the ability of your immune system to fight infections. Some people have had serious infections while taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your healthcare provider (HCP) should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You should not start taking RINVOQ if you have any kind of infection unless your HCP tells you it is okay. You may be at higher risk of developing shingles (herpes zoster).
• Increased risk of death in people 50 years and older who have at least 1 heart disease (cardiovascular) risk factor.
• Cancer and immune system problems. Lymphoma and other cancers, including skin and lung cancers, can happen. People taking RINVOQ have a higher risk of certain cancers, including lymphoma and lung cancer, especially if you are a current or past smoker.
• Increased risk of major cardiovascular (CV) events such as heart attack, stroke, or death in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially if you are a current or past smoker.
• Blood Clots. Blood clots in the veins of the legs or lungs and arteries can happen in some people taking RINVOQ. This may be life-threatening and cause death. Blood clots in the veins of the legs and lungs have happened more often in people who are 50 years and older and with at least 1 heart disease (CV) risk factor.
• Tears in the stomach or intestines and changes in certain laboratory tests can happen. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.

What should I tell my HCP BEFORE starting RINVOQ?
Tell your HCP if you:

• Are being treated for an infection, have an infection that won't go away or keeps coming back, or have symptoms of an infection such as:

• Have TB or have been in close contact with someone with TB.
• Are a current or past smoker.
• Have had a heart attack, other heart problems, or stroke.
• Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or blood clots in the veins of your legs or lungs, diverticulitis (inflammation in parts of the large intestine), or ulcers in your stomach or intestines.
• Have other medical conditions including liver problems, low blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
• Live, have lived, or have traveled to parts of the country that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these areas, ask your HCP.
• Have recently received or are scheduled to receive a vaccine. People who take RINVOQ should not receive live vaccines.
• Are pregnant or plan to become pregnant. Based on animal studies, RINVOQ may harm your unborn baby. Your HCP will check whether or not you are pregnant before you start RINVOQ. You should use effective birth control (contraception) to avoid becoming pregnant while taking RINVOQ and for at least 4 weeks after your last dose.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. You should not breastfeed while taking RINVOQ and for at least 6 days after your last dose.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RINVOQ and other medicines may affect each other, causing side effects.

Especially tell your HCP if you take:

• Medicines for fungal or bacterial infections
• Rifampicin or phenytoin
• Medicines that affect your immune system

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I do or tell my HCP AFTER starting RINVOQ?

• Tell your HCP right away if you have any symptoms of an infection. RINVOQ can make you more likely to get infections or make any infections you have worse.
• Get emergency help right away if you have any symptoms of a heart attack or stroke while taking RINVOQ, including:
• discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
• severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• pain or discomfort in your arms, back, neck, jaw, or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded
• weakness in one part or on one side of your body
• slurred speech
• Tell your HCP right away if you have any signs or symptoms of blood clots during treatment with RINVOQ, including:

• Tell your HCP right away if you have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are the common side effects of RINVOQ?
These include upper respiratory tract infections (common cold, sinus infections), nausea, cough, and fever. These are not all the possible side effects of RINVOQ.

How should I take RINVOQ?
RINVOQ is taken once a day with or without food. RINVOQ is available in 15 mg extended-release tablets. Do not split, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it.

This is the most important information to know about RINVOQ. For more information, talk to your HCP.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

Please click here for the Full Prescribing Information and Medication Guide .

Globally, prescribing information varies; refer to the individual country product label for complete information .

About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html .

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , Instagram , YouTube and LinkedIn .

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:
1. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. FDA.gov. 2021. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death . Accessed: November 2021 .
2. RINVOQ ^® (upadacitinib) [Package Insert]. North Chicago, Ill. : AbbVie Inc.
3. Burmester G.R., et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
4. A Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635 . Accessed: November 2021.
5. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649 . Accessed: November 2021.
6. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202 . Accessed: November 2021.
7. A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (SELECT-PsA 2). Clinicaltrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104374 . Accessed: November 2021.
8. A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397 . Accessed: November 2021.
9. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373 . Accessed: November 2021.
10. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. 2020. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898 . Accessed: November 2021.

SOURCE AbbVie