NORTH CHICAGO, Ill., May 25, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the New England Journal of Medicine (NEJM) published results from the pivotal Phase 3 clinical trials – U-EXCEL, U-EXCEED and U-ENDURE – evaluating upadacitinib (RINVOQ^®) in adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to conventional therapy or a biologic agent.^1-4

The publication reports the safety and efficacy results of oral upadacitinib versus placebo in two induction studies (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE), evaluating the co-primary endpoints of clinical remission and endoscopic response. Data from this Phase 3 program formed the basis of the company's application for approval by regulatory agencies. Use of upadacitinib in Crohn's disease is approved in Great Britain, Russia, United Arab Emirates, the European Union, and most recently in the United States as of May 2023. 

About Crohn's Disease
Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea, abdominal pain and fatigue.^5-7 It is a progressive disease, meaning it gets worse over time.^5,7 Because the signs and symptoms of Crohn's disease are unpredictable, it causes a significant burden on people living with the disease—not only physically, but also emotionally and economically.⁸

About the U-EXCEED and U-EXCEL Induction Studies, and the U-ENDURE Maintenance Study^1-4 

The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of upadacitinib 45 mg as induction therapy and upadacitinib 15 mg and 30 mg as maintenance therapy in patients with moderately to severely active Crohn's disease. Topline results of the U-EXCEED and U-EXCEL induction studies were announced in December 2021 and February 2022. Topline results of the U-ENDURE maintenance study were announced in May 2022. Results from all three of these studies have also been presented at recent congresses. More information can be found on www.clinicaltrials.gov (U-EXCEED: NCT03345836, U-EXCEL: NCT03345849, U-ENDURE: NCT03345823).

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-2.⁹ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

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.^10-17

US Indications and Important Safety Information about RINVOQ^® (upadacitinib)⁹

USES

RINVOQ is a prescription medicine used to treat:

• Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
• Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
• Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
• Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used, and did not work well or could not be tolerated.
• Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
• Adults with moderate to severe Crohn's disease (CD) when 1 or more medicines called 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 with juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn's disease.

• Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.

RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.

It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about RINVOQ?

RINVOQ may cause serious side effects, including:

• Serious infections. RINVOQ can lower your ability to fight infections. Serious infections have happened 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. If you get a serious infection, your HCP may stop your treatment until your infection is controlled. 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. RINVOQ may increase your risk of certain cancers. Lymphoma and other cancers, including skin cancers, can happen. Current or past smokers are at higher risk of certain cancers, including lymphoma and lung cancer. Follow your HCP's advice about having your skin checked for skin cancer during treatment with RINVOQ. Limit the amount of time you spend in sunlight. Wear protective clothing when you are in the sun and use sunscreen.
• 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 with 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. 
• Allergic reactions. Symptoms such as rash (hives), trouble breathing, feeling faint or dizzy, or swelling of your lips, tongue, or throat, that may mean you are having an allergic reaction have been seen in people taking RINVOQ. Some of these reactions were serious. If any of these symptoms occur during treatment with RINVOQ, stop taking RINVOQ and get emergency medical help right away. 
• Tears in the stomach or intestines. This happens most often in people who take nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids. Get medical help right away if you get stomach-area pain, fever, chills, nausea, or vomiting. 
• Changes in certain laboratory tests. 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.

Do not take RINVOQ if you are allergic to upadacitinib or any of the ingredients in RINVOQ. See the Medication Guide or Consumer Brief Summary for a complete list of ingredients.

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 or have had any type of cancer, hepatitis B or C, shingles (herpes zoster), 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, such as the Ohio and Mississippi River valleys and the Southwest, that increase your risk of getting certain kinds of fungal infections. If you are unsure if you've been to these types of 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 during treatment with RINVOQ and for 4 weeks after your last dose.
• There is a pregnancy surveillance program for RINVOQ. The purpose of the program is to collect information about the health of you and your baby. If you become pregnant while taking RINVOQ, you are encouraged to report the pregnancy by calling 1-800-633-9110.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. Do not breastfeed during treatment with RINVOQ and for 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

If you are not sure if you are taking any of these medicines, ask your HCP or pharmacist.

What should I avoid while taking RINVOQ?

Avoid food or drink containing grapefruit during treatment with RINVOQ as it may increase the risk of side effects.

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 other possible side effects of RINVOQ?

Common side effects include upper respiratory tract infections (common cold, sinus infections), shingles (herpes zoster), herpes simplex virus infections (including cold sores), bronchitis, nausea, cough, fever, acne, headache, increased blood levels of creatine phosphokinase, allergic reactions, inflammation of hair follicles, stomach-area (abdominal) pain, increased weight, flu, tiredness, lower number of certain types of white blood cells (neutropenia, lymphopenia, leukopenia), muscle pain, flu-like illness, rash, increased blood cholesterol levels, increased liver enzyme levels, pneumonia, low number of red blood cells (anemia), and infection of the stomach and intestine (gastroenteritis).

A separation or tear to the lining of the back part of the eye (retinal detachment) has happened in people with atopic dermatitis treated with RINVOQ. Call your HCP right away if you have any sudden changes in your vision during treatment with RINVOQ.

Some people taking RINVOQ may see medicine residue (a whole tablet or tablet pieces) in their stool. If this happens, call your healthcare provider.

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. Do not split, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it. RINVOQ is available in 15 mg, 30 mg, and 45 mg extended-release tablets.

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.

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 our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram. 

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 and uses of future or conditional verbs, 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2022 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, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. 

References:

1. Abbvie, Ltd. RINVOQ (upadacitinib) [summary of product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Accessed on December 7, 2022.
2. Colombel, J.F., Panes, J., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Induction Therapy in Patients with Moderately to Severely Active Crohn's Disease Who Failed Prior Biologics: Results from a Randomized Phase 3 U-EXCEED Study. UEG Journal. 2022;S-1934. Accessed on December 12, 2022.
3. Loftus, E., Colombel, L.F., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Induction Therapy in Patients with Moderately to Severely Active Crohn's Disease: Results from a Randomized Phase 3 U-EXCEL Study. UEG Journal. 2022; 10(8): 103-104. doi/10.1002/ueg2.12293. Accessed on December 12, 2022.
4. Panes, J., Loftus, E., Lacerda, A.P., et al. Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients with Moderately to Severely Active Crohn's Disease: Results from a Randomized Phase 3 U-ENDURE Maintenance Study. American College of Gastroenterology. 2022: 1-14. Accessed on December 12, 2022.
5. The Facts about Inflammatory Bowel Diseases. Crohn's & Colitis Foundation of America. 2014. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf. Accessed on February 13, 2023.
6. Kaplan, G. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7. doi: 10.1038/nrgastro.2015.150.
7. Crohn's disease. Symptoms and Causes. Mayo Clinic. 2022. Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304. Accessed on February 13, 2023.
8. Mehta F. Report: economic implications of inflammatory bowel disease and its management. Am J Manag Care. 2016 Mar;22(3 Suppl):s51-60
9. RINVOQ^® (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
10. A study comparing upadacitinib (ABT-494) to placebo and to adalimumab in adults with rheumatoid arthritis who are on a stable dose of methotrexate and who have an inadequate response to methotrexate (SELECT-COMPARE). ClinicalTrials.gov identifier: NCT02629159. Accessed February 14, 2023. https://www.clinicaltrials.gov/ct2/show/NCT02629159.
11. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on February 14, 2023.
12. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on February 14, 2023.
13. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (SELECT - PsA 1). ClinicalTrials.gov.  Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on February 14, 2023.
14. A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov.  Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on February 14, 2023.
15. Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898. Accessed on November 8, 2022.
16. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on February 14, 2023.
17. SKYRIZI [Summary of Product Characteristics]. AbbVie Ltd. Available at: https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf. Accessed on February 14, 2023.