- In patients with moderate to severe Crohn's disease who achieved clinical response to upadacitinib induction treatment, a significantly greater proportion treated with either 15 mg or 30 mg of upadacitinib achieved clinical remission,a,b endoscopic responsec and endoscopic remissiond at week 52 compared to placebo
- The safety results in this study were generally consistent with the known profile of upadacitinib, with no new safety risks observed
- Upadacitinib, a JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy for moderate to severe Crohn's disease and several other immune-mediated diseases
NORTH CHICAGO, Ill., May 11, 2022 /PRNewswire/ -- AbbVie today announced positive topline results from U-ENDURE, its Phase 3 maintenance study evaluating upadacitinib in adult patients with moderate to severe Crohn's disease who had an inadequate response or were intolerant to a conventional or biologic therapy. The results showed that more patients treated with either dose of upadacitinib (15 mg or 30 mg once daily) achieved the co-primary endpoints of endoscopic response and clinical remission, as well as the secondary endpoint of endoscopic remission, at one year (week 52) compared to placebo.1 Use of upadacitinib in Crohn's disease has not been evaluated by health authorities. Results from the U-ENDURE maintenance study, in addition to results from the U-EXCEED and U-EXCEL induction studies, will be included in future regulatory submissions.
In the U-ENDURE maintenance study, patients from U-EXCEED and U-EXCEL who responded to 12 weeks of upadacitinib 45 mg oral induction treatment were re-randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo. Clinical remission was defined by the Crohn's Disease Activity Index (CDAI) or by stool frequency and abdominal pain score (SF/AP).
A significantly higher proportion of patients who received upadacitinib 15 mg or 30 mg achieved clinical remission per the CDAI at week 52: 37 and 48 percent, respectively, versus 15 percent in the placebo group (p<0.0001).1 Results also showed that 36 and 46 percent of patients who received upadacitinib 15 mg and 30 mg, respectively, achieved clinical remission at week 52 per SF/AP compared to 14 percent in the placebo group (p<0.0001).1 At week 52, 28 and 40 percent of patients who received upadacitinib 15 mg and 30 mg, respectively, achieved endoscopic response compared to 7 percent of patients who received placebo (p<0.0001).1 In addition, 19 and 29 percent of patients who received upadacitinib 15 mg and 30 mg achieved endoscopic remission, respectively, compared to 5 percent of patients in the placebo group (p<0.0001).1 A significantly higher proportion of patients who received upadacitinib 15 mg or 30 mg achieved corticosteroid-free clinical remission per CDAI and per SF/AP compared to placebo at week 52 among patients taking corticosteroids at baseline.1
"We are deeply committed to supporting Crohn's disease patients who continue to live with challenging symptoms that impact their daily lives," said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. "These results represent important progress as we work to bring new treatment options to patients with inflammatory bowel disease."
"Symptomatic relief as well as healing of the intestinal mucosa in Crohn's disease are important long-term treatment targets which may be associated with slowing disease progression and better quality of life for patients," said Julian Panes, Emeritus Professor of Medicine and the Chief of the IBD Unit at Hospital Clínic de Barcelona and lead study investigator. "These results are encouraging and would be particularly important for patients who have not found relief with other conventional or biologic treatment options."
Efficacy Results at Week 52ꝉ
(n = 165)
Upadacitinib 15 mg
(n = 169)
Upadacitinib 30 mg
(n = 168)
Co-primary endpoints were clinical remission (per CDAI for the U.S. FDA and per SF/AP for the EU EMA) and endoscopic response at week 52.
ꝉ Efficacy was assessed after the first 502 patients reached week 52.
* Statistically significant with p-values of <0.0001 versus placebo.
a Clinical remission per CDAI is defined as CDAI <150.
b Clinical remission per SF/AP is defined as average daily very soft or liquid stool frequency ≤2.8 AND average daily abdominal pain score ≤1.0, and both not greater than baseline.
c Endoscopic response is defined as a decrease in Simplified Endoscopic Score for Crohn's disease (SES-CD) of >50 percent from baseline (or at least a 2-point reduction from baseline for patients with a baseline SES-CD of 4), as scored by central reviewer.
d Endoscopic remission is defined as SES-CD ≤ 4 and at least a 2-point reduction from baseline and no subscore > 1 in any individual variable, as scored by central reviewer.
The safety results of upadacitinib (15 mg or 30 mg) were generally consistent with the safety profile observed in the Phase 3 induction studies in Crohn's disease, as well as the known safety profile of upadacitinib. No deaths were reported throughout the study and no new safety risks were identified.
A total of 673 patients completed the 12-week upadacitinib induction treatment with clinical response and received at least one dose of the study drug in the placebo-controlled maintenance period. The most common adverse events in the upadacitinib groups were exacerbation of Crohn's disease, arthralgia and pyrexia.1 Serious adverse event and serious infection event rates per 100 patient years were the following for placebo, upadacitinib 15 mg, and upadacitinib 30 mg groups, respectively: 37.4/8.4, 25.0/6.1, 21.0/7.8. Malignancies (excluding non-melanoma skin cancer [NMSC]) reported in the study included one event in the upadacitinib 15 mg group, two events in the upadacitinib 30 mg group and no events in the placebo group.1 No adjudicated thrombotic events were reported in the upadacitinib 15 mg and placebo groups; one adjudicated hepatic vein thrombosis was reported in the upadacitinib 30 mg group.1 No adjudicated major adverse cardiovascular event (MACE) was reported in any treatment group.1 One patient each in the upadacitinib 15 mg, 30 mg and placebo groups experienced an event of adjudicated gastrointestinal perforation.1
The U-ENDURE Phase 3 study was designed to evaluate the efficacy and safety of upadacitinib as maintenance therapy versus placebo in patients with moderate to severe Crohn's disease who responded to upadacitinib induction treatment in the U-EXCEED or U-EXCEL induction studies. Full results from the U-ENDURE study maintenance period will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Use of upadacitinib in Crohn's disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
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 and abdominal pain.2,3 It is a progressive disease, meaning it gets worse over time in a substantial proportion of patients or may develop complications that require urgent medical care including surgery.2,3 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.2
The U-ENDURE study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled maintenance and long-term study designed to evaluate the efficacy and safety of upadacitinib 15 mg and 30 mg in adults with moderate to severe Crohn's disease. U-ENDURE enrolled patients who responded to 12 weeks of induction treatment from the U-EXCEED and U-EXCEL studies. In addition to the double-blind, placebo-controlled component, the U-ENDURE study also included patients from the induction studies who either responded to placebo or to extended treatment (an additional 12 weeks with 30 mg upadacitinib). During the study, patients who lost response were eligible to receive 30 mg upadacitinib as rescue therapy.
The study included slightly different sets of primary and secondary endpoints for the U.S. Food and Drug Administration (FDA) and the EU European Medicines Agency (EMA). The primary endpoints were achievement of clinical remission (per CDAI for the U.S. FDA, and per SF/AP for the EU EMA, which was measured by average daily very soft or liquid stool frequency and abdominal pain score) and endoscopic response (per SES-CD) at week 52. More information can be found on www.clinicaltrials.gov (NCT03345823).
About the Upadacitinib Phase 3 Crohn's Disease Program4,5,6
The global upadacitinib Phase 3 program evaluates more than 1,000 patients with moderate to severe Crohn's disease across two induction studies and a maintenance study. These studies include assessments of efficacy, safety and tolerability of upadacitinib. More information on these trials can be found at www.clinicaltrials.gov (NCT03345836, NCT03345849, NCT03345823).
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.7-14 Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK1 vs JAK2, JAK3, and TYK2.14 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.
Phase 3 trials of RINVOQ in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative colitis, giant cell arteritis, Takayasu arteritis and vitiligo are ongoing.7-14 The use of upadacitinib in Crohn's disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
RINVOQ® (upadacitinib) U.S. Use and Important Safety Information14
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with active psoriatic arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis 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 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, ulcerative colitis, or ankylosing spondylitis.
- Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) that did not respond to previous treatment and whose eczema is not well controlled with other pills or injections, including biologic medicines, or when 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.
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 and 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.
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:
- Fever, sweating, or chills
- Shortness of breath
- Warm, red, or painful skin or sores on your body
- Muscle aches
- Feeling tired
- Blood in phlegm
- Diarrhea or stomach pain
- Weight loss
- Burning when urinating or urinating more often than normal
- 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), 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.
- 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 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:
- Pain or tenderness in one or both legs
- Sudden unexplained chest or upper back pain
- Shortness of breath or difficulty breathing
- 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 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), muscle pain, flu-like illness, rash, increased blood cholesterol levels, and increased liver enzyme levels.
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.
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 http://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 Gastroenterology
With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.
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, LinkedIn or Instagram.
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 2021 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.
1 AbbVie. Data on File: ABVRRTI73939
2 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 January 11, 2022.
3 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 January 11, 2022.
4 A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Conventional and/or Biologic Therapies. ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03345849. Accessed on January 11, 2022.
5 A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy. ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03345836. Accessed on January 11, 2022.
6 A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Crohn's Disease Who Completed the Studies M14-431 or M14-433. ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03345823. Accessed on January 11, 2022.
7 Pipeline – Our Science | AbbVie. AbbVie. 2022. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on January 11, 2022.
8 A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on January 11, 2022.
9 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. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on January 11, 2022.
10 A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on January 11, 2022.
11 A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis (U-ACCOMPLISH). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed on January 11, 2022.
12 A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on January 11, 2022.
13 A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed on January 11, 2022.
14 RINVOQ® (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.