AbbVie Presents Long-Term Data Further Supporting the Efficacy and Safety Profile of RINVOQ (upadacitinib) in Adults and Adolescents with Moderate to Severe Atopic Dermatitis

• Three ongoing, randomized, double-blind, multicenter Phase 3 studies demonstrated the long-term efficacy and safety profile of RINVOQ^® (upadacitinib) in treating moderate to severe atopic dermatitis based on results across 140 weeks¹
• Response rates for EASI 75 and vIGA-AD 0/1 (co-primary endpoints) and for EASI 90 and WP-NRS 0/1 at week 16 were sustained through week 140 among patients treated with RINVOQ¹
• Safety results were consistent with the known safety profile of upadacitinib, with no new safety signals observed¹
• Data will be presented as an oral presentation at the 32nd European Academy of Dermatology and Venereology (EADV) Congress

NORTH CHICAGO, Ill., Oct. 11, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new data analyses from the Measure Up 1, Measure Up 2 and AD Up Phase 3 studies that further demonstrated the long-term efficacy and safety profile of RINVOQ^® (upadacitinib) among adults and adolescents 12 years and older with moderate to severe atopic dermatitis through 140 weeks. Study results will be orally presented on Wednesday, October 11, at the 32nd European Academy of Dermatology and Venereology (EADV) Congress in Berlin.

"Patients with moderate to severe atopic dermatitis often face relentless itch and inflammatory skin symptoms that can impact their everyday lives," said Mudra Kapoor, M.D., vice president, global medical affairs, immunology, AbbVie. "These results reinforce our commitment to providing an effective, long-term treatment option for those living with this debilitating disease and other chronic, immune-mediated conditions."

In the Measure Up 1, Measure Up 2 and AD Up Phase 3 studies, a significantly higher proportion of patients treated with upadacitinib (15 mg or 30 mg) achieved the co-primary endpoints of improvement in skin clearance, measured by an EASI score of 75 (EASI 75) and vIGA-AD 0/1 at week 16, compared to those who received placebo.¹ Additionally, more upadacitinib-treated patients achieved the secondary endpoint of improvement in skin clearance, measured by an EASI score of 90 (EASI 90), and an additional endpoint of itch reduction (WP-NRS 0/1) at week 16, compared to placebo-treated patients.¹ The efficacy of both upadacitinib doses was consistently maintained for these important measures across all three studies through week 140.¹

Upadacitinib (15 mg and 30 mg) was generally well tolerated, and the safety data in the long-term extension of the three studies were consistent with the known safety profile of upadacitinib, with no new safety signals observed.¹ These results demonstrated that when taken continuously for a long-term period, upadacitinib has an acceptable benefit and risk profile for the treatment of moderate to severe atopic dermatitis. 

 Additionally, the most common adverse events across all three studies were COVID-19, upper respiratory tract infection, acne and nasopharyngitis.¹ The full safety data for these studies will be presented at EADV.

"We are encouraged by these results as they solidify upadacitinib's potential to improve care for people living with atopic dermatitis," said Jonathan Silverberg, M.D., Ph.D., MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Sciences. "While upadacitinib has been shown to be an effective treatment option for patients with atopic dermatitis in the short term, these data demonstrate a consistent safety profile and efficacy with long-term treatment."

About Measure Up²
Measure Up 1 and Measure Up 2 are Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled studies designed to evaluate the safety and efficacy of RINVOQ in adult and adolescent (12 years or older) patients with moderate to severe atopic dermatitis who are candidates for systemic treatment. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo. The co-primary endpoints were the percentage of patients achieving EASI 75 and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 after 16 weeks of treatment. Patients receiving placebo were switched to either RINVOQ 15 mg or RINVOQ 30 mg at week 16.

About AD Up³
AD Up is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult and adolescent (12 years or older) patients with moderate to severe atopic dermatitis who are candidates for systemic treatment. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo, all in combination with topical corticosteroids (TCS). The co-primary endpoints were the percentage of patients achieving EASI 75 and a vIGA-AD of 0/1 after 16 weeks of treatment. Patients receiving placebo plus TCS were switched to either RINVOQ 15 mg or RINVOQ 30 mg plus TCS at week 16.

About Atopic Dermatitis 
Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin.^4,5 It affects up to an estimated 10 percent of adults and 24.6 percent of adolescents.^5-7 Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.⁸ The range of symptoms poses significant physical, psychological and economic burden on individuals impacted by the disease.^5,9

About RINVOQ^® (upadacitinib)¹⁰
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor with seven approved indications and is currently being studied in several further immune-mediated diseases.¹⁰ In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.¹⁰

EU Indications and Important Safety Information about RINVOQ^® (upadacitinib)¹⁰
Indications

Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate.

Psoriatic arthritis
RINVOQ is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. RINVOQ may be used as monotherapy or in combination with methotrexate.

Axial spondyloarthritis
Non-radiographic axial spondyloarthritis (nr-axSpA)
RINVOQ is indicated for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).

Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)
RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

Atopic dermatitis
RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy.

Ulcerative colitis
RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Crohn's disease
RINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Important Safety Information

Contraindications
RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Special warnings and precautions for use
RINVOQ should only be used if no suitable treatment alternatives are available in patients:
-  65 years of age and older;
-  patients with history of atherosclerotic cardiovascular (CV) disease or other CV risk factors (such as current or past long-time smokers);
-  patients with malignancy risk factors (e.g. current malignancy or history of malignancy)

Use in patients 65 years of age and older
Considering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients ≥65 years of age, as observed in a large, randomized study of tofacitinib (another JAK inhibitor), RINVOQ should only be used in these patients if no suitable treatment alternatives are available. In patients ≥65 years of age, there is an increased risk of adverse reactions with RINVOQ 30 mg once daily. Consequently, the recommended dose for long-term use in this patient population is 15 mg once daily.

Immunosuppressive medicinal products
Use in combination with other potent immunosuppressants is not recommended.

Serious infections
Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis and sepsis have been reported with RINVOQ. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported. RINVOQ should not be initiated in patients with an active, serious infection, including localized infections. RINVOQ should be interrupted if a patient develops a serious or opportunistic infection until the infection is controlled. A higher rate of serious infections was observed with RINVOQ 30 mg compared to 15 mg. As there is a higher incidence of infections in the elderly and patients with diabetes in general, caution should be used when treating these populations. In patients ≥65 years of age, RINVOQ should only be used if no suitable treatment alternatives are available.

Tuberculosis
Patients should be screened for TB before starting RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy may be appropriate for select patients in consultation with a physician with expertise in the treatment of TB. Patients should be monitored for the development of signs and symptoms of TB.

Viral reactivation
Viral reactivation, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with RINVOQ. Consider interruption of RINVOQ if the patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should occur before and during therapy. If hepatitis B virus DNA is detected, a liver specialist should be consulted.

Vaccination
The use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating RINVOQ, in agreement with current immunization guidelines.

Malignancy
Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including RINVOQ. In a large randomised active‑controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma, and non-melanoma skin cancer (NMSC), was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. A higher rate of malignancies, including NMSC, was observed with RINVOQ 30 mg compared to 15 mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. In patients ≥65 years of age, patients who are current or past long-time smokers, or patients with other malignancy risk factors (e.g., current malignancy or history of malignancy), RINVOQ should only be used if no suitable treatment alternatives are available.

Hematological abnormalities
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.

Gastrointestinal Perforations
Events of diverticulitis and gastrointestinal perforations have been reported in clinical trials and from post–marketing sources. RINVOQ should be used with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or opioids. Patients with active Crohn's disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation.

Major adverse cardiovascular events
MACE were observed in clinical studies of RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of MACE, defined as CV death, non-fatal myocardial infarction and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors. Therefore, in patients ≥65 years of age, patients who are current or past long-time smokers, and patients with history of atherosclerotic CV disease or other CV risk factors, RINVOQ should only be used if no suitable treatment alternatives are available.

Lipids
RINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.

Hepatic transaminase elevations
Treatment with RINVOQ was associated with an increased incidence of liver enzyme elevation. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded.

Venous thromboembolism
Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a dose–dependent higher rate of VTE including DVT and PE was observed with tofacitinib compared to TNF inhibitors. In patients with CV or malignancy risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than CV or malignancy risk factors (e.g. previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder), RINVOQ should be used with caution. Patients should be re-evaluated periodically to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue RINVOQ in patients with suspected VTE.

Hypersensitivity reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving RINVOQ. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

Adverse reactions
The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with RINVOQ 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, neutropenia, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA.

The most commonly reported adverse reactions in AD trials (≥2% of patients) with RINVOQ 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, blood CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose dependent increased risks of infection and herpes zoster were observed with RINVOQ. The safety profile for RINVOQ 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated.

The most commonly reported adverse reactions in the UC and CD trials (≥3% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, blood CPK increased, anemia, headache, acne, herpes zoster, neutropaenia, rash, pneumonia, hypercholesterolemia, bronchitis, aspartate transaminase increased, fatigue, folliculitis, alanine transaminase increased, herpes simplex, and influenza.

The overall safety profile observed in patients with UC was generally consistent with that observed in patients with RA.

Overall, the safety profile observed in patients with CD treated with RINVOQ was consistent with the known safety profile for RINVOQ.

The most common serious adverse reactions were serious infections.

The safety profile of upadacitinib with long–term treatment was generally similar to the safety profile during the placebo–controlled period across indications.

This is not a complete summary of all safety information.

See RINVOQ full Summary of Product Characteristics (SmPC) at www.ema.europa.eu

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

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions 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, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn,Facebook, Instagram, X (formerly Twitter), and YouTube. 

AbbVie 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 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 to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:

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