Upadacitinib/Elsubrutinib

This information is brought to you by the Lupus Research Alliance and Lupus Therapeutics and is not sponsored by, nor a part of, the American College of Rheumatology. 30+ presentations of studies funded by the LRA spanning a broad spectrum of research areas Positive results from Phase 2/3 clinical studies supported by LRA affiliate Lupus Therapeutics point to potential new treatments Lupus Therapeutics' PALS Program helps overcome challenges of diverse lupus patient trial participation SAN DIEGO, Nov. 6, 2023 /PRNewswire/ -- The Lupus Research Alliance (LRA), the largest non-governmental non-profit funder of lupus research worldwide, is pleased to announce results from more than 30 studies supported by the LRA and its clinical research affiliate Lupus Therapeutics will be presented at ACR Convergence 2023, the annual meeting of the American College of Rheumatology. Studies will represent the full continuum of research that the LRA and Lupus Therapeutics support, from innovative foundational research to lupus clinical trials evaluating potential new treatments. "The LRA and Lupus Therapeutics are extremely proud of the tremendous work we have supported that will contribute to the dynamic scientific dialogue at this important rheumatology meeting,' commented LRA President and CEO Albert T. Roy. "We also look forward to many presentations of exciting clinical research, including results from CAR-T cell therapy studies that built on pioneering work funded by the LRA and have the potential to shift the lupus treatment paradigm." FOUNDATIONAL RESEARCH FUNDED BY THE LRA LRA-funded investigators will be presenting their recent breakthroughs across a broad spectrum of lupus research, including the impact of lupus on various organs such as the skin, kidney, and brain, the contribution of the gut microbiome to lupus, dysregulation of a variety of immune cell types underlying lupus, and more. ORAL PRESENTATIONS Sunday, Nov. 12 APOL1 High Risk Genotype in SLE: A Genes in Context Story Abstract # NA, 12:00 PM – Room 11A-B ROCK1 Orchestrates B-cell Differentiation Under Stress Abstract #0729, 2:30 PM – Room 30D-E Lupus Nephritis Flares Linked to Platelet Activation During Gut Pathobiont Blooms Abstract #0851, 5:00 PM, Exhibit Hall A-B Monday, Nov. 13 CXCL13+ T cell differentiation in systemic lupus erythematosus is controlled by opposing effects of aryl hydrocarbon receptor and type I interferon Abstract #1580, 11:15 AM – Exhibit Hall A-B Metabolic Mechanisms that Control Inflammation and Immune-related Disorders Plenary Session II, 12:00 PM – Room 30D-E Keratinocyte VISTA Suppresses Skin IFN-I Production by Regulating DNA Damage Repair and Cytosolic DNA Sensing Abstract #1586, 2:15 PM – Room 32A-B Single-Cell RNA Sequencing Reveals Cellular Drivers of UV-mediated Skin Injury in Cutaneous Lupus Abstract #1599, 2:30 PM – Room 6F/6C Identifying Potential Neuroimaging Biomarkers of Neuropsychiatric Lupus in Children Using Deep Learning Abstract #1625, 3:00 PM – Room 7A-B Tuesday, Nov. 14 Longitudinal Gut Microbiome Analyses and Blooms of Pathogenic Strains during Lupus Disease Flares Abstract #NA, 8:20 AM – Room 6F/6C Development of Engineered Smith-Specific Regulatory T Cells to Treat Lupus Nephritis Abstract #2444, 2:15 PM – Room 26A-B Targeting of Endothelial Dysfunction in Lupus Nephritis: Effect on Human Renal Endothelial Cell Gene Expression and Outcomes in Murine Lupus Nephritis Abstract #2445, 2:30 PM – Room 26A-B UV Light Exposure Induces a Type I Interferon Dependent Activation and Migration of Inflammatory Dendritic Cells to Local Lymph Nodes Abstract #2448, 3:15 PM – Room 26A-B Wednesday, Nov. 15 In Situ Adaptive Immunity in Human Lupus Nephritis Abstract # N/A, 8:30 AM – Room 29A-D POSTER PRESENTATIONS – Poster Hall Sunday, Nov. 12 Elevated Serum Levels of S100A8/A9 Discriminate Systemic Lupus Erythematosus Patients with Cognitive Impairment from Patients Without Impairment Abstract #0558, 9:00 AM Comparison of Plasma Protein Profiles and Endothelial Function in Patients with Pediatric-Onset Systemic Lupus Erythematosus and Healthy Controls Abstract #0568, 9:00 AM Monday, Nov. 13 Specificity of Brain-Intrinsic and Hematopoietic-Derived Mechanisms in Mediating Neuropsychiatric Symptoms of Systemic Lupus Erythematosus Abstract #0890, 9:00 AM Adverse Childhood Experiences in a Paediatric Systemic Lupus Erythematosus Cohort Abstract #1241, 9:00 AM Agreement Between Parent- and Self-Report of Executive Function in Adolescents with Childhood-Onset Systemic Lupus Erythematosus Abstract #1242, 9:00 AM Proinflammatory Neutrophils and NETs Mediate Skin and Kidney Inflammation During Lupus Flare in Asymptomatic Lupus-prone Mice Triggered by UVB Abstract #0920, 9:00 AM IL-4 Acts Through Aryl Hydrocarbon Receptor to Antagonize TLR7-induced Double Negative 2 B Cells in Lupus Abstract #0925, 9:00 AM Examining the Relationship Between Socioenvironmental Factors and Cognitive Functioning in Youth with Childhood-Onset Systemic Lupus Erythematosus Abstract #1226, 9:00 AM Longitudinal Assessment of Self-reported Executive Function in Youth with Childhood-Onset Lupus Abstract #1229, 9:00 AM Complement Deposition on Extracellular Mitochondria Induces Platelet Activation in Vitro Abstract #0900, 9:00 AM The Cellular and Spatial Type I Interferon Response Following Skin Exposure to Ultraviolet Light Abstract #0894, 9:00 AM Tuesday, Nov. 14 Brain Activity Patterns and Behavioural Performance in SLE Patients During a Spatial Working Memory and Sustained Attention Task Abstract #2258, 9:00 AM The Effects of Systematic Lupus Erythematosus Related Cognitive Impairments on Activities of Daily Living and Life Role Participation: A Qualitative Framework Study Abstract #2259, 9:00 AM Association of Mycophenolate and Azathioprine Use with Cognitive Function in Systemic Lupus Using a Bayesian Longitudinal Item-response Theory Model Abstract #2290, 9:00 AM CLINICAL TRIALS SUPPORTED BY LUPUS THERAPEUTICS As the clinical research affiliate of the LRA, Lupus Therapeutics collaborates with biotechnology and pharmaceutical companies, as well as lupus experts from their Lupus Clinical Investigators Network (LuCIN) to help design and conduct high-quality, patient-centric, and diverse lupus studies, including several with results being presented at ACR Convergence 2023. ORAL PRESENTATIONS Tuesday, Nov. 14 Efficacy and Safety of ABBV-599 High Dose (Elsubrutinib 60 mg and Upadacitinib 30 mg) and Upadacitinib Monotherapy for the Treatment of Systemic Lupus Erythematosus: A Phase 2, Double-blind, Placebo-controlled Trial Abstract #2488, 2:00 PM – Ballroom 20D Phase 2 Safety and Efficacy of Subcutaneous (s.c.) Dose Ianalumab (VAY736; Anti-BAFFR mAb) Administered Monthly over 28 Weeks in Patients Abstract #2487, 2:00 PM – Ballroom 20D POSTER PRESENTATIONS – Poster Hall Monday, Nov. 13 Treatment with Upadacitinib in Patients with Systemic Lupus Erythematosus Results in the Inhibition of B-Cell–related Biomarkers: Analysis of the M19-130 (SLEek) Phase 2 Study Abstract #1489, 9:00 AM Disease Course and Complement as Predictors of Response to Standard of Care Plus Placebo in Patients with SLE: A Post Hoc Analysis of Dapirolizumab Pegol and Epratuzumab Clinical Trial Data Abstract #1503, 9:00 AM Steroid-sparing Effects of Afimetoran (BMS-986256), an Equipotent Toll-like Receptor (TLR)7 and TLR8 Antagonist, in a Lupus Mouse Model Abstract #0897, 9:00 AM Transcriptomic Analysis of the Impact of Iberdomide on Patients with SLE Abstract #1694, 4:00 PM Tuesday, Nov. 14 Dapirolizumab Pegol Impacts Important Immunologic Pathways in SLE: Pharmacodynamic Analysis of B Cell and Type I Interferon Pathways from a Phase 2b Trial Abstract #2333, 9:00 AM Modulation of B Cell and Interferon Pathways by Ianalumab in Patients with Systemic Lupus Erythematosus: Findings from a Phase 2 Clinical Trial Abstract #2342, 9:00 AM WORK CONDUCTED THROUGH THE LUPUS THERAPEUTICS PALS PROGRAM Patient Advocates for Lupus Studies (PALS) is a peer support program that aims to improve participation in lupus clinical trials through increased education and availability of information about clinical trials. Individuals living with lupus who have clinical research act as peer educators, or PALs, to deliver educational sessions to others living with lupus. The PALS program was piloted from 2019-2021 and demonstrated significant increases in knowledge about, attitudes toward, and intentions to participate in lupus clinical trials among program participants. POSTER PRESENTATION – Poster Hall Sunday, Nov. 12 Barriers and Facilitators to Recruiting Underrepresented Participants for Clinical Trials: Insights from the Lupus Clinical Investigators Network (LuCIN) Abstract #0183, 9:00 AM WORK CONDUCTED BY THE ACCELERATING MEDICINES PARTNERSHIP The LRA is a partner in Accelerating Medicines Partnership® Autoimmune Mediated Disease (AMP® AIM), which brings together 20 organizations from the public, private, and nonprofit sectors to accelerate the identification and validation of new therapeutic targets by reconstructing shared immune response pathways through spatial and multi-omics technologies. The project is managed by the FNIH and builds on the success of AMP RA/SLE in which LRA was also a partner. The presentation of results from an AMP® AIM lupus study is noted below. ORAL PRESENTATION Monday, Nov. 13 Single Cell Transcriptomics in Kidney Tissue from African American Patients Enrolled in the Accelerating Medicines Partnership (AMP) Implicates Tubular Cells in the Pathogenesis of APOL1 Associated Lupus Nephritis Abstract #1695, 4:30 PM – Room 6F/6C About Lupus Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women, often striking during the childbearing years of 15-45. Blacks/African Americans, Hispanics, Asians, and Native Americans are at two to three times greater risk than Caucasians for developing lupus. In lupus, the immune system, meant to defend against infections, produces antibodies that mistakenly recognize the body's own cells as foreign, prompting other immune cells to attack and potentially damage organs such as the kidneys, brain, heart, lungs, blood, skin, and joints. About Lupus Research Alliance The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately, cure for lupus. Because the Lupus Research Alliance's Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. About Lupus Therapeutics Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance, aims to accelerate the development of curative treatments for all patients living with lupus. Lupus Therapeutics collaborates with academic institutions, biotechnology, and pharmaceutical partners through the unprecedented Lupus Clinical Investigators Network (LuCIN) to drive rapid and meaningful progress in the treatment of lupus patients. The organization elevates the patient voice, engages community stakeholders, and strives for representation of the diverse lupus community in the clinical research process with the most innovative and renowned experts throughout North America. Visit lupustherapeutics.org for more information. SOURCE Lupus Research Alliance

- At week 24, upadacitinib 30 mg given alone or as a combination therapy (ABBV-599 high dose [elsubrutinib 60 mg and upadacitinib 30 mg]) met the primary endpoint of systemic lupus erythematosus (SLE) Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day in patients with moderately to severely active SLE receiving standard lupus therapies 1 - Upadacitinib maintained greater improvements in SLE disease activity at week 48 as measured by the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), SRI-4, Lupus Low Disease Activity State (LLDAS) and lupus flares compared with placebo 2 - No new safety signals were observed beyond the known safety profile for upadacitinib. Types of adverse events reported with ABBV-599 high dose were similar to those reported for patients treated with upadacitinib alone 2 - Study results are being presented as an oral presentation at the European Congress of Rheumatology, EULAR 2023 NORTH CHICAGO, IL, USA I May 31, 2023 I AbbVie (NYSE: ABBV) today announced the results of the Phase 2 SLEek study evaluating upadacitinib (RINVOQ ® 30 mg) alone and in combination [ABBV-599 high dose (elsubrutinib 60 mg and upadacitinib 30 mg)] in adults with moderately to severely active systemic lupus erythematosus (SLE) who continued to receive standard lupus therapies. The study results are being presented as an oral presentation during the European Congress of Rheumatology, EULAR 2023. In the Phase 2 SLEek study, a greater proportion of patients receiving upadacitinib 30 mg or ABBV-599 high dose achieved the primary endpoint, SLE Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24, compared to placebo (54.8 percent; p=0.028 and 48.5 percent; p=0.081* versus 37.3 percent, respectively). 1 SRI-4 and steroid dose less than or equal to 10 mg prednisone equivalent per day assess reductions in disease activity and glucocorticoid use, respectively. 3 "There are limited treatment options for people living with SLE, leaving physicians challenged on how to effectively slow disease progression and limit potential organ damage in their patients," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "As a leader in immunology, AbbVie is committed to advancing care in areas of unmet need, such as SLE. We are encouraged by these positive Phase 2 data and look forward to continuing to study upadacitinib for systemic lupus erythematosus in two Phase 3 trials as part of our ongoing clinical program." Key secondary endpoints were also achieved at week 48 in both active treatment groups, including lupus flares measured by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) and time to first flare, which showed greater treatment effect in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo. 2 Other measures of disease activity and treatment response were also met, including achievement of BICLA response, SRI-4, and Lupus Low Disease Activity State (LLDAS) in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo. 2 SLE—the most common type of lupus—is an autoimmune disease where the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. 4 It can impact the joints, skin, brain, lungs, kidneys and blood vessels, causing a variety of symptoms, including fatigue, skin rashes, fevers, and pain and swelling in the joints. 4 Disease activity in lupus—often called flares—is unpredictable. 5 Flares can appear without warning, come and go and vary in severity—serious flares can cause organ damage and require medical attention. 6 "Lupus is an imbalance in the immune system caused by a diverse set of inherited and environmental factors. It impacts over three million people around the world and causes an overlapping spectrum of symptoms," said Joan Merrill, M.D., Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program. "To achieve sustainable progress with SLE, we need more treatment options for patients with this disease." No new safety signals were observed beyond the known safety profile for upadacitinib. 2 Types of adverse events reported with ABBV-599 high dose were similar to those reported for patients treated with upadacitinib alone. 2 The rate of treatment emergent adverse events (TEAEs) in this study were similar across groups (ABBV-599 at 86.8 percent, upadacitinib at 82.3 percent and placebo at 78.7 percent). 2 Serious AEs were reported in 10.3 percent of patients in the ABBV-599 high dose, 21.0 percent in upadacitinib 30 mg, and 17.3 percent in placebo groups. 2 Adjudicated cardiovascular events were reported in one patient in each of the three treatment groups. 2 There were no reports of malignancies or venous thromboembolic events. 2 The use of upadacitinib and elsubrutinib in SLE are not approved and their safety and efficacy have not been evaluated by regulatory authorities. About the SLEek Phase 2 Study In the SLEek Phase 2 study, 341 patients undergoing standard lupus therapy were randomized to receive once daily ABBV-599 high dose, ABBV-599 low dose (elsubrutinib 60 mg plus upadacitinib 15 mg), elsubrutinib 60 mg, upadacitinib 30 mg or placebo. 2 After a planned interim analysis when 50 percent of patients reached week 24 or withdrew from the study, the ABBV-599 low dose and elsubrutinib 60 mg arms were discontinued for lack of efficacy. 205 patients continued in the study to week 48 (ABBV-599 HD n = 68, upadacitinib 30 mg n = 62, placebo n = 75). 2 As previously disclosed , AbbVie is advancing its clinical program of upadacitinib in SLE to Phase 3 based on these results. ABBV-599 will not move forward to Phase 3 due to no additional contribution of efficacy by elsubrutinib relative to upadacitinib alone. Additional results from the SLEek study are being presented at EULAR in posters 1133 and 1137. About RINVOQ ® (upadacitinib) Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. 7-20 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. 7 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known. 7 Upadacitinib (RINVOQ) is in Phase 3 development for giant cell arteritis, Takayasu arteritis and systemic lupus erythematosus. 14,18,20 EU Indications and Important Safety Information about RINVOQ ® (upadacitinib) 7 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 randomised 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 antiinflammatory 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 in Rheumatology For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Anchored by a longstanding commitment to discovering and delivering transformative therapies, we pursue cutting-edge science that improves our understanding of promising new pathways and targets, ultimately helping more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology . 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 . References SOURCE: AbbVie