AbbVie (NYSE: ABBV) today announced that the European Commission rate (EC) has approved RINVOQ ® (upadacitinib 15 mg, once daily), an oral therapy, for the treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) 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). *1
For years, healthcare providers and patients have had limited treatment options to manage axial spondyloarthritis, which can cause back pain, stiffness, plus irreversible damage to the particular spine, ” said Thomas Hudson, M. D., senior vice president of research and development, chief scientific officer, AbbVie. “AbbVie is proud to offer RINVOQ as a first-in-class treatment option now approved in the European Union for adults living with nr-axSpA with goal signs associated with inflammation and inadequate response to NSAIDs. RINVOQ is the first and only JAK inhibitor approved to treat patients across the spectrum of axial spondyloarthritis, which includes nr-axSpA plus ankylosing spondylitis. inch
Axial spondyloarthritis (axSpA) will be a chronic, progressive and disabling inflammatory rheumatic disease that causes joint inflammation, leading to back discomfort and stiffness. 3, 4, 5 AxSpA consists associated with two subsets that have been clinically defined as ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA), plus non-radiographic axial spondyloarthritis (nr-axSpA). 6 Approximately 10-40 percent of patients eventually progress from nr-axSpA in order to r-axSpA over a 2- to 10-year period. 7
The European Commission’s approval associated with RINVOQ for that treatment of nr-axSpA offers physicians within the European Union an important new therapeutic option along with proven efficacy in both nr-axSpA and AS patient populations, ” said Filip Van den Bosch, Meters. D., ** SELECT-AXIS 2 investigator and professor in the Department of Rheumatology at the University Hospital of Ghent University. “Living with nr-axSpA can pose many challenges plus significantly impact a patient’s quality of life. Early and effective disease management of individuals with active nr-axSpA is usually key to improving health outcomes. inch
AbbVie previously disclosed topline results from the Phase a few SELECT-AXIS two nr-axSpA clinical trial and the full results have been published in The Lancet . Study outcomes show a significantly greater proportion associated with patients receiving RINVOQ 15 mg achieved an Assessment of SpondyloArthritis international Society 40 percent (ASAS40) reaction at week 14 (45 percent versus 23 %; p< 0. 0001) compared to placebo. 2 Statistical significance was also achieved within 12 of the 14 multiplicity-controlled secondary endpoints compared in order to placebo at week 14. 2 Safety data were previously reported with no new risks identified compared to the known safety profile of RINVOQ. two Through 7 days 14, the particular proportion of patients who experienced an adverse event (AE) was similar between therapy groups (RINVOQ at 48 percent and placebo in 46 percent). 2
The particular EC Marketing Authorization for nr-axSpA means that RINVOQ is definitely approved in all member states of the Eu, as well as Iceland, Liechtenstein, Northern Ireland and Norway.
RINVOQ also recently received a label enhancement within the EU for your already approved indication associated with AS in order to include data on sufferers with energetic AS that had an inadequate response to biologic disease-modifying anti-rheumatic drugs (bDMARDs) based on the results of the particular Phase three or more SELECT-AXIS two clinical trial in this population, because well since two-year outcomes of the Phase 2/3 SELECT-AXIS 1 clinical test that evaluated AS bDMARD-naïve patients. 8, 9
AbbVie formerly disclosed topline results from the particular Phase several SELECT-AXIS 2 AS bDMARD-IR study, in which a lot better proportion of patients getting RINVOQ fifteen mg accomplished an ASAS40 response from week fourteen (45 percent versus 18 percent) in comparison to placebo. 8 All 14 ranked secondary endpoints were met including those evaluating improvements from baseline in disease activity, pain (total plus nocturnal back pain), function, MRI SPARCC score (spine), spinal mobility, enthesitis, and health-related standard of living. 8 Safety data were previously reported with no new risks identified compared to the known safety profile associated with RINVOQ. 8 Through week 14, the proportion of patients who experienced an AE was comparable between treatment groups (RINVOQ at 41 percent plus placebo with 37 percent). eight
About the SELECT-AXIS 1 and SELECT-AXIS two trial programs 2, 8 , nine
SELECT-AXIS 1 can be a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the particular safety plus efficacy of RINVOQ within adult individuals with active AS who are bDMARD-naïve and had inadequate response to at least two NSAIDs or intolerance to/contraindication with regard to NSAIDs. Period 2 is an open-label extension period to evaluate the long-term safety and efficacy associated with RINVOQ in subjects who else completed Time period 1. More information on this particular trial can be found at www.clinicaltrialsregister.eu/ (2017-000431-14) in the EU, and at www.clinicaltrials.gov (NCT03178487) within the U. S.
SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol plus includes two separate studies (SELECT-AXIS two AS (bDMARD-IR) study, or Study one and SELECT-AXIS 2 nr-axSpA study, or even Study 2).
Study 1: SELECT-AXIS 2 AS (bDMARD-IR) study 7
A randomized, double-blind, placebo-controlled Phase 3 demo, which examined the effectiveness and security of RINVOQ compared with placebo, in 420 patients along with a clinical diagnosis of AS which fulfilled the modified New York criteria, had BASDAI score ≥4 and total back discomfort score ≥4 (based on a numerical scale associated with 0-10), and had an inadequate response to bDMARD therapy.
Research 2: SELECT-AXIS 2 nr-axSpA study two
The randomized, double-blind, placebo-controlled, Stage 3 trial which evaluated the efficacy and protection of RINVOQ in contrast to placebo, in 314 patients with a medical diagnosis of nr-axSpA. Patients enrolled in the particular study experienced active indications of inflammation as indicated by MRI + sacroiliac combined inflammation, and high sensitivity C-reactive proteins (hs-CRP) > upper limit of normal (2. 87 mg/L) on screening, and who got BASDAI score ≥4 and a total back again pain rating ≥4 (based on a numerical scale of 0-10).
About Axial Spondyloarthritis (axSpA)
Axial spondyloarthritis is certainly a persistent inflammatory ailment that affects the particular spine, causing back pain, limited flexibility, and structural damage. 6 It consists associated with two subsets which have been medically understood to be radiographic axial SpA (ankylosing spondylitis) and non-radiographic axial spondyloarthritis (nr-axSpA). 6 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on X-rays. Non-radiographic axial spondyloarthritis is clinically defined by the absence associated with definitive X-ray evidence of structural damage to the sacroiliac (SI) joint simply by plain Xray. six
About RINVOQ ® (upadacitinib) 1
Discovered and developed by AbbVie scientists, RINVOQ is the selective JAK inhibitor that is being studied in several immune-mediated inflamed diseases. Within human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 along with functional selectivity over cytokine receptors that signal via pairs of JAK2.
In the particular EU, RINVOQ is approved regarding the treatment of adults with moderate in order to severe active rheumatoid arthritis who have replied inadequately to, or that are intolerant to one or more disease-modifying anti-rheumatic drugs; for the therapy of energetic psoriatic joint disease (PsA) within adult patients who have responded inadequately to, or even who are intolerant in order to one or even more DMARDs; for that treatment associated with active non-radiographic axial spondyloarthritis in adult patients along with objective signs of swelling as pointed out by raised CRP and/or MRI, that have responded improperly to NSAIDs; for the remedying of active ankylosing spondylitis (AS) in adult sufferers who possess responded badly to conventional therapy; intended for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis; and to get the treatment of grownup patients with moderately to severely energetic ulcerative colitis (UC) who also have had an inadequate reaction, lost response or had been intolerant in order to either standard therapy or a biologic agent. one
Phase 3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis and Takayasu arteritis are usually ongoing. 10, 11, 12, 13, 14, 15
EU Indications and Important Safety Information about RINVOQ ® (upadacitinib) 1
RINVOQ is indicated for the particular take care of mature patients along with moderately to severely active ulcerative colitis (UC) whom have recently had an inadequate reaction, lost response or were intolerant in order to either regular therapy or perhaps a biologic real estate agent.
RINVOQ is pointed out for the treatment of reasonable to serious 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 within combination with methotrexate.
RINVOQ is indicated for your treatment of energetic psoriatic joint disease (PsA) in adult most patients who have responded inadequately to, or who are intolerant in order to one or maybe more DMARDs. RINVOQ may be used because monotherapy or even in combination with methotrexate.
Non-radiographic axial spondyloarthritis (nr-axSpA)
RINVOQ is pointed out for the particular remedying of active non-radiographic axial spondyloarthritis within adult patients with objective signs of irritation as indicated by elevated C-reactive protein (CRP) and magnetic vibration imaging (MRI), who may have replied inadequately to nonsteroidal potent drugs (NSAIDs).
Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)
RINVOQ is pointed out to the therapy of energetic ankylosing spondylitis in grownup patients exactly who have responded inadequately in order to conventional treatment.
RINVOQ is indicated for the take care of moderate to severe atopic dermatitis (AD) in adults plus adolescents 12 years and older who are usually candidates pertaining to systemic therapy.
Essential Safety Information
RINVOQ is contraindicated within patients hypersensitive to the active substance or to any of the excipients, in patients along with active tuberculosis (TB) or even active serious infections, within patients with severe hepatic impairment, and during pregnancy.
Special warnings and precautions for use
Immunosuppressive medicinal products
Use in mixture with other potent immunosuppressants is not recommended.
Serious and sometimes fatal infections have got been documented individuals receiving upadacitinib. The most frequent severe infections reported included pneumoniand cellulitis. Cases of bacterial meningitis have been documented. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis happen to be reported along with upadacitinib. As there will be a higher incidence associated with infections in patients ≥65 years of age, caution should become used when treating this population. Upadacitinib should be interrupted if a patient develops a serious or opportunistic infection.
Individuals should end up being screened meant for TB before starting RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB treatment may be appropriate for select patients within consultation with a physician along with expertise in the treatment associated with TB. Sufferers must be monitored for any development of signs and symptoms of TB.
Viral reactivation, including cases of herpes zoster, was reported in medical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib. Consider interruption of upadacitinib if individual develops gürtelrose.
The use of live, attenuated vaccines during or immediately prior in order to therapy is not really recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.
The risk of malignancies, including lymphoma is usually increased in patients along with rheumatoid arthritis (RA). Malignancies, which includes nonmelanoma skin cancer (NMSC), are actually documented in sufferers treated with upadacitinib. Consider the dangers and benefits of upadacitinib treatment prior to initiating therapy in patients with the known malignancy other than a successfully handled NMSC or even when considering continuing upadacitinib treatment individuals who develop a malignancy. Periodic pores and skin examination is recommended for sufferers who are at increased risk for epidermis cancer.
Therapy must not be initiated, or should be temporarily interrupted, within patients with hematological abnormalities observed throughout routine affected person management.
Upadacitinib ought to be used along with caution in patients with diverticular illness and especially within patients chronically given concomitant medications associated with an increased risk associated with diverticulitis.
RA patients have an improved risk designed for cardiovascular disorders. Patients dealt with upadacitinib should possess risk factors (e. g., hypertension, hyperlipidemia) managed since part of usual standard of care.
Upadacitinib treatment was associated with dose-dependent increases in lipid parameters, including complete cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein bad cholesterol.
Hepatic transaminase elevations
Treatment with upadacitinib was connected with a greater incidence associated with liver enzyme elevation. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, upadacitinib needs to be interrupted until this diagnosis is excluded.
Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have already been reported within patients receiving JAK inhibitors, including upadacitinib. Upadacitinib ought to be used with caution in patients at high danger for DVT/PE. If scientific features associated with DVT/PE occur, upadacitinib need to be discontinued and patients should become evaluated plus treated appropriately.
There is a good increased risk of adverse reactions with the particular upadacitinib dose of 30 mg once daily within patients aged 65 years and old. The recommended dose just for long-term use is 15 magnesium once daily for this particular patient population.
The the majority of commonly reported side effects in RA, PsA, and axSpA clinical trials (≥2% of individuals in least 1 of the indications) with upadacitinib 15 mg were upper respiratory tract bacterial infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, cough, AST increased, and hypercholesterolemia. Overall, the safety user profile observed within patients along with psoriatic arthritis or energetic axial spondyloarthritis treated with upadacitinib 15 mg was consistent with the particular safety profile observed in sufferers with RA.
The most commonly reported adverse reactions in atopic hautentzündung trials (≥2% of patients) with upadacitinib 15 mg or thirty mg had been upper respiratory tract contamination, acne, herpes virus simplex, headache, CPK improved, cough, folliculitis, abdominal discomfort , nausea, neutropenia, pyrexia, and influenza. Dose-dependent increased risks of infection and herpes zoster were noticed with upadacitinib. The safety user profile for upadacitinib 15 magnesium in adolescents was similar to that will in adults. The protection plus efficacy associated with the 30 mg dosage in adolescents are still being investigated.
Probably the most generally reported undesirable reactions within UC tests (≥3% of patients) with upadacitinib 45 mg, thirty mg or even 15 magnesium were top respiratory tract infection, blood CPK improved, acne, neutropaenia, rash, herpes simplex virus zoster, hypercholesterolemia, folliculitis, herpes simplex, and influenza. The overall safety profile observed in patients along with ulcerative colitis was generally consistent with that seen in patients with RA.
The most common serious adverse reactions were severe infections.
The safety profile associated with upadacitinib with long term treatment was usually similar in order to the basic safety profile during the placebo-controlled period across indications.
This is not a complete summary of all safety information.
See RINVOQ full summary associated with product characteristics (SmPC) from www.ema.europa.eu/en .
Globally, prescribing information varies; refer to the individual country product label for complete information.
Regarding AbbVie within Rheumatology
With regard to more than 20 years, AbbVie has been dedicated to improving care for people residing with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html .
AbbVie’s mission is to discover and deliver innovative medicines that solve serious wellness issues today and address the medical challenges associated with tomorrow. We strive in order 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. To find out more about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , Instagram , YouTube and LinkedIn .
Some statements in this news release are usually, or might be considered, forward-looking statements with regard to purposes of the Private Securities Litigation Reform Act of 1995. The words “believe, ” “expect, ” “anticipate, ” “project” and comparable expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks plus uncertainties that may cause actual results to differ materially from all those indicated within 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 in order to promptly plus effectively integrate Allergan’s businesses, competition through 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 associated with public wellness outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that could 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 Percentage, as updated by the subsequent Quarterly Reports upon Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions in order to forward-looking claims as a result of subsequent events or developments, except as required by law.
*This recommendation is without prejudice to the final conclusions from the ongoing referral procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance information.
**Dr. Van living room Bosch is a consultant plus advisor regarding AbbVie.
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2 Deodhar, A, et al. Efficacy and Security of Upadacitinib in Patients with Active Non-Radiographic Axial Spondyloarthritis: the Double-Blind, Randomized, Placebo-Controlled Stage 3 Trial. EULAR 2022 Congress; 2534.
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4 Mayo Clinic. Ankylosing Spondylitis. 2019. Available with: https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptoms-causes/syc-20354808 . Accessed June 2022.
5 Dean, LE, ainsi que al. Global prevalence associated with ankylosing spondylitis. Rheumatology (Oxford). 2014 Apr; 53(4): 650-7. doi: ten. 1093/rheumatology/ket387. Epub 2013
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9 Vehicle der Heijde D, et al. Efficacy and Basic safety of Upadacitinib in Sufferers with Active Ankylosing Spondylitis: 2-Year Results from a Randomized, Double-Blind, Placebo-Controlled Study with Open-Label Extension [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10).
10 Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema) (Measure Up 1). ClinicalTrials. gov. 2021. Available on: https://clinicaltrials.gov/ct2/show/NCT03569293 . Accessed 06 2022.
11 A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT-AXIS 2). ClinicalTrials. gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373 . Accessed June 2022.
12 The Study in the Efficacy plus Safety associated with Upadacitinib (ABT-494) in Individuals With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or Are Intolerant in order to Biologic Treatment. ClinicalTrials. gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03345836 . Accessed June 2022.
thirteen A Research to judge the particular Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy within Participants Along with Moderately to Severely Energetic Ulcerative Colitis (UC). ClinicalTrials. gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635 . Accessed June 2022.
fourteen A Study in order to Evaluate the Safety and Effectiveness of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials. gov. 2021. Available in: https://clinicaltrials.gov/ct2/show/NCT03725202 . Accessed 06 2022.
15 A Study to gauge the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials. gov. 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04161898 . Accessed June 2022.