NORTH CHICAGO, Ill., November 11, 2022 – AbbVie (NYSE: ABBV) announced today the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted an opinion following a nine-month review of the benefit-risk of medicines within the Janus kinase (JAK) inhibitor class for the treatment of inflammatory diseases, including RINVOQ® (upadacitinib). The CHMP did not recommend changes to current RINVOQ indication statements.
Further, the CHMP has confirmed the recommendation from the Pharmacovigilance Risk Assessment Committee (PRAC) to update posology and special warnings and precautions for these products, as follows:
- For high risk patients, defined as those aged 65 years or above, those at increased risk of major cardiovascular factors (such as heart attack or stroke), those who smoke or have done so for a long time in the past and those at increased risk of cancer, all JAK inhibitors should only be used if no suitable treatment alternatives are available.
- All JAK inhibitors should be used with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE) other than those listed above.
- Further, the lowest dose should be used in patient groups who are at risk of VTE, cancer or major cardiovascular problems.
These recommendations will be forwarded to the European Commission, which will issue its final decision applicable to all member states of the European Union (EU), as well as Iceland, Liechtenstein, Northern Ireland and Norway, expected no later than January 2023. At the time of the EC decision, the changes to the posology and special warnings and precautions for use sections of the label will be applied to all JAK inhibitors indicated for the treatment of inflammatory diseases, as per the CHMP opinion. The PRAC recommendation and CHMP opinion do not impact the prescribing information for RINVOQ in countries outside of the EU1
"Patient safety is AbbVie’s utmost priority, and we have been actively engaged in the Article 20 procedure to evaluate the benefit-risk profile of all JAK inhibitors, including RINVOQ,” said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. “This CHMP opinion will provide important guidance to physicians in evaluating appropriate treatment choices for patients in the EU, and we remain confident in the benefit-risk profile of RINVOQ across its approved indications.”
The CHMP opinion to adopt the PRAC recommendations follows a nine-month, multi-step, Article 20 procedure carried out by the PRAC, a committee responsible for assessing and monitoring the safety of human medicines. In addition to submission of data and presentations from all Marketing Authorization Holders, the process also considered advice from an expert group of rheumatologists, dermatologists and gastroenterologists. The procedure was carried out by the European Medicines Agency (EMA) under Article 20 of Regulation EC No 726/2004 and was initiated following review of data from other Marketing Authorization Holders’ studies of other JAK inhibitors used for the treatment of inflammatory diseases.
A direct healthcare professional communication will be disseminated at the time of the EC decision. For more information about the Article 20 procedure, please visit https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki
Patients who have questions about their medicine should discuss them with their prescribing healthcare provider.
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.2
In the EU, RINVOQ is approved for the treatment of adults with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs; 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; for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated CRP and/or MRI, who have responded inadequately to NSAIDs; for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy; for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis; and 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.2
Phase 3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis, Crohn's disease, giant cell arteritis and Takayasu arteritis are ongoing.3,4,5,6,7
EU Indications and Important Safety Information about RINVOQ® (upadacitinib)2
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.
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.
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.
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.
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.
Important Safety Information
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
Immunosuppressive medicinal products
Use in combination with other potent immunosuppressants is not recommended.
Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population. Upadacitinib should be interrupted if a patient develops a serious or opportunistic infection.
Patients should be screened for TB before starting upadacitinib. Upadacitinib 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, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib. Consider interruption of upadacitinib if patient develops herpes zoster.
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 upadacitinib, in agreement with current immunization guidelines.
The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.
Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis.
RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care.
Upadacitinib 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 upadacitinib 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, upadacitinib should be interrupted until this diagnosis is excluded.
Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. If clinical features of DVT/PE occur, upadacitinib should be discontinued and patients should be evaluated and treated appropriately.
There is an increased risk of adverse reactions with the upadacitinib dose of 30 mg once daily in patients aged 65 years and older. The recommended dose for long-term use is 15 mg once daily for this patient population.
Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving upadacitinib. If a clinically significant hypersensitivity reaction occurs, discontinue upadacitinib and institute appropriate therapy.
The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA.
The most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose-dependent increased risks of infection and herpes zoster were observed with upadacitinib. The safety profile for upadacitinib 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 UC trials (≥3% of patients) with upadacitinib 45 mg, 30 mg or 15 mg were upper respiratory tract infection, blood CPK increased, acne, neutropaenia, rash, herpes zoster, hypercholesterolemia, folliculitis, herpes simplex, and influenza. The overall safety profile observed in patients with ulcerative colitis was generally consistent with that observed in patients with RA.
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/en.
Globally, prescribing information varies; refer to the individual country product label for complete information.
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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
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 Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema) (Measure Up 1). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03569293
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 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
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 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. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03345836
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