NORTH CHICAGO, Ill.,
Dec. 18, 2019 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced that the European
Commission (EC) has approved RINVOQ™
(upadacitinib) for the treatment of adult patients 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 (DMARDs).6 RINVOQ is a once-daily
selective and reversible JAK inhibitor and may be used as
monotherapy or in combination with methotrexate (MTX).
"We are proud to offer this once-daily tablet as a new treatment
option for patients with moderate to severe active rheumatoid
arthritis," said Michael Severino,
M.D., vice chairman and president, AbbVie. "As a company that has
been dedicated to discovering and delivering transformative
therapies for people living with rheumatic diseases for nearly two
decades, RINVOQ expands our portfolio of treatment options for
people living with this disease in Europe."
The EC approval of RINVOQ was supported by data from the global
Phase 3 SELECT rheumatoid arthritis program, which evaluated nearly
4,400 patients with moderate to severe active rheumatoid arthritis
in five pivotal studies: SELECT-NEXT, SELECT-BEYOND,
SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY.1-5
The studies include assessments of efficacy, safety and
tolerability across a variety of patients, including those who
failed or were intolerant to biologic DMARDs and who were naïve or
inadequate responders (IR) to MTX.1-5
"Nearly 3 million people in Europe are living with rheumatoid arthritis,
the majority of whom don't reach remission and may be suffering
from pain, fatigue, morning joint stiffness and flares," said
Professor Ronald van Vollenhoven,
M.D., Ph.D., Amsterdam Rheumatology and Immunology Center,
Amsterdam, The Netherlands. "As
seen in this large Phase 3 clinical trial program in rheumatoid
arthritis, upadacitinib has the potential to significantly improve
signs and symptoms of the disease and help more patients achieve
remission or low disease activity."
Highlights From the Phase 3 SELECT Rheumatoid Arthritis
Program
Across the SELECT Phase 3 studies, RINVOQ met all primary and
ranked secondary endpoints.1-6 Overall, both low disease
activity (assessed by DAS28-CRP≤3.2) and clinical remission rates
(assessed by DAS28-CRP<2.6) were consistent across patient
populations, with or without MTX.1-6
Highlights included:
- In SELECT-COMPARE, RINVOQ plus MTX demonstrated significantly
higher remission rates (as observed by DAS28-CRP<2.6) versus
placebo plus MTX (29 percent vs 6 percent at week 12;
multiplicity-controlled p≤0.001) and vs HUMIRA®
(adalimumab) plus MTX (29 percent vs 18 percent at week 12; nominal
p≤0.001) in MTX-IR patients.4
- More patients treated with RINVOQ alone achieved remission (as
observed by DAS28-CRP<2.6) than those treated with MTX in MTX-IR
patients in SELECT-MONOTHERAPY (28 percent vs 8 percent at week 14;
multiplicity-controlled p≤0.0001) and in MTX-naïve patients in
SELECT-EARLY (48 percent vs 18 percent at week 24;
multiplicity-controlled p<0.001).3,5
- RINVOQ also demonstrated significantly greater inhibition of
structural joint damage progression, as measured by modified total
Sharp score change from baseline, as monotherapy compared to MTX
(0.1 vs 0.7 at week 24; multiplicity-controlled p<0.01) in
MTX-naïve patients and in combination with MTX compared to placebo
plus MTX (0.2 vs 0.9 at week 26; multiplicity-controlled p≤0.001)
in MTX-IR patients.4,5
- The most commonly reported adverse drug reactions were upper
respiratory tract infections (13.5 percent), nausea (3.5 percent),
blood creatine phosphokinase increased (2.5 percent) and cough (2.2
percent).6 The most common serious adverse reactions
were serious infections.1-6
More information on these trials can be found at
www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159,
NCT02706873, NCT02706951).
Earlier this year, RINVOQ received approval from the U.S. Food
and Drug Administration (FDA) for the treatment of adults with
moderately to severely active rheumatoid arthritis who have had an
inadequate response or intolerance to MTX.9
About RINVOQ (upadacitinib) in the European
Union6
RINVOQ (upadacitinib) is indicated for the treatment of moderate
to severe active rheumatoid arthritis 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.
Important EU Safety Information6
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.
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/oesophageal
candidiasis, and cryptococcosis have been reported with
upadacitinib. Prior to initiating upadacitinib, consider the risks
and benefits of treatment in patients with chronic or recurrent
infection or with a history of a serious or opportunistic
infection, in patients who have been exposed to TB or have resided
or travelled in areas of endemic TB or endemic mycoses, and in
patients with underlying conditions that may predispose them to
infection. Upadacitinib therapy should be interrupted if a patient
develops a serious or opportunistic infection. As there is a higher
incidence of infections in patients ≥75 years of age, caution
should be used when treating this population.
Patients should be screened for TB before starting upadacitinib
therapy. Anti-TB therapy should be considered prior to initiation
of upadacitinib in patients with previously untreated latent TB or
in patients with risk factors for TB infection.
Viral reactivation, including cases of herpes zoster, were
reported in clinical studies. Consider interruption of therapy if a
patient develops herpes zoster until the episode resolves.
Screening for viral hepatitis and monitoring for reactivation
should be performed before starting and during therapy with
upadacitinib.
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). Immunomodulatory medicinal
products may increase the risk of malignancies, including lymphoma.
The clinical data are currently limited and long-term studies are
ongoing. Malignancies, including non-melanoma 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.
Absolute neutrophil count <1000 cells/mm3,
absolute lymphocyte count <500 cells/mm3, or
haemoglobin levels <8 g/dL were reported in <1% of
patients in clinical trials. Treatment should not be initiated, or
should be temporarily interrupted, in patients with these
haematological abnormalities observed during routine patient
management.
RA patients have an increased risk for cardiovascular disorders.
Patients treated with upadacitinib should have risk factors (e.g.,
hypertension, hyperlipidaemia) managed as part of usual standard of
care.
Upadacitinib treatment was associated with increases in lipid
parameters, including total cholesterol, low-density lipoprotein
cholesterol, and high-density lipoprotein cholesterol. The effect
of these lipid parameter elevations on cardiovascular morbidity and
mortality has not been determined.
Treatment with upadacitinib was associated with an increased
incidence of liver enzyme elevation compared to placebo. If
increases in ALT or AST are observed during routine patient
management and drug-induced liver injury is suspected, upadacitinib
therapy 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. Risk factors that should be considered in
determining the patient's risk for DVT/PE include older age,
obesity, a medical history of DVT/PE, patients undergoing major
surgery, and prolonged immobilisation. If clinical features of
DVT/PE occur, upadacitinib treatment should be discontinued and
patients should be evaluated promptly, followed by appropriate
treatment.
The most commonly reported adverse drug reactions are upper
respiratory tract infections (13.5%), nausea (3.5%), increased
blood creatine phosphokinase (2.5%), and cough (2.2%). The most
common serious adverse reactions were serious infections.
Please see the full SmPC for complete prescribing information at
www.EMA.europa.eu. Globally, prescribing information varies;
refer to the individual country product label for complete
information
About HUMIRA® in the European
Union10
HUMIRA, in combination with methotrexate, is indicated for the
treatment of moderate to severe, active rheumatoid arthritis in
adult patients when the response to disease-modifying
anti-rheumatic drugs, including methotrexate, has been
inadequate.
Important EU Safety Information10
HUMIRA is contraindicated in patients with active tuberculosis
or other severe infections such as sepsis, and opportunistic
infections and in patients with moderate to severe heart failure
(NYHA class III/IV). It is also contraindicated in patients
hypersensitive to the active substance or to any of the excipients;
serious allergic reactions including anaphylaxis have been
reported. The use of HUMIRA increases the risk of developing
serious infections which may, in rare cases, be life-threatening.
Rare cases of lymphoma and leukemia have been reported in patients
treated with HUMIRA. On rare occasions, a severe type of cancer
called hepatosplenic T-cell lymphoma has been observed and often
results in death. A risk for the development of malignancies in
patients treated with TNF-antagonists cannot be excluded. Rare
cases of pancytopenia, aplastic anaemia, demyelinating disease,
lupus, lupus-related conditions and Stevens-Johnson syndrome have
been reported in patients treated with HUMIRA. The most frequently
reported adverse events across all indications included respiratory
infections, injection site reactions, headache and musculoskeletal
pain.
Please see the full SmPC for complete prescribing information at
www.ema.europa.eu. Globally, prescribing information varies; refer
to the individual country product label for complete
information.
About AbbVie
AbbVie is a global, research and development-based
biopharmaceutical company committed to developing innovative
advanced therapies for some of the world's most complex and
critical conditions. The company's mission is to use its expertise,
dedicated people and unique approach to innovation to markedly
improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie on
Twitter, Facebook, LinkedIn or Instagram.
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, competition from
other products, challenges to intellectual property, difficulties
inherent in the research and development process, adverse
litigation or government action, and changes to laws and
regulations applicable to our industry. 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 2018 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. 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
- Burmester GR, et al. Safety and efficacy of upadacitinib in
patients with rheumatoid arthritis and inadequate response to
conventional synthetic disease-modifying anti-rheumatic drugs
(SELECT-NEXT): a randomised, double-blind, placebo-controlled phase
3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi:
10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 13.
- Genovese MC, et al. Safety and efficacy of upadacitinib in
patients with active rheumatoid arthritis refractory to biologic
disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a
double-blind, randomised controlled phase 3 trial. Lancet. 2018 Jun
23;391(10139):2513-2524. doi: 10.1016/S0140-6736(18)31116-4. Epub
2018 Jun 13.
- Smolen JS, et al. Upadacitinib as monotherapy in patients with
active rheumatoid arthritis and inadequate response to methotrexate
(SELECT-MONOTHERAPY): a randomised, placebo-controlled,
double-blind phase 3 study. Lancet. 2019. May 23. doi:
10.1016/S0140-6736(19)30419-2. Epub 2019 May 23.
- Fleischmann R, et al. Upadacitinib versus placebo or adalimumab
in rheumatoid arthritis and an inadequate response to methotrexate:
Results of a Phase 3, Double-Blind, Randomized Controlled Trial.
Arthritis and Rheumatology. 2019. Jul 9. doi:
10.1002/art.41032.
- van Vollenhoven R, et al. A Phase 3, Randomized, Controlled
Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in
MTX-Naïve Patients with Active Rheumatoid Arthritis. 2018 ACR/ARHP
Annual Meeting; 891.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co KG. Available at: www.ema.europa.eu
- Bevan S, et al. Fit For Work? Musculoskeletal Disorders in the
European Workforce. 2009. The Work Foundation.
- Ajeganova S. and Huizinga T. Sustained remission in rheumatoid
arthritis: latest evidence and clinical considerations. Ther Adv
Musculoskelet Dis. 2017 Oct;9(10):249-262. doi:
10.1177/1759720X17720366.
- RINVOQ™ (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
- HUMIRA [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co KG. Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf.
Accessed November 12, 2019.
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