NORTH CHICAGO, Ill.,
June 2, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV) today announced new analyses to be
presented at the EULAR 2021 Virtual Congress showing patients with
moderate to severe rheumatoid arthritis on background methotrexate
(MTX) treated with RINVOQ® (upadacitinib, 15 mg, once
daily) maintained higher rates of clinical remission and low
disease activity through three years compared to those patients
treated with HUMIRA® (adalimumab).1
Additionally, a separate integrated safety analysis found the
safety profile of RINVOQ was consistent over 4.5 years, with no new
safety risks observed.2
"We are dedicated to helping more people living with rheumatoid
arthritis reach their treatment goals aimed at remission or low
disease activity," said Mudra Kapoor, M.D., rheumatology head,
global medical affairs, AbbVie. "These data reinforce the long-term
efficacy and safety profile of RINVOQ in rheumatoid arthritis. We
continue to advance research to provide valuable insights into the
role that RINVOQ has in helping patients with moderate to severe
rheumatoid arthritis."
SELECT-COMPARE Results at Three Years
In this study, a higher proportion of patients treated with
RINVOQ 15 mg achieved and maintained clinical remission and low
disease activity compared to those treated with HUMIRA, through
three years.1
Efficacy Results
from SELECT-COMPARE at 3 Years*,1
|
|
RINVOQ 15 mg plus
MTX
|
HUMIRA 40 mg EOW
plus
MTX
|
Clinical remission
per DAS28-CRP<2.6a
|
32%
|
22%
|
Clinical remission
per CDAI≤2.8b
|
24%
|
17%
|
Low Disease Activity
per DAS28-CRP≤3.2c
|
37%
|
26%
|
Low Disease Activity
per CDAI≤10d
|
39%
|
29%
|
|
|
*
|
Efficacy data
reported based on randomized treatment groups. For patients who
were rescued or prematurely discontinued, non-responder imputation
(NRI) was used for binary endpoints. Patients who received HUMIRA
were switched to receive RINVOQ 15 mg, and vice versa, if they did
not achieve at least a 20 percent improvement in both tender and
swollen joint count at weeks 14, 18 or 22 compared to baseline, or
if Clinical Disease Activity Index (CDAI) was greater than 10 at
week 26.
|
a
|
Clinical remission
per DAS28-CRP is defined as Disease Activity Score with 28 joint
counts C-reactive protein (DAS28-CRP) less than 2.6.
|
b
|
Clinical remission
per CDAI is defined as CDAI less than or equal to 2.8.
|
c
|
Low Disease Activity
per DAS28-CRP is defined as Disease Activity Score with 28 joint
counts C-reactive protein (DAS28-CRP) less than or equal to
3.2.
|
d
|
Low Disease Activity
per CDAI is defined as CDAI less than or equal to 10.
|
In addition to higher rates of clinical remission and low
disease activity, a higher proportion of patients treated with
RINVOQ 15 mg completed three years of treatment without rescue
compared to those treated with HUMIRA (46 percent versus 34
percent, respectively).1
In this study, through three years, the safety profile of RINVOQ
15 mg was consistent with the profile reported previously and with
that shown in the Phase 3 integrated safety
analysis.1,2,4,5 Additionally, the rates of events of
special interest were generally comparable between the RINVOQ and
HUMIRA groups.1,2,4,5 Higher rates of herpes zoster,
lymphopenia, hepatic disorder and blood creatine phosphokinase
(CPK) increase were reported among the RINVOQ
group.1,2,4,5 The majority of herpes zoster and hepatic
disorder cases were non-serious.1 Patients with blood
CPK increase were usually asymptomatic and no cases of
rhabdomyolysis were reported.1 Serious adverse events
occurred at 10.9 events per 100 patient years (100PY) for RINVOQ
compared to 14.1 events/100PY for HUMIRA.1 The rate of
serious infections was 3.0 events/100PY on RINVOQ and 3.5
events/100PY on HUMIRA.1 The rate of deaths was
0.6/100PY on RINVOQ and 0.9/100PY on HUMIRA, including
non-treatment emergent deaths.1 The rate of major
adverse cardiac events (MACE) on both RINVOQ and HUMIRA was
0.4/100PY.1 The rate of venous thromboembolic events
(VTE) was 0.3/100PY on RINVOQ and 0.5/100PY on HUMIRA.1
The rate of malignancy (excluding non-melanoma skin cancer) was
0.6/100PY on RINVOQ and 0.7/100PY on HUMIRA.1
AbbVie previously announced top-line data from
SELECT-COMPARE showing that RINVOQ 15 mg met the primary
endpoints of ACR20 response and clinical remission versus placebo,
as well as all ranked secondary endpoints versus placebo or HUMIRA
at week 12.6 These results were also published in
Arthritis and Rheumatology.
Integrated Safety Analysis up to 4.5 Years
An integrated safety analysis including safety data across
RINVOQ rheumatoid arthritis studies showed that the safety profile
of RINVOQ 15 mg was consistent with previous analyses, with no new
safety risks identified up to 4.5 years of treatment.2,4
This analysis included data pooled from six rheumatoid arthritis
Phase 3 clinical trials and included more than 3,000 patients with
over 7,000 PY of exposure of RINVOQ 15 mg, as well as data of
HUMIRA and MTX.2 In this integrated safety
analysis, results showed that the safety profiles of RINVOQ 15 mg
and HUMIRA were generally similar, with the exception of higher
rates of herpes zoster and blood CPK increase seen with RINVOQ 15
mg.2 Most herpes zoster cases were non-serious (94
percent) and CPK elevations were mostly asymptomatic.2
The most common adverse events seen with RINVOQ 15 mg were upper
respiratory tract infection, nasopharyngitis and urinary tract
infection.2 Rates of serious infections, malignancy
(excluding non-melanoma skin cancer), MACE and VTE were broadly
similar across RINVOQ and comparator-treatment groups.2
The rate of deaths in RINVOQ-treated patients with rheumatoid
arthritis remains consistent with the background rate for patients
with rheumatoid arthritis.2,7-9
"In SELECT-COMPARE, more than a quarter of patients achieved
clinical remission at three years, and the separate integrated
safety analysis showed a consistent safety profile for more than
four years," said Roy M.
Fleischmann, M.D., primary investigator for SELECT-COMPARE
and clinical professor at the University of
Texas Southwestern Medical Center at Dallas. "In a disease
where more than 70 percent of people fail to achieve clinical
remission at all, it is encouraging to see efficacy results coupled
with a consistent safety profile over this period of time."
About Rheumatoid Arthritis
Rheumatoid arthritis is a chronic and debilitating
immune-mediated inflammatory disease that affects an estimated 23.7
million people worldwide.10,11 As the most common form
of autoimmune arthritis, it causes pain, stiffness, swelling and
loss of function in the joints.10,12 Many patients with
rheumatoid arthritis still do not achieve clinical remission or low
disease activity targets.13
About SELECT-COMPARE1,14
SELECT-COMPARE is a Phase 3, multicenter, randomized,
double-blind study designed to evaluate the safety and efficacy of
RINVOQ compared to placebo and HUMIRA in adult patients with
moderate to severe active rheumatoid arthritis who had an
inadequate response to MTX and continued a stable background
of MTX. Patients received background MTX and were randomized 2:2:1
to receive RINVOQ (15 mg, once daily), placebo or HUMIRA (given as
a subcutaneous injection of 40 mg every other week).
The primary endpoints included the percentage of subjects
achieving ACR20 and clinical remission (based on DAS28-CRP) after
12 weeks of treatment compared to placebo. Ranked secondary
endpoints included change in the mTSS compared to placebo and a
comparison versus HUMIRA in percentage of subjects achieving ACR50,
low disease activity, changes in pain as measured by the Patient's
Assessment of Pain (based on VAS) and changes in physical function,
as measured by the Health Assessment Questionnaire-Disability-Index
(HAQ-DI). The trial is ongoing and included a 48-week randomized,
double-blind treatment period followed by an ongoing long-term
extension study for an overall study length of up to ten years.
More information on this trial can be found at
www.clinicaltrials.gov (NCT02629159).
About the Integrated Safety Analysis2
The integrated safety analysis included pooled data from six
randomized, controlled RINVOQ rheumatoid arthritis clinical trials.
Treatment-emergent adverse events, including adverse events of
special interest were summarized for RINVOQ 15 mg (pooled),
upadacitinib 30 mg (pooled), MTX and HUMIRA. Treatment-emergent
adverse events were reported as exposure adjusted event rates
(events/100 PY), which included both incident and recurrent events,
up to a cut-off date of June
2020.
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.3,15-21 In human cellular
assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3
with functional selectivity over cytokine receptors that signal via
pairs of JAK2.3 In August
2019, RINVOQ received U.S. FDA approval for adult patients
with moderately to severely active rheumatoid arthritis who have
had an inadequate response or intolerance to methotrexate. RINVOQ
is approved by the European Commission 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); 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; and for the treatment of active ankylosing spondylitis
(AS) in adult patients who have responded inadequately to
conventional therapy. The approved dose for RINVOQ is 15 mg. Phase
3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis,
Crohn's disease, ulcerative colitis, giant cell arteritis and
Takayasu arteritis are ongoing.16-21
Important Safety Information about
RINVOQ® (upadacitinib)3
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 ≥65 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. The risk of herpes zoster appears to
be higher in Japanese patients treated with upadacitinib. 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 were upper
respiratory tract infections, bronchitis, nausea, blood creatine
phosphokinase (CPK) increased and cough. 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
Union22
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 Information about
HUMIRA® (adalimumab)
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, including hepatitis B reactivation, 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.
About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving
care for people living 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.
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 its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @abbvie on Twitter,
Facebook, Instagram, YouTube and LinkedIn.
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, including the impact of the COVID-19 pandemic on
AbbVie's operations, results and financial results, 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 of
the Allergan acquisition, failure to promptly and effectively
integrate Allergan's businesses, significant transaction costs
and/or unknown or inestimable liabilities, potential litigation
associated with the Allergan acquisition, challenges to
intellectual property, competition from other products,
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 2020 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission (SEC). 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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