- Three ongoing, randomized, double-blind, multicenter Phase 3
studies demonstrated the long-term efficacy and safety profile of
RINVOQ® (upadacitinib) in treating moderate to severe
atopic dermatitis based on results across 140
weeks1
- Response rates for EASI 75 and vIGA-AD 0/1 (co-primary
endpoints) and for EASI 90 and WP-NRS 0/1 at week 16 were sustained
through week 140 among patients treated with
RINVOQ1
- Safety results were consistent with the known safety profile
of upadacitinib, with no new safety signals
observed1
- Data will be presented as an oral presentation at the 32nd
European Academy of Dermatology and Venereology (EADV)
Congress
NORTH
CHICAGO, Ill., Oct. 11,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced new data analyses from the Measure Up 1, Measure Up 2 and
AD Up Phase 3 studies that further demonstrated the long-term
efficacy and safety profile of RINVOQ® (upadacitinib)
among adults and adolescents 12 years and older with moderate to
severe atopic dermatitis through 140 weeks. Study results will be
orally presented on Wednesday, October
11, at the 32nd European Academy of Dermatology and
Venereology (EADV) Congress in Berlin.
"Patients with moderate to severe atopic dermatitis often face
relentless itch and inflammatory skin symptoms that can impact
their everyday lives," said Mudra Kapoor, M.D., vice president,
global medical affairs, immunology, AbbVie. "These results
reinforce our commitment to providing an effective, long-term
treatment option for those living with this debilitating disease
and other chronic, immune-mediated conditions."
In the Measure Up 1, Measure Up 2 and AD Up Phase 3 studies, a
significantly higher proportion of patients treated with
upadacitinib (15 mg or 30 mg) achieved the co-primary endpoints of
improvement in skin clearance, measured by an EASI score of 75
(EASI 75) and vIGA-AD 0/1 at week 16, compared to those who
received placebo.1 Additionally, more
upadacitinib-treated patients achieved the secondary endpoint of
improvement in skin clearance, measured by an EASI score of 90
(EASI 90), and an additional endpoint of itch reduction (WP-NRS
0/1) at week 16, compared to placebo-treated patients.1
The efficacy of both upadacitinib doses was consistently maintained
for these important measures across all three studies through week
140.1
Week 140 Efficacy
Results (ITT-OC)1,*
|
|
Measure Up
1
|
Measure Up
2
|
AD Up
|
Percent
responders
|
UPA 15 mg
(N=205)
|
UPA 30 mg
(N=206)
|
UPA 15 mg
(N=189)
|
UPA 30 mg
(N=204)
|
UPA 15 mg
(N=200)
|
UPA 30 mg
(N=229)
|
EASI 75
|
88.8
|
90.3
|
82.0
|
90.7
|
81.5
|
90.0
|
vIGA-AD 0/1
|
63.4
|
65.5
|
49.2
|
63.2
|
52.0
|
56.8
|
EASI 90
|
70.7
|
73.8
|
63.5
|
77.5
|
60.0
|
67.2
|
WP-NRS ≥4
|
68.0
(N=200)
|
70.5
(N=207)
|
61.4
(N=184)
|
71.4
(N=199)
|
63.9
(N=191)
|
75.2
(N=222)
|
WP-NRS 0/1
|
46.8
(N=203)
|
50.2
(N=207)
|
43.2
(N=185)
|
52.5
(N=200)
|
43.9
(N=196)
|
50.0
(N=224)
|
* Intent to treat –
observed cases
|
Upadacitinib (15 mg and 30 mg) was generally well tolerated, and
the safety data in the long-term extension of the three studies
were consistent with the known safety profile of upadacitinib, with
no new safety signals observed.1 These results
demonstrated that when taken continuously for a long-term period,
upadacitinib has an acceptable benefit and risk profile for the
treatment of moderate to severe atopic dermatitis.
Long-term Safety
Results1,**
|
|
Measure Up
1
|
Measure Up
2
|
AD Up
|
Events per 100
Patient-Years (E/100 PY)
|
UPA 15 mg
(N=432)
PY=1238.2
|
UPA 30 mg
(N=432)
PY=1270.6
|
UPA 15 mg
(N=431)
PY=1178.6
|
UPA 30 mg
(N=442)
PY=1258.5
|
UPA 15 mg
(N=474)
PY=1295.8
|
UPA 30 mg
(N=472)
PY=1429.9
|
Treatment-Emergent
Adverse Events
|
Any Serious Adverse
Event
|
5.4
|
7.9
|
6.2
|
6.8
|
8.6
|
8.0
|
Treatment-Emergent
Adverse Events of Special Interest
|
Serious
Infections
|
1.9
|
3.4
|
2.3
|
2.5
|
2.5
|
2.2
|
Malignancy
Excluding
Non-Melanoma Skin
Cancer
|
0.3
|
0.5
|
0.2
|
0.4
|
0.5
|
0.4
|
Major Adverse
Cardiovascular
Events (MACE)a,*
|
0.2
|
0
|
<0.1
|
0
|
0.2
|
0.1
|
Venous
Thromboembolic
Events (VTE)b,*
|
0.2
|
0.2
|
0
|
0.3
|
0.2
|
0
|
** Safety analyses
included all patients who received at least 1 dose of study drug.
The data cutoff was
defined as the date when all subjects reached week
140.
|
a MACE
was defined as cardiovascular death, non-fatal myocardial
infarction and non-fatal stroke.
|
b VTE
was defined as deep vein thrombosis and pulmonary
embolism.
|
Additionally, the most common adverse events across all
three studies were COVID-19, upper respiratory tract infection,
acne and nasopharyngitis.1 The full safety data for
these studies will be presented at EADV.
"We are encouraged by these results as they solidify
upadacitinib's potential to improve care for people living with
atopic dermatitis," said Jonathan
Silverberg, M.D., Ph.D., MPH, professor of dermatology and
director of clinical research at the George
Washington University School of Medicine and Health
Sciences. "While upadacitinib has been shown to be an
effective treatment option for patients with atopic dermatitis in
the short term, these data demonstrate a consistent safety profile
and efficacy with long-term treatment."
About Measure Up2
Measure Up 1 and Measure
Up 2 are Phase 3, multicenter, randomized, double-blind,
parallel-group, placebo-controlled studies designed to evaluate the
safety and efficacy of RINVOQ in adult and adolescent (12 years or
older) patients with moderate to severe atopic dermatitis who are
candidates for systemic treatment. Patients were randomized to
RINVOQ 15 mg, RINVOQ 30 mg or placebo. The co-primary endpoints
were the percentage of patients achieving EASI 75 and a validated
Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD)
score of 0/1 after 16 weeks of treatment. Patients receiving
placebo were switched to either RINVOQ 15 mg or RINVOQ 30 mg at
week 16.
About AD Up3
AD Up is a Phase 3,
multicenter, randomized, double-blind, parallel-group,
placebo-controlled study designed to evaluate the safety and
efficacy of RINVOQ in adult and adolescent (12 years or older)
patients with moderate to severe atopic dermatitis who are
candidates for systemic treatment. Patients were randomized to
RINVOQ 15 mg, RINVOQ 30 mg or placebo, all in combination with
topical corticosteroids (TCS). The co-primary endpoints were the
percentage of patients achieving EASI 75 and a vIGA-AD of 0/1 after
16 weeks of treatment. Patients receiving placebo plus TCS were
switched to either RINVOQ 15 mg or RINVOQ 30 mg plus TCS at week
16.
About Atopic Dermatitis
Atopic dermatitis is a
chronic, relapsing inflammatory condition characterized by a cycle
of intense itching and scratching leading to cracked, scaly, oozing
skin.4,5 It affects up to an estimated 10 percent of
adults and 24.6 percent of adolescents.5-7 Between 20
and 46 percent of adults with atopic dermatitis have moderate to
severe disease.8 The range of symptoms poses significant
physical, psychological and economic burden on individuals impacted
by the disease.5,9
About
RINVOQ® (upadacitinib)10
Discovered and developed by AbbVie scientists, RINVOQ is a JAK
inhibitor with seven approved indications and is currently being
studied in several further immune-mediated diseases.10
In human cellular assays, RINVOQ preferentially inhibits signaling
by JAK1 or JAK1/3 with functional selectivity over cytokine
receptors that signal via pairs of JAK2.10
EU Indications and Important Safety Information about
RINVOQ® (upadacitinib)10
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, randomized 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 anti-inflammatory 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
AbbVie's mission is to discover and
deliver innovative medicines and solutions 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,
and eye care – and products and services in our Allergan Aesthetics
portfolio. For more information about AbbVie, please visit us at
www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X
(formerly Twitter), and YouTube.
AbbVie 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, 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 2022 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.
References:
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Through 140 Weeks in Adolescents and Adults with Moderate-to-Severe
Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results. 2023
European Academy of Dermatology and Venereology (EADV) Congress.
October 2023.
- Guttman-Yassky E., et al.
Once-daily upadacitinib versus placebo in adolescents and adults
with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure
Up 2): results from two replicate double-blind, randomised
controlled phase 3 trials. Lancet. 2021; 397(10290):
2151-2168. doi:10.1016/S0140-6736(21)00588-2.
- Reich K, Teixeira HD, Bruin-Weller, et al. Safety and efficacy
of upadacitinib in combination with topical corticosteroids in
adolescents and adults with moderate-to-severe atopic dermatitis
(AD Up): results from a randomised, double-blind,
placebo-controlled, phase 3 trial. Lancet. 2021;
397(10290): 2169-2181.
- Nutten S. Atopic Dermatitis: Global Epidemiology and Risk
Factors. Ann Nutr Metab 2015;66(suppl 1):8–16. doi:
10.1159/000370220.
- Weidinger, S., et al. Atopic dermatitis. Nat Rev Dis
Primers 4, 1(2018). doi: 10.1038/s41572-018-0001-z.
- Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and
Safety of Dupilumab in Adolescents With Uncontrolled Moderate to
Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial.
JAMA Dermatol. 2020;156(1):44-56.
doi:10.1001/jamadermatol.2019.3336
- Blauvelt A, Guttman-Yassky E, Paller AS, et al. Long-Term
Efficacy and Safety of Dupilumab in Adolescents with
Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from
a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). Am
J Clin Dermatol. 2022;23(3):365-383.
doi:10.1007/s40257-022-00683-2
- Shrestha S., et al. Burden of Atopic Dermatitis in the United States: Analysis of Healthcare
Claims Data in the Commercial, Medicare, and Medi-Cal Databases.
Adv Ther.
2017;34(8):1989–2006.
- EFA. Atopic Eczema: Itching for Life Report. 2018. Available
at:
https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf.
Accessed on August 28, 2023.
- Abbvie, Ltd. RINVOQ (upadacitinib) [summary of product
characteristics]. Accessed August 28,
2023.
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf
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