NORTH CHICAGO, Ill.,
June 12, 2018 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today presented new patient-reported
outcome data during the Annual European Congress of Rheumatology
(EULAR 2018) in Amsterdam from
three Phase 3 trials evaluating upadacitinib, an investigational,
once-daily oral JAK1-selective inhibitor, in adult patients with
moderate to severe rheumatoid arthritis.1,2,3
Improvements in pain, physical function and morning joint stiffness
were reported after 12 weeks of treatment with upadacitinib (15 mg
and 30 mg, once-daily) in SELECT-NEXT and SELECT-BEYOND and after
14 weeks of treatment in SELECT-MONOTHERAPY.1,2,3
Additionally, improvements were reported in fatigue and work
instability in SELECT-NEXT and patients' physical component of
health-related quality of life in SELECT-NEXT and SELECT-BEYOND at
12 weeks.1,2 Upadacitinib is not approved by
regulatory authorities and its safety and efficacy have not been
established.
AbbVie has previously announced positive top-line results from
SELECT-NEXT, SELECT-BEYOND and
SELECT-MONOTHERAPY.12,13,14
"Across three Phase 3 studies with different patient
populations, patients treated with upadacitinib reported
improvements in physical function, joint pain and morning
stiffness," said Marek Honczarenko,
M.D., Ph.D., vice president, immunology development, AbbVie. "These
results show upadacitinib's potential to address the challenges
rheumatoid arthritis patients face when performing everyday
activities."
Patient-reported outcomes are an important component of
understanding how rheumatoid arthritis patients perceive the
physical, psychological and social impact of their
disease.15 Using patient-reported outcomes to assess
disease activity allows patients to take an active role in their
treatment journey through shared decision making with their
rheumatologists and healthcare team.
"The deterioration and impairment in physical function
associated with rheumatoid arthritis can dramatically impact
patients' quality of life. Patients included in SELECT-NEXT and
SELECT-BEYOND had difficult-to-treat disease resistant to prior
therapies," said Dr. Vibeke Strand,
adjunct clinical professor in the Division of
Immunology/Rheumatology at Stanford
University School of Medicine. "It is particularly
noteworthy to see that improvements in clinical efficacy previously
reported from these studies were also reflected in patient-reported
outcome measures, such as physical function, morning stiffness and
pain."
Physical Function1,2
- In SELECT-NEXT, improvements in physical function, as measured
by the Health Assessment Questionnaire-Disability Index (HAQ-DI)*,
were observed as early as one week after initial treatment with
upadacitinib across both doses. At week 12, 72/68 percent of
patients receiving 15/30 mg of upadacitinib had improvements in
physical function (HAQ-DI) compared with 49 percent of patients
receiving placebo (p<0.05).
- In SELECT-BEYOND, improvements in physical function (HAQ-DI)
were observed as early as two weeks after initial treatment with
upadacitinib across both doses. At week 12, 63/55 percent of
patients receiving 15/30 mg of upadacitinib had improvements in
physical function (HAQ-DI) compared with 37 percent of patients
receiving placebo (p<0.05).
Joint Pain1,2
- In SELECT-NEXT, patients reported reductions in pain, as
measured by the Patient's Assessment of Pain by Visual Analog Scale
(VAS)**, as early as one week after initial treatment with both
doses of upadacitinib. At week 12, 73 percent of patients receiving
either dose of upadacitinib reported a reduction in pain compared
with 44 percent of patients receiving placebo (p<0.05).
- In SELECT-BEYOND, patients also reported reductions in pain as
early as two weeks after initial treatment with both doses of
upadacitinib. At week 12, 74/64 percent of patients receiving 15/30
mg of upadacitinib reported a reduction in pain compared with 46
percent of patients receiving placebo (p<0.05).
Morning Stiffness***1,2
- In SELECT-NEXT, patients receiving upadacitinib reported
reductions in the severity of morning stiffness as early as one
week after initial treatment with both doses of upadacitinib. At
week 12, 76/80 percent of patients receiving 15/30 mg of
upadacitinib reported reductions in the severity of morning joint
stiffness compared to 60 percent of patients receiving placebo
(p<0.05). Additionally, patients treated with both doses of
upadacitinib had a mean reduction of 85 minutes in the duration of
morning stiffness compared to 34 minutes with placebo (p<0.05)
at week 12.
- In SELECT-BEYOND, patients receiving upadacitinib reported
reductions in the severity of morning stiffness as early as one
week after initial treatment with both doses of upadacitinib. At
week 12, 80/72 percent of patients receiving 15/30 mg of
upadacitinib reported reductions in the severity of morning joint
stiffness compared to 56 percent for placebo (p<0.05).
Additionally, patients reported a mean reduction of 81/80 minutes
in duration of morning stiffness among those receiving 15/30 mg of
upadacitinib compared to 15 minutes for placebo (p<0.05) at week
12.
In a third Phase 3 trial, SELECT-MONOTHERAPY, upadacitinib
monotherapy demonstrated improvements in patients' physical
function (HAQ-DI) and health-related quality of life (Short Form 36
Health Survey) as well as reductions in the duration of morning
joint stiffness compared to patients receiving
methotrexate.3 Additionally, upadacitinib treated
patients reported clinically meaningful improvements as early as
week two for physical function, pain and morning stiffness compared
to week eight (physical function) and week four (pain and morning
stiffness) for those treated with methotrexate. Additional
patient-reported outcomes data from SELECT-MONOTHERAPY will be
presented at a future medical meeting and published in a
peer-reviewed publication.3
Safety results from all three SELECT trials have been previously
reported.12-14
About SELECT-NEXT1
SELECT-NEXT is a Phase 3, multicenter, randomized, double-blind,
placebo-controlled study designed to evaluate the safety and
efficacy of two doses (15 mg and 30 mg) of upadacitinib in adult
patients with moderate to severe rheumatoid arthritis who are on a
stable dose of csDMARDs and have had an inadequate response to
csDMARDs. The primary endpoints included the percentage of subjects
achieving an ACR20 response and low disease activity (LDA) after 12
weeks of treatment. Key secondary endpoints included proportion of
patients achieving ACR50 and ACR70 response and clinical remission
at week 12. Patient-reported outcome responses were evaluated in
patients who continued in the five-year extension phase of
SELECT-NEXT comparing upadacitinib (15 mg and 30 mg) and placebo.
Patient-reported outcomes measured included physical function
(Health Assessment Questionnaire Disability Index [HAQ-DI]),
Patient's Global Assessment of Disease Activity (PtGA) by visual
analog scale (VAS), pain by VAS, fatigue by Functional Assessment
of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity
of morning (AM) stiffness, health-related quality of life (QoL) by
Short Form 36 Health Survey (SF-36), and Work Instability Scale for
RA (RA-WIS). More information on this trial can be found
at www.clinicaltrials.gov (NCT02675426).
About SELECT-BEYOND2
SELECT-BEYOND is a Phase 3, multicenter, randomized,
double-blind, placebo-controlled study designed to evaluate the
safety and efficacy of two once-daily doses (15 mg and 30 mg) of
upadacitinib in adult patients with moderate to severe rheumatoid
arthritis who are on a stable dose of conventional synthetic DMARDs
(csDMARDs) and have had an inadequate response or intolerance to
bDMARDs. The primary endpoints included the percentage of subjects
achieving an ACR20 response and low disease activity (LDA) after 12
weeks of treatment. Secondary endpoints included proportion of
patients achieving ACR50 and ACR70 response at week 12. In this
post-hoc analysis, data from SELECT-BEYOND was used to compare
patient-reported outcome responses between upadacitinib (15 mg and
30 mg) and placebo. Patient-reported outcomes included physical
function by Health Assessment Questionnaire Disability Index
(HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA) by
visual analog scale (VAS), pain by VAS, duration and severity of
morning (AM) stiffness, health-related quality of life (QoL) by
Short Form 36 Health Survey (SF-36), and severity of insomnia by
Insomnia Severity Index (ISI). More information on this trial can
be found at www.clinicaltrials.gov (NCT02706847).
About SELECT-MONOTHERAPY3
SELECT-MONOTHERAPY is a Phase 3, multicenter, randomized,
double-blind, parallel-group study designed to evaluate the safety
and efficacy of upadacitinib monotherapy in adult patients with
moderate to severe rheumatoid arthritis and an inadequate response
to a stable dose of methotrexate. Patients were randomized to
switch from methotrexate to upadacitinib monotherapy (15 mg or 30
mg once-daily) or continue on their prior stable dose of
methotrexate in a blinded manner. The primary endpoints of the
first phase included the percentage of subjects achieving an ACR20
response and low disease activity (LDA) after 14 weeks of
treatment. Secondary endpoints included proportion of patients
achieving ACR50, ACR70 and clinical remission at week 14, Health
Assessment Questionnaire Disability Index (HAQ-DI), duration of
morning (AM) stiffness and health-related quality of life (QoL) by
Short Form 36 Health Survey (SF-36). The trial is ongoing and the
second phase is a blinded long-term extension period to evaluate
the long-term safety, tolerability, and efficacy of the two
once-daily doses (15 mg and 30 mg) of upadacitinib monotherapy in
patients who have completed the first phase. More information on
this trial can be found
at www.clinicaltrials.gov (NCT02706951).
About the SELECT Study Program
The robust SELECT Phase 3 rheumatoid arthritis program evaluates
more than 4,000 patients with moderate to severe rheumatoid
arthritis in six studies. The studies include assessments of
efficacy, safety and tolerability across multiple rheumatoid
arthritis patient populations. Key measures of efficacy evaluated
include ACR responses, Disease Activity Score (DAS28-CRP) and
inhibition of radiographic progression. More information on these
trials can be found at www.clinicaltrials.gov (NCT02706847,
NCT03086343, NCT02629159, NCT02706873, NCT02706951,
NCT02675426).
About Upadacitinib
Discovered and developed by AbbVie, upadacitinib is an
investigational oral agent engineered to selectively inhibit JAK1,
which plays an important role in the pathophysiology of
immune-mediated disorders.4,5 Phase 3 trials of
upadacitinib in rheumatoid arthritis, psoriatic arthritis and
Crohn's disease are ongoing and it is also being investigated to
treat ulcerative colitis, ankylosing spondylitis and atopic
dermatitis.6-11
Upadacitinib is an investigational oral agent and is not
approved by regulatory authorities. Safety and efficacy have not
been established.
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 or 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 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, 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 2017 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.
Key Terms
*HAQ-DI: Health Assessment
Questionnaire Disability Index (HAQ-DI) is a patient questionnaire
with questions regarding the patient's illness and how it affects
their daily life activities.
**Pain: Patient's assessment of pain using the visual analog
scale (VAS) determines pain intensity.
***Severity and Duration of Morning stiffness:
Morning stiffness severity and duration is determined by the
Patient's Assessment of Severity and Duration of Morning Stiffness
questionnaire.
References
- Strand, V et al. Upadacitinib Improves Patient-Reported
Outcomes In Patients With Rheumatoid Arthritis And Inadequate
Response To Conventional Synthetic Disease-Modifying Anti-Rheumatic
Drugs: Results From SELECT-NEXT. Annual European Congress of
Rheumatology (EULAR 2018). June 2018.
- Strand, V et al. Upadacitinib In Patients With Active
Rheumatoid Arthritis And Inadequate Response Or Intolerance To
Biological DMARDs: A Phase 3 Randomized, Placebo-Controlled,
Doubleblind Study Of A Selective JAK1 Inhibitor. Annual European
Congress of Rheumatology (EULAR 2018). June 2018.
- Smolen, J et al. Upadacitinib As Monotherapy: A Phase 3
Randomized Controlled Double-Blind Study In Patients With Active
Rheumatoid Arthritis And Inadequate Response To Methotrexate.
Annual European Congress of Rheumatology (EULAR 2018). June
2018.
- Voss, J, et al; Pharmacodynamics Of a Novel Jak1 Selective
Inhibitor In Rat Arthritis and Anemia Models and In Healthy Human
Subjects. [abstract]. Arthritis Rheum 2013;65 Suppl 10 :2374. DOI:
10.1002/art.2013.65.issue-s10.
- Pipeline – Our Science | AbbVie. AbbVie. 2017. Available
at: https://www.abbvie.com/our-science/pipeline.html. Accessed
on March 29, 2018.
- A Study Comparing ABT494 to Placebo in Subjects With Rheumatoid
Arthritis on a Stable Dose of Conventional Synthetic Disease
Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate
Response to csDMARDs Alone (SELECT-NEXT). ClinicalTrials.gov. 2018.
Available at: https://clinicaltrials.gov/ct2/show/NCT02675426.
Accessed on March 29, 2018.
- A Study Comparing Upadacitinib (ABT-494) to Placebo and to
Adalimumab in Participants With Psoriatic Arthritis Who Have an
Inadequate Response to at Least One Non-Biologic Disease Modifying
Anti-Rheumatic Drug (SELECT - PsA 1). ClinicalTrials.gov. 2018.
Available at: https://clinicaltrials.gov/ct2/show/NCT03104400.
Accessed on March 29, 2018.
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled
Study of ABT-494 for the Induction of Symptomatic and Endoscopic
Remission in Subjects With Moderately to Severely Active Crohn's
Disease Who Have Inadequately Responded to or Are Intolerant to
Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2018.
Available at: https://clinicaltrials.gov/ct2/show/NCT02365649.
Accessed on March 29, 2018.
- A Study Evaluating the Safety and Efficacy of Upadacitinib in
Subjects With Active Ankylosing Spondylitis (SELECT Axis 1).
ClinicalTrials.gov. 2018. Available
at: https://clinicaltrials.gov/ct2/show/study/NCT03178487.
Accessed on March 29, 2018.
- A Study to Evaluate the Safety and Efficacy of ABT-494 for
Induction and Maintenance Therapy in Subjects With Moderately to
Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2018.
Available at: https://clinicaltrials.gov/ct2/show/NCT02819635.
Accessed on March 29, 2018.
- Phase 2b AD Dose Ranging Study (40wk) N=160.
ClinicalTrials.gov. 2018. Available
at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed
on March 29, 2018.
- AbbVie. Data on File, ABVRRTI64466.
- AbbVie. Data on File, ABVRRTI64730.
- AbbVie. Data on File, ABVRRTI65458.
- Deshpande, P.R. et al. Patient-reported outcomes: A new era in
clinical research. Perspect Clin Res. 2011 Oct-Dec; 2(4): 137–144.
Accessed on March 8, 2018.
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