First-line therapy with Orencia in
combination with MTX resulted in patients with early RA achieving
significantly higher rates of stringent measures of remission,
including 37 percent of patients achieving Boolean-defined
remission and 42 percent of patients achieving CDAI- and
SDAI-defined remission at 12 months versus patients on MTX alone
(22.4 percent, 27.6 percent, and 25 percent, respectively;
P<0.05 for all three measures)
Analysis showed treatment with Orencia plus
MTX reduced the development of anti-CCP antibodies, an indicator of
more severe, persistent, and erosive disease in patients with early
rapidly progressing RA
Sustained improvements on MRI endpoints were
also observed demonstrating Orencia plus MTX improved synovitis and
osteitis scores at 12 months, and improved joint erosion scores at
both 12 and 18 months, compared to MTX alone
Bristol-Myers Squibb Company (NYSE:BMY) today announced results
of several new sub-analyses of the Phase IIIb AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial that investigated the use
of Orencia plus methotrexate (MTX) in biologic and MTX-naïve
citrullinated protein (CCP)-positive early moderate to severe
rheumatoid arthritis (RA) patients. These data were presented this
week at the American College of Rheumatology (ACR) 2014 annual
meeting.
Orencia is currently indicated in adults for moderate to severe
RA. Orencia should not be administered with tumor necrosis factor
antagonists and should not be used with other biologic RA
drugs.
One of the analyses looked at anti-CCP antibodies, which are a
marker of RA and may contribute to disease progression. The
analysis assessed the development of anti-CCP antibodies in
patients with early rapidly progressing RA by measuring isotypes
(related antibody classes) and the number of epitopes (a specific
area of an antigen to which an antibody binds) recognized after
treatment with Orencia plus MTX, Orencia alone, or MTX alone.
Results demonstrated Orencia plus MTX numerically reduced the
concentrations of all CCP isotypes and the average number of
epitopes recognized over one year of treatment more than Orencia
alone or MTX alone.
“Important results were seen in CCP-positive patients,” said
T.W.J. Huizinga, MD, PhD, Leiden University Medical Center, Leiden
Netherlands. “The results of our analysis demonstrate that patients
who start treatment with a combination of Orencia plus methotrexate
in early rheumatoid arthritis may potentially slow disease
progression.”
Over 12 months of treatment, 6.7 percent, 12.1 percent, and 7.8
percent of patients on Orencia plus MTX, Orencia alone, and MTX
alone, respectively, experienced a serious adverse event and 1.7
percent, 4.3 percent and 2.6 percent led to discontinuation.
Serious infections were observed in 0.8 percent of patients in the
combination arm and 3.4 percent in the Orencia monotherapy arm.
None of the patients in the MTX alone arm experienced a serious
infection. Malignancies were reported in 0.8 percent, 1.7 percent,
and 0 percent of patients in the Orencia + MTX, Orencia, and MTX
arms, respectively.
Additional AVERT Sub-Analyses Findings
Additionally at ACR, investigators presented 12-month efficacy
data from AVERT, including new results assessing the effect of
Orencia on more clinically stringent remission criteria than
DAS-defined (DAS28 CRP <2.6) remission, as well as new MRI
data.
Significantly more patients on Orencia plus MTX achieved the
stringent clinical endpoint of Boolean-defined remission at 12
months (37 percent Orencia plus MTX; 26.7 percent Orencia alone;
22.4 percent MTX alone; P<0.05). Higher remission rates as
compared to MTX or Orencia alone were consistent across other
clinically stringent measures, including CDAI remission (42 percent
Orencia plus MTX; 31 percent Orencia alone; 27.6 percent MTX alone;
P<0.05) and SDAI remission (42 percent Orencia plus MTX; 29.3
percent Orencia alone; 25 percent MTX alone; P<0.05). A small
but significantly higher number of patients treated with Orencia
plus MTX were able to maintain drug-free remission up to month 18
and six months after drug withdrawal, according to the remission
threshold of DAS28-CRP <2.4 (13 percent Orencia plus MTX; vs.
3.5 percent MTX alone; P=0.002).
Sustained improvements on MRI endpoints were also observed at
six months after stopping combination therapy with Orencia plus MTX
vs. MTX alone, including improved measurements of both joint
inflammation and joint erosion. At 18 months of this post-hoc
analysis, the adjusted mean change from baseline in total synovitis
score was -1.34 for Orencia plus MTX vs. -0.49 for MTX alone; -2.03
for Orencia plus MTX vs. 0.34 for MTX alone in total osteitis
score; and 0.13 for Orencia plus MTX vs. 2.00 for MTX alone in
total erosion score (p<0.05 for all three measures).
“The new AVERT findings presented at ACR reinforce Bristol-Myers
Squibb’s commitment to understanding the disease pathology of RA
and the results associated with earlier treatment with a
combination of Orencia plus methotrexate,” said Douglas Manion,
M.D., head of Specialty Development, Bristol-Myers Squibb.
“Collectively, the efficacy, safety and real-world data presented
at ACR will provide clinicians with valuable insights into
treatment response and outcomes in patients with early rheumatoid
arthritis.”
Patient-Reported Outcomes
Orencia plus MTX improved patient-reported outcomes for fatigue,
pain, physical functioning and participation in daily activities
compared to MTX. At 12 months, the Orencia plus MTX treatment arm
reported a significant improvement in fatigue (-34.9) vs. MTX alone
(-26.7; P<0.05); and in health-related quality of life score,
13.9 for Orencia plus MTX vs. 10.9 for MTX alone; (P<0.05).
Recent EULAR recommendations reinforce the need to assess a
treatment’s impact on the patient’s daily activities and overall
quality of life.
About the AVERT Trial
The AVERT trial includes 351 adult patients with symptoms of
moderate to severe RA for less than two years, positive for
anti-CCP antibodies, DAS28 CRP >3.2 and naïve to treatment with
methotrexate and biologic therapies for RA. The patients were
randomly assigned to 12 months of weekly treatment in one of three
groups: Orencia 125 mg subcutaneous plus MTX; Orencia 125 mg
subcutaneous alone; or MTX alone.
Indications/Usage and Important Safety
Information for ORENCIA® (abatacept)
Indications/Usage
Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is
indicated for reducing signs and symptoms, inducing major clinical
response, inhibiting the progression of structural damage, and
improving physical function in adult patients with moderately to
severely active RA. ORENCIA may be used as monotherapy or
concomitantly with disease-modifying, anti-rheumatic drugs (DMARDs)
other than tumor necrosis factor (TNF) antagonists.
Juvenile Idiopathic Arthritis (JIA): ORENCIA is also
indicated for reducing signs and symptoms in pediatric patients
aged 6 years and older with moderately to severely active
polyarticular JIA. ORENCIA may be used as monotherapy or
concomitantly with methotrexate (MTX).
Important Limitations of Use: ORENCIA should not be
administered concomitantly with TNF antagonists, and is not
recommended for use concomitantly with other biologic RA therapy,
such as anakinra.
Important Safety Information
Concomitant Use with TNF Antagonists: Concurrent therapy
with ORENCIA and a biologic DMARD is not recommended. In controlled
clinical trials, adult patients receiving concomitant intravenous
ORENCIA and TNF antagonist therapy experienced more infections
(63%) and serious infections (4.4%) compared to patients treated
with only TNF antagonists (43% and 0.8%, respectively), without an
important enhancement of efficacy.
Hypersensitivity: Anaphylaxis or anaphylactoid reactions
can occur during or after an infusion and can be life-threatening.
In controlled, double-blind and open-label clinical trials,
anaphylaxis and anaphylactoid reactions were reported in <0.1%
of adult patients dosed with intravenous ORENCIA. Other reactions
potentially associated with drug hypersensitivity, such as
hypotension, urticaria, and dyspnea, that occurred within 24 hours
of ORENCIA infusion, were uncommon (<1% each). There was one
case of a hypersensitivity reaction with ORENCIA in JIA clinical
trials (0.5%; n=190). In postmarketing experience, a case of fatal
anaphylaxis following the first infusion of ORENCIA was reported.
Appropriate medical support measures for treating hypersensitivity
reactions should be available for immediate use. If an anaphylactic
or other serious allergic reaction occurs, administration of
ORENCIA should be stopped immediately and permanently discontinued,
with appropriate therapy instituted.
Infections: Serious infections, including sepsis and
pneumonia, have been reported in patients receiving ORENCIA. Some
of these infections have been fatal. Many of the serious infections
have occurred in patients on concomitant immunosuppressive therapy
which in addition to their underlying disease, could further
predispose them to infection. Caution should be exercised in
patients with a history of infection or underlying conditions which
may predispose them to infections. Treatment with ORENCIA
(abatacept) should be discontinued if a patient develops a serious
infection. Patients should be screened for tuberculosis, and viral
hepatitis in accordance with published guidelines, and if positive,
treated according to standard medical practice prior to therapy
with ORENCIA.
Immunizations: Live vaccines should not be given
concurrently with ORENCIA or within 3 months of its discontinuation
as it may blunt the effectiveness of some immunizations. It is
recommended that JIA patients be brought up to date with all
immunizations in agreement with current immunization guidelines
prior to initiating therapy with ORENCIA.
Use in Patients with Chronic Obstructive Pulmonary Disease
(COPD): Adult COPD patients treated with ORENCIA developed
adverse events more frequently than those treated with placebo (97%
vs 88%, respectively). Respiratory disorders occurred more
frequently in patients treated with ORENCIA compared to those on
placebo (43% vs 24%, respectively), including COPD exacerbations,
cough, rhonchi, and dyspnea. A greater percentage of patients
treated with ORENCIA developed a serious adverse event compared to
those on placebo (27% vs 6%), including COPD exacerbation [3 of 37
patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of
ORENCIA in patients with RA and COPD should be undertaken with
caution, and such patients monitored for worsening of their
respiratory status.
Blood Glucose Testing: ORENCIA for intravenous
administration contains maltose, which may result in falsely
elevated blood glucose readings on the day of infusion when using
blood glucose monitors with test strips utilizing glucose
dehydrogenase pyrroloquinolinequinone (GDH-PQQ). Consider using
monitors and advising patients to use monitors that do not react
with maltose, such as those based on glucose dehydrogenase nicotine
adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose
hexokinase test methods. ORENCIA for subcutaneous (SC)
administration does not contain maltose; therefore, patients do not
need to alter their glucose monitoring.
Pregnant and Nursing Mothers: ORENCIA should be used
during pregnancy only if clearly needed. The risk for development
of autoimmune diseases in humans exposed in utero to abatacept has
not been determined. Nursing mothers should be informed of the
risk/benefit of continued breast-feeding or discontinuation of the
drug. A pregnancy registry has been established to monitor fetal
outcomes. Healthcare professionals are encouraged to register
pregnant patients exposed to ORENCIA by calling 1-877-311-8972.
Most Serious Adverse Reactions: Serious infections (3%
ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1%
placebo). In general, adverse events in pediatric and adolescent
patients were similar in frequency and type to those seen in adult
patients.
Malignancies: The overall frequency of malignancies was
similar between adult patients treated with ORENCIA or placebo.
However, more cases of lung cancer were observed in patients
treated with ORENCIA (0.2%) than those on placebo (0%). A higher
rate of lymphoma was seen compared to the general population;
however, patients with RA, particularly those with highly active
disease, are at a higher risk for the development of lymphoma. The
potential role of ORENCIA in the development of malignancies in
humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper
respiratory tract infection, nasopharyngitis, and nausea were the
most commonly reported adverse events in the adult RA clinical
studies.
Note concerning SC ORENCIA: The safety and efficacy of SC
ORENCIA has not been studied in patients under 18 years of age.
Please see Full Prescribing Information.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune
disease characterized by inflammation in the lining of joints (or
synovium), causing joint damage with chronic pain, stiffness, and
swelling. RA causes limited range of motion and decreased joint
function. The condition is more common in women than in men, who
account for 75 percent of patients diagnosed with RA.
About Orencia
Orencia SC and IV is indicated for reducing signs and symptoms,
inducing major clinical response, inhibiting the progression of
structural damage, and improving physical function in adult
patients with moderately to severely active rheumatoid arthritis.
Orencia may be used as monotherapy or concomitantly with
disease-modifying antirheumatic drugs (DMARDs) other than tumor
necrosis factor (TNF) antagonists.
Orencia IV is indicated for reducing signs and symptoms in
pediatric patients 6 years of age and older with moderately to
severely active polyarticular juvenile idiopathic arthritis.
Orencia IV may be used as monotherapy or concomitantly with
methotrexate (MTX). The safety and efficacy of Orencia SC has not
been studied in patients under 18 years of age.
Orencia should not be administered concomitantly with TNF
antagonists.
Orencia is not recommended for use concomitantly with other
biologic rheumatoid arthritis (RA) therapy, such as anakinra.
Orencia is intended for use under the guidance of a physician or
healthcare practitioner.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases.
For more information about Bristol-Myers Squibb, visit
http://www.bms.com, or follow us on Twitter at
http://twitter.com/bmsnews
Orencia is a registered trademark of Bristol-Myers Squibb
Company.
About Bristol-Myers Squibb Immunoscience
The immune system is the body’s natural defense against disease.
These processes come into play in almost every human disease. That
is why Bristol-Myers Squibb is focused on exploring ways to harness
the body’s own immune system to treat immune-related diseases with
high unmet medical needs, including RA – a chronic, systemic,
inflammatory autoimmune disorder that affects the joints.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Forward-looking statements in this press release
should be evaluated together with the many uncertainties that
affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2013 in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
Bristol-Myers SquibbMedia:Chris Clark,
215-421-4887chris.clark@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comorRyan Asay,
609-252-5020ryan.asay@bms.com
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