New Long-Term HUMIRA(R) (adalimumab) Data Show Up to Seven-Year Efficacy with Combination Treatment for Rheumatoid Arthritis
2008年6月13日 - 3:00PM
PRニュース・ワイアー (英語)
PARIS, June 13 /PRNewswire-FirstCall/ -- Seven-year rheumatoid
arthritis (RA) data from open-label extension studies show that
treatment with Abbott's HUMIRA(R) (adalimumab) resulted in clinical
remission among long-standing RA patients when used in combination
with methotrexate (MTX). The percentage of patients achieving
clinical remission continued to increase after two or more years of
continuous treatment with combination therapy. These data were
presented at the European League Against Rheumatism (EULAR) annual
meeting in Paris. The seven-year HUMIRA data are a combined
analysis of open-label extensions of the ARMADA, DE019, STAR, DE005
and DE037 trials. The open-label extension period of these studies
assessed the measures of efficacy, remission and change over time
in the safety profile in patients with long-standing RA treated for
up to seven years with 40mg of HUMIRA every other week plus MTX.
"Rheumatoid arthritis is a chronic, progressive disease with no
cure and usually requires long-term management for patients, so it
is reassuring that HUMIRA has demonstrated up to seven years of
efficacy in patients with this disease," said Michael E. Weinblatt,
M.D., Brigham and Women's Hospital, Boston, and lead investigator.
Seven-Year Clinical Data Summary A total of 1,469 patients with a
history of RA who had continued on from randomized, controlled
HUMIRA trials were treated with HUMIRA and MTX for greater than or
equal to 30 days and up to seven years in open-label extension
studies. The average length of exposure to treatment was 47 months.
The randomized controlled HUMIRA study included: * The ARMADA
trial: a Phase III study to evaluate efficacy and safety of HUMIRA
in patients with moderate to severe RA who had failed at least one
disease-modifying anti-rheumatic drug (DMARD). * DE019: a Phase III
study, which evaluated the efficacy and safety of HUMIRA in
patients with moderate to severe RA with inadequate response to
MTX, including assessment of inhibition of radiographic
progression. * The STAR trial: a Phase III study that evaluated the
efficacy and safety of HUMIRA when added to a standard treatment
regimen for RA in patients with inadequate response. * DE005: a
Phase I study evaluating the safety and efficacy of HUMIRA in
combination with methotrexate in methotrexate partial responders. *
DE037: a Phase I roll-over study that evaluated the safety,
pharmacokinetics and early signs of HUMIRA efficacy among RA
patients in the United States and Japan. Efficacy * After six
months of therapy, all efficacy measures showed significant
improvements versus baseline. * At year two, additional
improvements were observed in American College of Rheumatology
(ACR) responses. ACR responses represent a percent improvement in
tender joint count, swollen joint count and other relevant clinical
measures. * Improved response after year one was confirmed by
examining sustained clinical remission (Disease Activity Score
(DAS28) of less than 2.6) for at least three consecutive visits;
sustained remission was achieved in 42 percent of all patients
after a mean of 18 +/- 17 months. DAS28 is a composite index that
includes variables such as the number of tender and swollen joints,
specific laboratory values and other measures of disease activity.
Safety * The treatment exposure-adjusted rate of serious adverse
events (SAEs), and serious infections, declined progressively
during seven years of observation. * Rates and types of SAEs were
consistent with randomized controlled trials, including the rate of
serious infections. Two patients reported tuberculosis, one after
three months and another after 13 months of exposure. About
Rheumatoid Arthritis Unlike osteoarthritis, the most common form of
arthritis, RA is an autoimmune disease where joints are inflamed,
which may lead to damage of the joints' interior and the
surrounding bone. The joints most commonly affected during the
beginning of the disease are the smaller joints of the fingers,
feet and wrists. The elbows, knees, ankles and hips can be
affected, but less often. Although there is no cure for RA, people
continue to seek treatments that not only alleviate the pain and
inflammation but also slow disease progression, thereby inhibiting
the joint damage that can hinder patients from performing daily
activities. Five million people worldwide are currently living with
RA and most of them are between the ages of 25 and 55. Important
Safety Information Globally, prescribing information varies; refer
to the individual country product label for complete information.
Serious infections, sepsis, rare cases of tuberculosis (TB), and
opportunistic infections, including fatalities, have been reported
with the use of TNF antagonists, including HUMIRA. Many of the
serious infections have occurred in patients on concomitant
immunosuppressive therapy that, in addition to their underlying
disease could predispose them to infections. Patients must be
monitored closely for infections, including tuberculosis, before,
during and after treatment with HUMIRA. Treatment should not be
initiated in patients with active infections until infections are
controlled. HUMIRA should not be used by patients with active TB or
other severe infections such as sepsis and opportunistic
infections. Patients who develop new infections while using HUMIRA
should be monitored closely. HUMIRA should be discontinued if a
patient develops a new serious infection until infections are
controlled. Physicians should exercise caution when considering use
of HUMIRA in patients with a history of recurring infection or with
underlying conditions that may predispose patients to infections.
TNF-blocking agents have been associated with reactivation of
hepatitis B (HBV) in patients who are chronic carriers of the
virus. Some cases have been fatal. Patients at risk for HBV
infection should be evaluated for prior evidence of HBV infection
before initiating HUMIRA. The combinations of HUMIRA and anakinra
as well as HUMIRA and abatacept is not recommended. TNF
antagonists, including HUMIRA, have been associated in rare cases
with demyelinating disease and serious allergic reactions. Rare
reports of pancytopenia including aplastic anemia have been
reported with TNF-blocking agents. Adverse events of the
haematologic system, including medically significant cytopenia have
been infrequently reported with HUMIRA. More cases of malignancies
including lymphoma have been observed among patients receiving a
TNF antagonist compared with control patients in clinical trials.
The size of the control group and limited duration of the
controlled portions of studies precludes the ability to draw firm
conclusions. Furthermore, there is an increased background lymphoma
risk in rheumatoid arthritis patients with long-standing, highly
active, inflammatory disease, which complicates the risk
estimation. During the long-term open-label trials with HUMIRA, the
overall rate of malignancies was similar to what would be expected
for an age, gender and race matched general population. With the
current knowledge, a possible risk for the development of lymphomas
or other malignancies in patients treated with a TNF antagonist
cannot be excluded. All patients, and in particular patients with a
medical history of extensive immunosuppressant therapy or psoriasis
patients with a history of Psoralen Ultra-Violet A (PUVA)
treatment, should be examined for the presence of non- melanoma
skin cancer prior to and during treatment with HUMIRA. In clinical
studies with another TNF antagonist, a higher rate of serious
congestive heart failure (CHF) related adverse events including
worsening CHF and new onset CHF have been reported. Cases of
worsening CHF have also been reported in patients receiving HUMIRA.
Physicians should exercise caution when using HUMIRA in patients
who have heart failure and monitor them carefully. HUMIRA should
not be used in patients with moderate or severe heart failure. The
most frequently reported adverse event (greater than or equal to
1/10 patients) at least possibly causally related to HUMIRA is
injection site reaction (including pain, swelling, redness or
pruritus). Other common adverse events (reported by greater than or
equal to >1/100 patients) at least possibly causally related to
HUMIRA include lower respiratory infections (including pneumonia,
bronchitis), viral infections (including influenza, herpes
infections), candidiasis, bacterial infection (including urinary
tract infections), upper respiratory infection, dizziness
(including vertigo), headache, neurologic sensation disorders
(including paraesthesias), cough, nasopharyngeal pain, diarrhea,
abdominal pain, stomatitis and mouth ulceration, nausea, hepatic
enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia,
fatigue (including asthenia and malaise). About HUMIRA HUMIRA is
the only fully human monoclonal antibody approved for the treatment
of rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque
psoriasis, ankylosing spondylitis (AS) and Crohn's disease in the
United States and Europe. HUMIRA resembles antibodies normally
found in the body. It works by blocking tumor necrosis factor alpha
(TNF-alpha), a protein that, when produced in excess, plays a
central role in the inflammatory responses of many immune-mediated
diseases. To date, HUMIRA has been approved in 75 countries and
more than 250,000 people worldwide are currently being treated with
HUMIRA. Clinical trials are also under way evaluating the potential
of HUMIRA in ulcerative colitis. In Europe, 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. HUMIRA is also indicated for the
treatment of severe, active and progressive rheumatoid arthritis in
adults not previously treated with methotrexate. HUMIRA can be
given as monotherapy in case of intolerance to methotrexate or when
continued treatment with methotrexate is inappropriate. HUMIRA has
been shown to reduce the rate of progression of joint damage as
measured by X-ray and to improve physical function, when given in
combination with methotrexate. In the United States, HUMIRA is also
approved for the treatment of juvenile idiopathic arthritis (JIA).
HUMIRA is indicated for the treatment of active and progressive
psoriatic arthritis in adults when the response to previous
disease-modifying anti- rheumatic drug therapy has been inadequate.
HUMIRA has been shown to reduce the rate of progression of
peripheral joint damage as measured by X-ray in patients with
polyarticular symmetrical subtypes of the disease and to improve
physical function. HUMIRA is indicated for the treatment of adults
with severe, active ankylosing spondylitis who have had an
inadequate response to conventional therapy. HUMIRA is indicated
for treatment of severe, active Crohn's disease, in patients who
have not responded despite a full and adequate course of therapy
with a corticosteroid and/or an immunosuppressant; or who are
intolerant to or have medical contraindications for such therapies.
For induction treatment, HUMIRA should be given in combination with
corticosteroids. HUMIRA can be given as monotherapy in case of
intolerance to corticosteroids or when continued treatment with
corticosteroids is inappropriate. HUMIRA is indicated for the
treatment of moderate-to-severe chronic plaque psoriasis in adult
patients who failed to respond to or who have a contraindication
to, or are intolerant to other systemic therapy including
cyclosporine, methotrexate or PUVA. Abbott's Commitment to
Immunology Abbott is focused on the discovery and development of
innovative treatments for immunologic diseases. The Abbott
Bioresearch Center, founded in 1989 in Worcester, Mass., United
States, is a world-class discovery and basic research facility
committed to finding new treatments for autoimmune diseases. About
Abbott Abbott is a global, broad-based health care company devoted
to the discovery, development, manufacture and marketing of
pharmaceuticals and medical products, including nutritionals,
devices and diagnostics. The company employs more than 68,000
people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the
company's Web site at http://www.abbott.com/. DATASOURCE: Abbott
CONTACT: International Media, Ilke Arici, +1-847-938-8551, U.S.
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http://www.abbott.com/
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