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Anti-TNF Golimumab Continues to Show Promise in Phase II Rheumatoid Arthritis Study
June 14, 2007
Golimumab Demonstrated Sustained Improvement in Signs and Symptoms Of
Moderate to Severe Rheumatoid Arthritis With One-Third of Patients
Achieving Disease Remission at One-Year Mark
One-year data show nearly 75 percent of patients with moderate to
severe rheumatoid arthritis (RA) receiving golimumab (CNTO 148) and
methotrexate (MTX) experienced and maintained at least 20 percent
improvement in arthritis symptoms (ACR 20). This was according to
findings from a double-blind, placebo-controlled, dose-ranging Phase II
study presented today at the European League Against Rheumatism (EULAR)
Annual Congress of Rheumatology. The same study also showed that, on
average, more than one-third of these patients achieved disease
remission at one year as evaluated by Disease Activity Score 28.
Golimumab is a fully-human anti-TNF-alpha monoclonal antibody
that targets and neutralizes both the soluble and the membrane-bound
form of TNF-alpha. Developed by Centocor, Inc and Schering-Plough
Corporation (NYSE: SGP), golimumab is being investigated for
administration by both subcutaneous (SC) injection and intravenous (IV)
infusion.
“The maintained therapeutic effect demonstrated by these results is
very promising,” said Iain B. McInnes, FRCP, Ph.D., Professor of
Experimental Medicine at the University of Glasgow; Honorary Consultant
Rheumatologist, Centre for Rheumatic Diseases, Glasgow Royal Infirmary
in Glasgow, United Kingdom, who serves as a lead investigator in a
Phase III study of golimumab. “Physicians treating patients with RA are
always looking for advanced medications that offer sustained efficacy
to keep this serious, life-altering condition in remission.”
Data from the study showed that significantly greater percentages of
patients treated with golimumab plus MTX achieved ACR 20, 50 and 70
responses (marked improvement in arthritis symptoms according to the
American College of Rheumatology scoring criteria) at Week 16 compared
with patients treated with placebo plus MTX group. Adults with active
RA for at least three months' duration despite methotrexate therapy
were randomized to one of five treatment groups: placebo or golimumab
50 or 100 mg every two weeks or every four weeks. All patients received
stable doses of methotrexate of at least 10 mg/week. Moreover, through
week 52, fewer patients discontinued therapy in the combined golimumab
group (21 percent) than in the placebo/infliximab (control) group (40
percent). There was no clear dose response; through week 52, the
reduction in the signs and symptoms of RA observed at week 16 was
maintained for all doses.
“The fact that golimumab maintained its efficacy over the course of a
full year is very encouraging,” said Robert J. Spiegel, M.D., chief
medical officer and senior vice president, Schering-Plough Research
Institute. “Schering-Plough is a leader in bringing forward innovative
therapies, such as Golimumab, to patients, helping physicians alleviate
their suffering. We are committed to further investigating golimumab as
an effective treatment for these patients.”
About the Study
This Phase II, randomized, double-blind,
placebo-controlled, dose-ranging trial involved 172 patients with
active rheumatoid arthritis for at least three months' duration despite
methotrexate therapy. Patients were randomized to one of five treatment
groups and beginning at week 20, patients randomized to the placebo
group received infliximab (3 mg/kg) at weeks 20, 22, 28, 36, and 44.
Patients receiving golimumab continued at their assigned dose (50 or
100 mg) every four weeks from week 20 to week 48.
The Disease Activity Score 28 (DAS28) was developed to
measure the disease activity in patients with Rheumatoid Arthritis and
has been validated for its use in clinical trials in combination with
the EULAR response criteria. DAS 28 measures, the number of swollen
joints and tender joints (assessed using 28-joint counts ),
inflammation and overall disease activity including measurement of
serum C-reactive protein (CRP) levels. The DAS28 provides a number on a
scale from 0 to 10 indicating the current activity of the rheumatoid
arthritis in the patient. A DAS 28 above 5.1 means high disease
activity whereas a DAS28 below 3.2 indicates low disease activity.
Remission is achieved by A DAS28 lower than 2.6 indicates remission has
been achieved
American College of Rheumatology 20 (ACR20) is utilized
to determine improvement in arthritis signs symptoms. ACR20 represents
an improvement of at least 20 percent in tender joint count and swollen
joint count and at least 20 percent improvement in 3 out of the 5 end
points: acute-phase reactant, patient pain assessment, physician global
assessment, patient global assessment, and patient self-addressed
disability. ACR50 and ACR70 represent improvements of 50 and 70
percent.
Golimumab was generally well tolerated in the study
through week 52. Serious adverse events (AEs) reported prior to
crossover at week 20 were eight percent for the combined golimumab
groups compared with six percent for the placebo group. Through week
20, serious adverse events were reported for 8.8% of the subjects in
the combined golimumab plus methotrexate groups and 5.9% in the placebo
plus methotrexate group. Through week 52, at least 1 serious adverse
event was reported for 16.1% of subjects in the combined golimumab plus
methotrexate groups; serious adverse events were reported in three
subjects after cross over to infliximab plus methotrexate. After
crossover from weeks 20 to 52, serious AEs were seven percent in the
combined golimumab groups, compared to 12 percent in the control group.
No deaths, cases of tuberculosis or other opportunistic infections were
reported through 52 weeks, and serious infections were uncommon. The
most common clinically relevant serious AEs through week 52 were
pneumonia (three patients), lung cancer (unrelated, one patient),
cardiac tamponade (one patient), and cardiac failure (one patient). One
patient died from coronary artery disease approximately four months
after completing 52 weeks of the study.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, debilitating
inflammatory disease that causes pain, swelling, stiffness, and loss of
function in the joints. Symptoms of RA include inflammation of the
joints, swelling, difficulty moving, and pain. The most commonly
affected joints are the hands and feet. The joint pain of RA can impact
a patient's ability to perform normal daily activities, limit job
opportunities, and make family and household responsibilities a
challenge. RA afflicts more than 9.7 million people worldwide;
according to the World Health Organization, the incidence of RA in
Europe is expected to increase over the next decade as the population
ages.
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