Remicade with MTX was first approved for marketing in October 1999 for the treatment of signs and symptoms of RA in patients
who had an inadequate response to MTX.
In patients with RA,joint damage is evident as narrowing of the joint space between bones and erosion of the bones at
the joint space. Remicade inhibits both of these conditions.
"Joint damage progression in RA has two key components,joint space narrowing and joint erosions. Clinical data demonstrates
that Remicade inhibits not only joint erosions but joint space narrowing as well. This provides considerable benefit to patients
while also improving the pain and stiffness associated with the disease,"said Thomas Schable,PhD,senior director,medical affairs,Centocor
Approval was based on 54-week data from the two-year ATTRACT trial (Anti-TNF Trial in RA with Concomitant Therapy),one
of the largest and longer controlled RA clinical trials involving 428 patients at 34 centers in North America and Europe.
In the double blind,placebo-controlled,randomized clinical study,patients treated with Remicade in combination with MTX
were compared to those patients treated with MTX and placebo. MTX is a standard treatment for many patients with RA.
In the ATTRACK trial progression of joint damage was measured radiographically using the van der Heijde modified Sharp
system,which evaluates changes in joint-space narrowing and bone erosion on a 5-point scale(a higher score indicates more
Among all Remicade treatment groups,overall median change from baseline for radiographic scores of 0.0 were reported
among patients treated with the combination of Remicade plus MTX (n=285) compared to a median change of 4.0 for patients treated
with MTX alone (n=63). A total of 53% of Remicade patients demonstrated 0% progression.
The MTX-only findings (control arm) demonstrated progression compareable to that previously reported for patients with
established RA treated with MTX.
Patients on Remicade plus MTX also reported significantly greater relief from the pain and stiffness of the disease as
well as the reduction in the number of swollen and tender joints.
After 54 weeks of therapy,more than half (52%) of those treated with Remicade and MTX experienced a reduction in the
signs and symptoms of RA as measured by ACR 20,a standard assessment for disease activity,compared to 17% of patients
receiving MTX alone.
In the clinical trials,Remicade was generally well tolerated. The most common adverse events included upper respiratory
infection,headache,mild reactions to the infusion,sinusitis,rash,and cough. There was no increased incidence of serious adverse
events or serious infections in patients receiving Remicade and MTX compared to those receiving placebo and MTX.
The incidence of infusion reactions was low in Remicade plus MTX patients (approx, 3%) for any given infusion compared
to those receiving MTX alone (approx. 2%).
TNF-alpha mediates inflammation and cellular immune respose including response to infection. Serious infections,including
sepis and disseminated tuberculosis,have been reported in patients receiving TNF-blocking agents,including Remicade. Some
of these infections have been fatal.
Many of the serious infections in patients treated with Remicade have occurred in patients on concomitant immunosuppressive
therapy that,in addition to their Crohn's disease or RA,could predispose them to infections.
Caution should be exercised when considering the use of Remicade in patients with chronic infection or a history of recurrent
infection. Remicade should not be given to patients with a clinically important,active infection. Patients should be monitored
for signs and symptoms of infection while on or after treatment with Remicade.New infections should be closely monitored.
If a patient develops a serious infection including sepsis. Remicade therapy should be discontinued. Patients should
be evaluated for the risk of tuberculosis,including latent tuberculosis. Treatment for tuberculosis should be initiated prior
to the treatment with Remicade.
Remicade and other agents that inhibit TNF have been associated in rare cases with exacerbation of clinical symptoms
and/or radiographic evidence of de-myelinating disease. Prescribers should exercise caution in considering the use of Remicade
in patients with pre-existing or recent onset of central nervous system de-myelinating disorders.