atients experienced no radiographic progression (mTSS 0.0) at Week 52 compared to 69% in the Cimzia 200 mg treatment group.
Table :4. Changes over 12 months in RA-I
Placebo + MTX
N=199
Mean (SD)
Cimzia 200 mg + MTX
N=393
Mean (SD)
Cimzia 200 mg + MTX –
Placebo + MTX
Mean Difference
mTSS
Week 52
2.8 (7.8)
0.4 (5.7)
-2.4
Erosion Score
Week 52
1.5 (4.3)
0.1 (2.5)
-1.4
JSN Score
Week 52
1.4 (5.0)
0.4 (4.2)
-1.0
p-values were < 0.001 for both mTSS and erosion score and 0.01 for JSN score. An ANCOVA was fitted to the ranked change from baseline for each measure with region and treatment as factors and rank baseline as a covariate.
Of the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of placebo-controlled treatment and entered the open-label extension study. Sustained inhibition of progression of structural damage was demonstrated in a subset of 449 of these patients who completed at least 2 years of treatment with Cimzia (RA-I and open-label extension study) and had eva luable data at the 2-year timepoint.
Physical function response and health-related outcomes
In RA-I and RA-II , Cimzia-treated patients reported significant improvements in physical function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) and in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) from Week 1 through to the end of the studies compared to placebo. In both clinical trials, Cimzia-treated patients reported significantly greater improvements in the SF-36 Physical and Mental Component Summaries and all domain scores. Improvements in physical function and HRQoL were maintained through 2 years in the open-label extension to RA-I. Cimzia-treated patients reported statistically significant improvements in the Work Productivity Survey compared to placebo.
Immunogenicity
The overall percentage of patients with antibodies to Cimzia detectable on at least 1 occasion was 7.7% in the Phase III RA placebo-controlled trials. Approximately one-third of antibody-positive patients (2.6% of the total population) had antibodies with neutralising activity in vitro. Patients treated with concomitant immunosuppressants (MTX) had a lower rate of antibody development than patients not taking immunosuppressants at baseline. Antibody formation was associated with lowered drug plasma concentration and in some patients, reduced efficacy.
A pharmacodynamic model based on the Phase III trial data predicts that around 15% of the patients develop antibodies in 6 months at the recommended dose regimen (200 mg every 2 weeks following a loading dose) without MTX co-treatment. This number decreases with increasing doses of concomitant MTX treatment. These data are reasonably in agreement with observed data.
The data reflect the percentage of patients whose test results were considered positive for antibodies to Cimzia in an ELISA, and are highly dependant on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodies in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medicinal products, and underlying disease. For these reasons, comparison of the incidence of antibodies to Cimzia with the incidence of antibodies to other TNF antagonists is not appropriate.
5.2 Pharmacok |
