nd tender joints each and had active RA for at least 6 months prior to baseline. Cimzia was administered subcutaneously in combination with oral MTX for a minimum of 6 months with stable doses of at least 10 mg weekly for 2 months in both trials. There is no experience with Cimzia in combination with DMARDs other than MTX.
Table :2. Clinical trial description
Study number
Patient numbers
Dose regimen
Study objectives
RA-I
(52 weeks)
982
400 mg (0,2,4 weeks) with MTX
200 mg or 400 mg every 2 weeks with MTX
eva luation for treatment of signs and symptoms and inhibition of structural damage.
Co-primary endpoints: ACR 20 at Week 24 and change from baseline in mTSS at Week 52
RA-II
(24 weeks)
619
400 mg (0,2,4 weeks) with MTX
200 mg or 400 mg every 2 weeks with MTX
eva luation for treatment of signs and symptoms and inhibition of structural damage.
Primary endpoint: ACR 20 at Week 24.
mTSS: modified Total Sharp Score
ACR response
The results of clinical trials RA-I and RA-II are shown in Table 3. Statistically significantly greater ACR 20 and ACR 50 responses were achieved from Week 1 and Week 2, respectively, in both clinical trials compared to placebo. Responses were maintained through Weeks 52 (RA-I) and 24 (RA-II). 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. Of these, 427 completed 2 years of open-label follow-up and thus had a total exposure to Cimzia of 148 weeks overall. The observed ACR20 response rate at this timepoint was 91%.The reduction (RA-I) from Baseline in DAS28 (ESR) also was significantly greater (p<0.001) at Week 52 (RA-I) and Week 24 (RA-II) compared to placebo and maintained through 2 years in the open-label extension trial to RA-I.
Table :3. ACR response in clinical trials RA-I and RA-II
Study RA-I
Methotrexate combination
(24 and 52 weeks)
Study RA-II
Methotrexate combination
(24 weeks)
Response
Placebo + MTX
N=199
Cimzia
200 mg + MTX every 2 weeks
N=393
Placebo + MTX
N=127
Cimzia
200 mg + MTX every 2 weeks
N=246
ACR 20
Week 24
14%
59%**
9%
57%**
Week 52
13%
53%**
N/A
N/A
ACR 50
Week 24
8%
37%**
3%
33%**
Week 52
8%
38%**
N/A
N/A
ACR 70
Week 24
3%
21%**
1%
16%*
Week 52
4%
21%**
N/A
N/A
Major Clinical Responsea.
1%
13%**
Cimzia vs. placebo: *p0.01, ** p<0.001
a. Major clinical response is defined as achieving ACR 70 response at every assessment over a continuous 6-month period
Wald p-values are quoted for the comparison of treatments using logistic regression with factors for treatment and region.
Percentage response based upon number of subjects contributing data (n) to that endpoint and time point which may differ from N
Radiographic response
In RA-I, structural joint damage was assessed radiographically and expressed as change in mTSS and its components, the erosion score and joint space narrowing (JSN) score, at Week 52, compared to baseline. Cimzia patients demonstrated significantly less radiographic progression than patients receiving placebo at Week 24 and Week 52 (see Table 4). In the placebo group, 52% of p |
