Clinical Trial Results:
A RANDOMIZED, DOUBLEBLIND PLACEBOCONTROLLED STUDY OF THE MAINTENANCE OF EFFICACY OF ETANERCEPT PLUS DMARD(S) COMPARED WITH DMARD(S) ALONE IN SUBJECTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING AN ADEQUATE RESPONSE WITH ETANERCEPT PLUS DMARD(S).
Summary


EudraCT number 
201100544887 
Trial protocol 
HU CZ 
Global end of trial date 
27 Mar 2015

Results information


Results version number 
v1(current) 
This version publication date 
12 Mar 2016

First version publication date 
12 Mar 2016

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
B1801315


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01578850  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Pfizer, Inc.


Sponsor organisation address 
235 East 42nd Street,, New York, United States, 10017


Public contact 
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800 718 1021, ClinicalTrials.gov_Inquiries@pfizer.com


Scientific contact 
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800 718 1021, ClinicalTrials.gov_Inquiries@pfizer.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
16 Nov 2015


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
04 Mar 2015


Global end of trial reached? 
Yes


Global end of trial date 
27 Mar 2015


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To compare the maintenance of efficacy of the combination of ETN 50 mg once weekly plus MTX (±other DMARDs) therapy with that of MTX (±other DMARDs) at Week 52 in participants with moderately to severely active RA who have achieved LDA (DAS28ESR<3.2) after 24 weeks of therapy with openlabel ETN 50 mg once weekly plus MTX (±other DMARDs) in a treat to target paradigm. An adequate response is defined as a DAS28<3.2 at Week 24.


Protection of trial subjects 
The study was conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences [CIOMS] 2002), Guidelines for GCP (International Conference on Harmonisation [ICH] 1996), and the Declaration of Helsinki (World Medical Association 1996 and 2008).


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
27 Jul 2012


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
South Africa: 30


Country: Number of subjects enrolled 
Taiwan: 24


Country: Number of subjects enrolled 
Thailand: 34


Country: Number of subjects enrolled 
Ukraine: 58


Country: Number of subjects enrolled 
United Arab Emirates: 4


Country: Number of subjects enrolled 
Jordan: 1


Country: Number of subjects enrolled 
Brazil: 18


Country: Number of subjects enrolled 
China: 29


Country: Number of subjects enrolled 
Colombia: 13


Country: Number of subjects enrolled 
Czech Republic: 50


Country: Number of subjects enrolled 
Egypt: 41


Country: Number of subjects enrolled 
Hungary: 5


Country: Number of subjects enrolled 
Lebanon: 1


Country: Number of subjects enrolled 
Malaysia: 13


Country: Number of subjects enrolled 
Mexico: 53


Country: Number of subjects enrolled 
Philippines: 35


Country: Number of subjects enrolled 
Qatar: 2


Country: Number of subjects enrolled 
Romania: 17


Country: Number of subjects enrolled 
Russian Federation: 61


Worldwide total number of subjects 
489


EEA total number of subjects 
72


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
452


From 65 to 84 years 
37


85 years and over 
0



Recruitment


Recruitment details 
The study consisted of Period 1 (an openlabel, 24week treattotarget period), and Period 2 (a doubleblind, randomized, 28week period for participants who qualified for randomization).  
Preassignment


Screening details 
The study was conducted in participants with rheumatoid arthritis (RA) who had moderate to severe disease activity despite methotrexate (MTX) therapy (≥10 mg/week) with or without other nonbiologic disease modifying antirheumatic drugs (DMARDs) for at least 12 weeks prior to screening.  
Period 1


Period 1 title 
Period 1


Is this the baseline period? 
Yes  
Allocation method 
Nonrandomised  controlled


Blinding used 
Not blinded  
Blinding implementation details 
Study medication was not blinded during the openlabel (period 1).


Arms


Arm title

OpenLabel Treatment  
Arm description 
Participants in openlabel treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).  
Arm type 
Experimental  
Investigational medicinal product name 
Etanercept


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Solution for injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants in openlabel treatment received ETN 50 mg QW with MTX (with or without other DMARDs).




Period 2


Period 2 title 
Period 2


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Blinding implementation details 
The method was an electronic process. Blinding codes were only to be broken in emergency situations for reasons of participant safety.


Arms


Are arms mutually exclusive 
No


Arm title

Etanercept  
Arm description 
Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).  
Arm type 
Active comparator  
Investigational medicinal product name 
Etanercept


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Solution for injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).


Arm title

Placebo  
Arm description 
Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs).  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Solution for injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants were randomized to receive PBO 50 mg QW with MTX (with or without other DMARDs).





Baseline characteristics reporting groups


Reporting group title 
OpenLabel Treatment


Reporting group description 
Participants in openlabel treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).  



End points reporting groups


Reporting group title 
OpenLabel Treatment


Reporting group description 
Participants in openlabel treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).  
Reporting group title 
Etanercept


Reporting group description 
Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).  
Reporting group title 
Placebo


Reporting group description 
Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs). 


End point title 
Proportion of participants who remained in Low Disease Activity (LDA) (Disease Activity Score in 28 jointserythrocyte sedimentation rate [DAS28ESR] <3.2) at Week 52.  
End point description 
Proportion of participants who remained in LDA DAS28ESR <3.2 at Week 52 is presented below.


End point type 
Primary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Statistical analysis 1  
Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority ^{[1]}  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in Proportions  
Point estimate 
26.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.78  
upper limit 
35.81  
Notes [1]  Participants who flared in Period 2 are retreated and the data included used in efficacy analyses were carried forward from the last visit before retreatment. 


End point title 
Proportion of participants who remained in Remission at Week 52 (DAS28ESR)  
End point description 
Proportion of participants who remained in Remission (DAS28ESR <2.6) at Week 52.


End point type 
Secondary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Statistical analysis 1  
Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
23.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.83  
upper limit 
40.61 


End point title 
Proportion of participants achieving LDA (DAS28ESR and DAS28Creactive protein [CRP]) at each visit during Period 1  
End point description 
Proportion of participants who achieved LDA (DAS28ESR and DAS28CRP at each visit during period 1 is presented below.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Proportion of participants achieving LDA (DAS28ESR and DAS28CRP) at each visit during Period 2  
End point description 
Proportion of participants who achieved LDA (DAS28ESR and DAS28CRP at each visit during period 2 is presented below.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
DAS28ESR Baseline


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.371  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.76  
upper limit 
0.57  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
DAS28CRP Baseline


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.358  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
1.81  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
DAS28CRP Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.667  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
2.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.76  
upper limit 
9.98  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
DAS28ESR Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
21.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.99  
upper limit 
32.02  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
DAS28CRP Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.81  
upper limit 
29.1  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
DAS28ESR Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
30.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
20.79  
upper limit 
40.83  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
DAS28CRP Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.89  
upper limit 
37.54  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
31.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.51  
upper limit 
41.08  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
DAS28CRP Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
30.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
19.95  
upper limit 
40.47  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
DAS28ESR Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
26.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.78  
upper limit 
35.81  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
DAS28CRP Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.67  
upper limit 
37.47 


End point title 
Proportion of participants achieving remission (DAS28ESR and DAS28CRP) at each visit during Period 1  
End point description 
Proportion of participants who achieved remission (DAS28ESR and DAS28CRP at each visit during period 1 is presented below.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Proportion of participants achieving remission (DAS28ESR and DAS28CRP) at each visit during Period 2  
End point description 
Proportion of participants who achieved LDA (DAS28ESR and DAS28CRP at each visit during period 2 is presented below.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
DAS28CRP Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.774  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.03  
upper limit 
11.68  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
DAS28ESR Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.034  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
12.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.86  
upper limit 
21.69  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
DAS28CRP Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.02  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
16.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.33  
upper limit 
27.54  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
DAS28ESR Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
14.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.48  
upper limit 
23.8  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
DAS28CRP Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
24.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.72  
upper limit 
34.98  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
18.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.16  
upper limit 
27.38  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
DAS28CRP Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
30.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.03  
upper limit 
40.76  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
DAS28ESR Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
20.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.78  
upper limit 
29.52  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
DAS28CRP Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
17.38  
upper limit 
36.93 


End point title 
Change from Baseline in DAS28CRP and DAS28ESR in Period 1  
End point description 
The DAS assessment is a derived measurement with differential weight given to each component. The DAS28ESR and DAS28CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change from Baseline in DAS28CRP and DAS28ESR in Period 2  
End point description 
The DAS assessment is a derived measurement with differential weight given to each component. The DAS28ESR and DAS28CRP was calculated at every visit within the clinical database in period 2. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
DAS28ESR Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
0.2  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
DAS28CRP Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
DAS28ESR Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.68


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.96  
upper limit 
0.39  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
DAS28CRP Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.03  
upper limit 
0.46  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
DAS28CRP Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
0.37  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
DAS28ESR Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.98  
upper limit 
0.4  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
DAS28CRP Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.91  
upper limit 
0.36 


End point title 
Timetoflare during Period 2, based on the protocol criteria  
End point description 
Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28 score during period 2.


End point type 
Secondary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Statistical analysis 1  
Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 


End point title 
Proportion of participants achieving European League Against Rheumatism (EULAR) good and or moderate responses (by both DAS28ESR and DAS28CRP scores) at each visit during Period 1.  
End point description 
EULAR response is based on DAS28ESR scores. The following good and moderate response is defined based on DAS28ESR at endpoint (DAS28ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.61.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Proportion of participants achieving EULAR good and or moderate responses (by both DAS28ESR and DAS28CRP scores) at each visit during Period 2.  
End point description 
EULAR response is based on DAS28ESR scores. The following good and moderate response is defined based on DAS28ESR at endpoint (DAS28ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.61.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Good Response: DAS28CRP Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.961  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.13  
upper limit 
8.9  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Good Response: DAS28ESR Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
21.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.99  
upper limit 
32.02  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Good Response: DAS28CRP Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
18.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.08  
upper limit 
28.53  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Good Response: DAS28ESR Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
31.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.42  
upper limit 
41.39  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Good Response: DAS28CRP Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.83  
upper limit 
37.54  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Good Response: DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
31.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.53  
upper limit 
41.02  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Good Response: DAS28CRP Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
30.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
20.54  
upper limit 
41.05  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Good Response: DAS28ESR Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
26.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.82  
upper limit 
35.74  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Good Response: DAS28CRP Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.63  
upper limit 
37.44  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Good Response: DAS28ESR Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.766  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in Proportions  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.69  
upper limit 
1.65  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Moderate Response: DAS28ESR Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.091  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in Proportions  
Point estimate 
8.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.32  
upper limit 
14.1  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
Moderate Response: DAS28CRP Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.227  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
6.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.28  
upper limit 
11.75  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
Moderate Response: DAS28ESR Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.072  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
9.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.27  
upper limit 
16.6  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
Moderate Response: DAS28CRP Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.108  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
8.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.43  
upper limit 
15.2  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
Moderate Response: DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.035  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
11.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.69  
upper limit 
18.72  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
Moderate Response: DAS28ESR Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.03  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
10.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.2  
upper limit 
17.06  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
Moderate Response: DAS28ESR Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.048  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
11.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.15  
upper limit 
18.06  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
Moderate Response: DAS28CRP Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.016  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
11.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.92  
upper limit 
17.58 


End point title 
Proportion of participants achieving LDA or remission based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at each visit during Period 1.  
End point description 
SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (028) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) in Period 1.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Proportion of participants achieving LDA or remission based on CDAI and SDAI at each visit during Period 2.  
End point description 
SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (028) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) in Period 2.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
CDAI: LDA Baseline


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.358  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
1.81  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
CDAI: LDA: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.341  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
3.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.38  
upper limit 
9.16  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
CDAI: LDA: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
18.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.4  
upper limit 
28.27  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
CDAI: LDA: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
24.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.88  
upper limit 
34.4  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
CDAI: LDA: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.85  
upper limit 
37.35  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
CDAI: LDA: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.61  
upper limit 
34.42  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
CDAI: Remission: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.774  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
2.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.5  
upper limit 
10.06  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
CDAI: Remission: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.645  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.15  
upper limit 
8.03  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
CDAI: Remission: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.08  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
8.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
16.35  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
CDAI: Remission: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.025  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
9.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.49  
upper limit 
17.68  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
CDAI: Remission: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.088  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.02  
upper limit 
16.88  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
SDAI: LDA: Baseline


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.358  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
1.81  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
SDAI: LDA: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.258  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
3.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.57  
upper limit 
10.13  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
SDAI: LDA: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
17.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.49  
upper limit 
27.92  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
SDAI: LDA: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
27.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.93  
upper limit 
37.55  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
SDAI: LDA: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.83  
upper limit 
42.23  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
SDAI: LDA: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
28.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
18  
upper limit 
38.69  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
SDAI: Remission: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.672  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.51  
upper limit 
11.51  
Statistical analysis title 
Statistical analysis 19  
Statistical analysis description 
SDAI: Remission: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.556  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.03  
upper limit 
8  
Statistical analysis title 
Statistical analysis 20  
Statistical analysis description 
SDAI: Remission: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.022  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
10.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.07  
upper limit 
18.45  
Statistical analysis title 
Statistical analysis 21  
Statistical analysis description 
SDAI: Remission: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.047  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
17.25  
Statistical analysis title 
Statistical analysis 22  
Statistical analysis description 
SDAI: Remission: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.031  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
12.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.7  
upper limit 
20.57 


End point title 
Change of CDAI and SDAI at each visit during Period 1.  
End point description 
SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (028) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) in Period 1.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change of CDAI and SDAI at each visit during Period 2  
End point description 
SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (028) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (028) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (010) + Subject Global Assessment of arthritis (010) in Period 2.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
CDAI: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.049  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.19  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
CDAI: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.38


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.72  
upper limit 
1.05  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
CDAI: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.37  
upper limit 
1.67  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
CDAI: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.36  
upper limit 
1.68  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
SDAI: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.047  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.4  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
SDAI: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.97  
upper limit 
1.12  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
SDAI: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.78  
upper limit 
1.88  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
SDAI: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.7  
upper limit 
1.84 


End point title 
Proportion of participants achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 1 at each visit.  
End point description 
A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR’s definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Proportion of participants achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 2 at each visit.  
End point description 
A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR’s definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
ACR 20: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.742  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.21  
upper limit 
3.9  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
ACR 20: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.143  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
9.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.45  
upper limit 
17.06  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
ACR 20: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.111  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
11.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.31  
upper limit 
19.51  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
ACR 20: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.175  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
10.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
18.49  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
ACR 20: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.088  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
10.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.49  
upper limit 
19.05  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
ACR 50: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.584  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
2.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.78  
upper limit 
9.75  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
ACR 50: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.226  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
11.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.59  
upper limit 
21.34  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
ACR 50: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
17.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.76  
upper limit 
27.56  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
ACR 50: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.59  
upper limit 
29.35  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
ACR 50: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in Proportions  
Point estimate 
17.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.3  
upper limit 
28.16  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
ACR 70: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.702  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in Proportions  
Point estimate 
2.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.49  
upper limit 
8.11  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
ACR 70: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.378  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
7.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.37  
upper limit 
17.5  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
ACR 70: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
17.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.12  
upper limit 
27.56  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
ACR 70: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
18.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.4  
upper limit 
28.55  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
ACR 70: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.96  
upper limit 
26.02  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
ACR 90: Week 24


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.921  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.19  
upper limit 
5.67  
Statistical analysis title 
Statistical analysis 17  
Statistical analysis description 
ACR 90: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.41  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
3.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.19  
upper limit 
8.86  
Statistical analysis title 
Statistical analysis 18  
Statistical analysis description 
ACR 90: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.073  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
6.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
12.48  
Statistical analysis title 
Statistical analysis 19  
Statistical analysis description 
ACR 90: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.219  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
4.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.97  
upper limit 
10.08  
Statistical analysis title 
Statistical analysis 20  
Statistical analysis description 
ACR 90: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.196  
Method 
CochranMantelHaenszel  
Parameter type 
Difference in proportions  
Point estimate 
5.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
12.4 


End point title 
Change in the tender and swollen joint counts at each visit during Period 1 (using 28 joint count as well as 66/68 joint counts).  
End point description 
A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in the tender and swollen joint counts at each visit during Period 2 (using 28 joint count as well as 66/68 joint counts).  
End point description 
A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
28 Tender Joint Count: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.062  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.84  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
28 Tender Joint Count: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.015  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.41  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
28 Tender Joint Count: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.72  
upper limit 
0.57  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
28 Tender Joint Count: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.85  
upper limit 
0.66  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
28 Swollen Joint Count: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.68  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
0.5  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
28 Swollen Joint Count: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.437  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.04  
upper limit 
0.45  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
28 Swollen Joint Count: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.131  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.57


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.31  
upper limit 
0.17  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
28 Swollen Joint Count: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.199  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.22  
upper limit 
0.25  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
68 Tender Joint Count: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.115  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.6  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
68 Tender Joint Count: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.017  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.42  
upper limit 
0.35  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
68 Tender Joint Count: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.91  
upper limit 
0.76  
Statistical analysis title 
Statistical analysis 12  
Statistical analysis description 
68 Tender Joint Count: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.19  
upper limit 
0.97  
Statistical analysis title 
Statistical analysis 13  
Statistical analysis description 
68 Swollen Joint Count: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.368  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis 14  
Statistical analysis description 
68 Swollen Joint Count: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.208  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.57


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.46  
upper limit 
0.32  
Statistical analysis title 
Statistical analysis 15  
Statistical analysis description 
68 Swollen Joint Count: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.064  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.84


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.73  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis 16  
Statistical analysis description 
68 Swollen Joint Count: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.081  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.66  
upper limit 
0.1 


End point title 
Change in the Physician Global Assessment of arthritis at each visit during Period 1  
End point description 
The investigator estimated the subject’s overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in the Physician Global Assessment of arthritis at each visit during Period 2  
End point description 
The investigator estimated the subject’s overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.16  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
0.38  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
0.54  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
0.53 


End point title 
Change in the Subject Global Assessment of arthritis in Period 1  
End point description 
Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in the Subject Global Assessment of arthritis in Period 2  
End point description 
Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.048  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.44  
upper limit 
0.43  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
0.33  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
0.31 


End point title 
Change in morning stiffness (measured in minutes) at each visit during Period 1  
End point description 
Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in morning stiffness (measured in minutes) at each visit during Period 2  
End point description 
Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.033  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
14.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
27.07  
upper limit 
1.16  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.013  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
17.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
30.39  
upper limit 
3.68  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
16.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
30.35  
upper limit 
2.73  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
19.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
33.78  
upper limit 
5.54 


End point title 
Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at each visit during Period 1  
End point description 
Participants were asked to answer the question “In general how would you rate your health over the last 2 3 weeks?” by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in the Subject General Health VAS and Pain VAS at each visit during Period 2  
End point description 
Participants were asked to answer the question “In general how would you rate your health over the last 2 3 weeks?” by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
General Health VAS: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.078  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.91  
upper limit 
0.48  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
General Health VAS: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.49  
upper limit 
2.59  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
General Health VAS: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.2  
upper limit 
3.18  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
General Health VAS: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.64  
upper limit 
3.55  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Pain VAS: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.017  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.75  
upper limit 
1.06  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Pain VAS: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.85  
upper limit 
3.34  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Pain VAS: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
9.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.72  
upper limit 
4.26  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Pain VAS: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
9.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.6  
upper limit 
3.99 


End point title 
Change in CRP and ESR at each visit during Period 1  
End point description 
The DAS assessment is a derived measurement with differential weight given to each component. The DAS28ESR and DAS28CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 16 and 24




No statistical analyses for this end point 


End point title 
Change in CRP and ESR at each visit during Period 2  
End point description 
The DAS assessment is a derived measurement with differential weight given to each component. The DAS28ESR and DAS28CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 24, 28, 36, 44 and 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
CRP: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.39  
upper limit 
1.05  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
CRP: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.09  
upper limit 
1.46  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
CRP: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.06  
upper limit 
3.44  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
CRP: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.48  
upper limit 
2.85  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
ESR: Week 28


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.23  
upper limit 
2.49  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
ESR: Week 36


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.33  
upper limit 
5.05  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
ESR: Week 44


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.38  
upper limit 
3.8  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
ESR: Week 52


Comparison groups 
Etanercept v Placebo


Number of subjects included in analysis 
331


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.03  
upper limit 
2.6 


Adverse events information


Timeframe for reporting adverse events 
Adverse events were reported from the signing of the informed consent to 28 days after the last dose of study medication through the last participant's visit.


Adverse event reporting additional description 
The Open Label Safety Population is defined as all participants who had at least one dose of open label study drug during Period 1. The Double Blind Safety Population is defined as all randomized participants who had at least one dose of study drug during period 2.


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
18.0


Reporting groups


Reporting group title 
OpenLabel Treatment


Reporting group description 
Participants in openlabel treatment received ETN 50 mg with MTX (with or without other DMARDs).  
Reporting group title 
Etanercept


Reporting group description 
Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).  
Reporting group title 
Placebo


Reporting group description 
Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs).  


Frequency threshold for reporting nonserious adverse events: 5%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

30 Jan 2012 
In the protocol amendment 1, Clarifications to the details of MTX treatment, MTX supply, and medication errors. Changes to planned analyses: Site 1033 in the crimea was terminated early due to the RussianUkraine conflict. Participant exclusion from the analysis population was described in Section 10.2. 

22 Mar 2013 
In the protocol amendment 2, Clarifications to the Schedule of Activities; QFT testing language; number of sites and countries; definitions of loss of LDA and achieving LDA DAS28 ESR scores; Arm B dosing frequency; language to allow for possible re screenings; contact for breaking the blind; MTX supplies; language for MTX formulation and packaging; personnel performing 66/68 joint assessment; witness consent; reportable information; pregnancy testing language and exposure during pregnancy; laboratory determinations (TB testing was to be handled by a centralized laboratory and hs CRP testing to be done); AE reporting and other reportable information; and publication of study results. Clarifications to inclusion and exclusion criteria. Added a section on the sponsor’s qualified medical personnel and a section on protocol specified SAEs; added occupational exposure to definition of AEs; updated the version of the OMERACT flare questionnaire; added language that MTX was to be considered an IP; added the storage condition of MTX; added language to clarify when liver function tests were not required as a routine procedure; and added language on latex in Appendix 9 of the protocol. 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 