To compare the efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with that of methotrexate monotherapy in the treatment of rheumatoid arthritis over 88 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
834
Subcutaneous (SC), 50 mg, once weekly for 88 weeks
Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
Subcutaneous (SC), 25 mg, once weekly from week 36 to week 88.
Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (≤) 3.2 at Week 88
DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joint count (less than \[\<\]20 percent \[%\] missing SJC or PJC was prorated), erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and Patient's General Health Visual Analog Scale (VAS). VAS is a line 0-100 millimeters (mm) in length; ranged from 0 (very well)-100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units equals (=) low disease activity.
Time frame: Week 88
Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 \< 2.6 units = remission.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28, 36
Percentage of Participants Achieving DAS28 Low Disease Activity or Remission
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 \< 2.6 units = remission.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36
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Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
Subcutaneous (SC), once weekly from week 36 to week 88.
Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
Pfizer Investigational Site
Campsie, New South Wales, Australia
Pfizer Investigational Site
Kogarah, New South Wales, Australia
Pfizer Investigational Site
Maroochydore, Queensland, Australia
Pfizer Investigational Site
Daw Park, South Australia, Australia
Pfizer Investigational Site
Heidelberg West, Victoria, Australia
Pfizer Investigational Site
Malvern, Victoria, Australia
Pfizer Investigational Site
Victoria Park, Australia
Pfizer Investigational Site
Vienna, Austria
Pfizer Investigational Site
Brussels, Belgium
Pfizer Investigational Site
Liège, Belgium
...and 71 more locations
The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity measured on a visual analogue scale (VAS) of 100 mm). Change equals (=) Week X observation minus (-) Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88
The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm). Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Time to Loss of Low Disease Activity DAS28 and a Change of ≥ 0.6 Units in the DAS28
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. Low disease activity = DAS28 ≤ 3.2 units. DAS28 \> 3.2 to 5.1 units = moderate to high disease activity.
Time frame: Week 36 up to Week 88
Time to Loss of Low Disease Activity DAS28
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 greater than (\>)3.2 to 5.1 units = moderate to high disease activity.
Time frame: Week 36 up to Week 88
Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88
DAS28 calculated from the number of SJC and PJC using the 28 joints, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 \< 3.2 units = low disease activity. Cumulative proportion calculated as time-averaged Area Under the Curve (AUC) (AUC divided by number of weeks at that time point), with AUC calculated from Week 36 and Week 88.
Time frame: Week 36 up to Week 88
Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36
American College of Rheumatology (ACR), swollen joint count were an assessment of 28 joints. Joints are classified as either swollen or not swollen. If \< 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
Prorated Swollen Joint Count at Week 36
ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If \< 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by number of non-missing swollen joints). Total possible score of swollen joints ranged from 0-28.
Time frame: Week 36
Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If \< 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
Time frame: Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88
Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36
A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
Painful Joint Count at Week 36
A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible score ranged form 0-28.
Time frame: Week 36
Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
Total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
Time frame: Weeks 36 40, 48, 56, 64, 72, 80 and 88
Change From Baseline in the Physician Global Assessment (PGA) at Weeks 4, 8, 12, 20, 28 and 36
PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
PGA Score at Week 36
PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity.
Time frame: Week 36
Change From Week 36 in the PGA Score at Weeks 40, 48, 56, 64, 72, 80 and 88
PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Change From Baseline in Patient's Global Assessment (PtGA) of Arthritis Pain at Weeks 4, 8, 12, 20, 28 and 36
Participants asked to rate their overall arthritis activity by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
PtGA of Arthritis Pain at Week 36
PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity).
Time frame: Week 36
Change From Week 36 in PtGA of Arthritis Pain at Weeks 40, 48, 56, 64, 72, 80, 88
PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
Change From Baseline in Duration of Morning Stiffness at Weeks 4, 8, 12, 20, 28 and 36
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour times \[\*\] 60 min) was recorded. Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
Duration of Morning Stiffness at Week 36
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour \* 60 min) was recorded.
Time frame: Week 36
Change From Week 36 in Duration of Morning Stiffness at Weeks 40, 48, 56, 64, 72, 80, 88
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour \* 60 min) was recorded. Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
Change From Baseline in General Health at Weeks 4, 8, 12, 20, 28 and 36
General Health VAS is a 100 millimeter (mm) line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
General Health at Week 36
General Health VAS is a 100 mm line marked by the participant. Participants are asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad.
Time frame: Week 36
Change From Week 36 in General Health at Weeks 40, 48, 56, 64, 72, 80, 88
General Health VAS is a 100 mm line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80, 88
Change From Baseline in Pain at Weeks 4, 8, 12, 20, 28 and 36
100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Baseline observation.
Time frame: Baseline, Weeks 4, 8, 12, 20, 28 and 36
Pain at Week 36
100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = pain as bad as it could be. Change = Week x observation minus (-) Baseline observation.
Time frame: Week 36
Change From Week 36 in Pain at Weeks 40, 48, 56, 64, 72, 80 and 88
100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Week 36 observation.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Percentage of Participants Achieving an Acceptable State on the Patient Acceptable Symptom State (PASS) at Baseline and Week 36
PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).
Time frame: Baseline, Week 36
Percentage of Participants Achieving an Acceptable State on the PASS at Week 36 and Weeks 64 and 88
PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).
Time frame: Weeks 36, 64 and 88
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good or Moderate Response at Weeks 4, 8, 12, 20, 28 and 36
EULAR Response Criteria: Good response was defined as \>1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of \<=3.2 units. Non responders were participants with improvement of \<0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of \> 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.
Time frame: Weeks 4, 8, 12, 20, 28 and 36
Percentage of Participants Achieving EULAR Good or Moderate Response at Week 36, 40, 48, 56, 64, 72, 80 and 88
EULAR Response Criteria: Good response was defined as \>1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of \<=3.2 units. Non responders were participants with improvement of \<0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of \> 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.
Time frame: Week 36, 40, 48, 56, 64, 72, 80 and 88
Percentage of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 4, 8, 12, 20, 28 and 36
ACR20 response, ≥ 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and = at least 20% improvement in at least 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (ESR).
Time frame: Weeks 4, 8, 12, 20, 28 and 36
Percentage of Participants With an ACR20 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
ACR20 response: ≥ 20% improvement in tender joint count; ≥20% improvement in swollen joint count; and = at least 20% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Percentage of Participants With an ACR50 Response at Weeks 4, 8, 12, 20, 28 and 36
ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 4, 8, 12, 20, 28 and 36
Percentage of Participants With an ACR50 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Percentage of Participants With an ACR70 Response at Weeks 4, 8, 12, 20, 28 and 36
ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 4, 8, 12, 20, 28 and 36
Percentage of Participants With an ACR70 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and C-Reactive Protein CRP.
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Percentage of Participants With an ACR90 Response at Weeks 4, 8, 12, 20, 28 and 36
ACR90 response: ≥ 90% improvement in tender joint count; = ≥90% improvement in swollen joint count; and = at least 90% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 4, 8, 12, 20, 28 and 36
Percentage of Participants With an ACR90 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
ACR90 response: ≥ 90% improvement in tender joint count; = 90% improvement in swollen joint count; and = 90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
Time frame: Weeks 36, 40, 48, 56, 64, 72, 80 and 88
DAS28 at Week 36
The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm).
Time frame: Week 36