Rheumatoid Arthritis
Conditions
Keywords
Humira, methotrexate
Brief summary
A study to assess the safety and efficacy of adalimumab administered as a subcutaneous injection in adult Chinese subjects with rheumatoid arthritis and treated with methotrexate
Detailed description
This was a multi-center, Phase 2/3, randomized, double-blind (DB), parallel group, placebo controlled, safety and efficacy study in adult Chinese RA subjects. The duration of the study was approximately 116 weeks. This included a 4-week (28 days) Screening period, a 12-week Double-Blind (DB) period, a 90-week Open-Label (OL) Period, and a 10-week (70 days) Follow-up period. The 70-day Safety Follow-up period was initiated after the last dose of study medication. During the DB period, 302 Chinese subjects with RA and concomitantly treated with MTX were enrolled at 11 clinical sites located throughout China. Subjects were randomly assigned to one of the three treatment groups in a 2:2:1 ratio: 80 mg adalimumab, 40 mg adalimumab, or placebo. From Week 0 to Week 10, subjects received blinded study drug. Subjects who successfully participated and completed Week 12 of the DB portion of the study participated in the OL period. All subjects in the OL period received adalimumab 40 mg. Throughout the study, the study drug was administered subcutaneously (SC) every other week (eow). Subjects that completed the Week 24 visit, prior to the approval of Protocol Amendment 1, had 70 days from the last dose of study drug to re-enter the study. The Investigator confirmed that the subject did not develop any of the exclusion criteria and completed the procedures defined by the OL Screening visit. Results through Week 24 of this study were presented in the regulatory dossier for the marketing authorization application of Humira in China, fulfilling the requirement for clinical data in Chinese patients. However, in order to continue to provide treatment to patients who responded well to adalimumab, subjects had the option to continue in the OL extension of this study until Week 92.
Interventions
BIOLOGICALPlacebo
Placebo administered subcutaneously (SC) every other week (eow) for 12 weeks, followed by adalimumab 40 mg SC eow for 92 weeks.
BIOLOGICALAdalimumab 80 mg
Adalimumab 80 mg administered subcutaneously (SC) every other week (eow) for 12 weeks, followed by adalimumab 40 mg SC eow for 92 weeks.
BIOLOGICALAdalimumab 40 mg
Adalimumab 40 mg administered subcutaneously every other week for 104 weeks
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Met ACR criteria for diagnosis of active rheumatoid arthritis (RA) and have had at both the Screening visit and Week 0 visit at least four swollen joints (out of 66 assessed) and at least six tender joints(out of 68 assessed) * Subjects must have failed prior treatment with one or more disease-modifying antirheumatic drugs (DMARDs) * DMARDs (other than methotrexate \[MTX\]) must have been discontinued for \>= 28 days or at least 5 half-lives, whichever is greater, before the Week 0 visit * Traditional Chinese Medicines must have been discontinued for \>= 28 days before the Week 0 visit * Subjects must have received at least three months of treatment with MTX (minimum 7.5 mg/week) and remained on a stable dose of MTX for \>= 28 days prior to the Screening visit * Glucocorticoids equivalent to \<= 10 mg of prednisone and prednisone equivalent must have remained unchanged for at least 28 days prior to the Week 0 visit * Must have been able and willing to give written informed consent and to comply with the requirements of this study protocol
Exclusion criteria
* A history of, or current, acute inflammatory joint disease of different origin (e.g., mixed connective tissue disease, seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus, fibromyalgia or any arthritide with onset prior to age 16 years * Wheelchair-bound or bedridden * Joint surgery involving joints to be assessed within this study, within two months prior to the Screening visit * Intra-articular, intramuscular or intravenous administration of corticosteroids within 28 days prior to the Screening visit * Prior treatment with any TNF antagonist, including adalimumab * Subject considered by the investigator, for any reason, to be an unsuitable candidate * Female subject who is pregnant or breast-feeding or considering becoming pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period | Week 12 | American College of Rheumatology (ACR) criteria improvement consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-Blind period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. |
| Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 50% (ACR50) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. |
| Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 70% (ACR70) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. |
| Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | Baseline, Week 12 | Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period. |
| Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period. |
| Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period. |
| Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | Baseline, Week 12 | Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state. Week 12 = end of Double-Blind period. |
| Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | Week 12 | American College of Rheumatology (ACR) criteria improvement consisting of 50% or 70% (ACR50/70) reduction in tender or swollen joint counts and 50% or 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-blind period. |
| Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state. |
| Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state. |
| Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period | Baseline, Week 12 | HAQ is a self-reported, subject-oriented outcome measure. The Standard Disability Index of HAQ for a subject is calculated as the mean of the following 8 category scores (range: 0-3): dressing and grooming, rising, eating, walking, hygiene, reach, grip, and activities. The score of each category is calculated as the maximum of the scores for the questions of that category. The Disability Index cannot be computed if the patient does not have scores for at least 6 categories. A decrease in the Disability Index = improvement in disease (0 = no difficulties). Week 12 = end of Double-Blind period. |
| Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | HAQ is a self-reported, subject-oriented outcome measure. The Standard Disability Index of HAQ for a subject is calculated as the mean of the following 8 category scores (range: 0-3): dressing and grooming, rising, eating, walking, hygiene, reach, grip, and activities. The score of each category is calculated as the maximum of the scores for the questions of that category. The Disability Index cannot be computed if the patient does not have scores for at least 6 categories. A decrease in the Disability Index indicates an improvement in disease (0 = no difficulties). |
| Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Baseline, Week 12 | SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status. |
| Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status. |
| Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status. |
| Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92 | Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered subcutaneously (SC) every other week (eow) for 12 weeks, followed by adalimumab 40 mg SC eow for 92 weeks. | 60 |
| Adalimumab 40 mg Adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for 104 weeks. | 121 |
| Adalimumab 80 mg Adalimumab 80 mg administered subcutaneously (SC) every other week (eow) for 12 weeks, followed by adalimumab 40 mg SC eow for 92 weeks. | 121 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| DB Wk 0 Through 12 (Primary D/C Reasons) | Adverse Event | 1 | 2 | 3 |
| DB Wk 0 Through 12 (Primary D/C Reasons) | Lost to Follow-up | 0 | 0 | 1 |
| DB Wk 0 Through 12 (Primary D/C Reasons) | Various | 0 | 0 | 0 |
| DB Wk 0 Through 12 (Primary D/C Reasons) | Withdrawal by Subject | 0 | 0 | 1 |
| OL Wk 24 to End (Primary D/C Reasons) | Adverse Event | 2 | 10 | 11 |
| OL Wk 24 to End (Primary D/C Reasons) | Lost to Follow-up | 1 | 10 | 6 |
| OL Wk 24 to End (Primary D/C Reasons) | Various | 18 | 25 | 22 |
| OL Wk 24 to End (Primary D/C Reasons) | Withdrawal by Subject | 15 | 19 | 25 |
Baseline characteristics
| Characteristic | Placebo | Adalimumab 40 mg | Adalimumab 80 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 6 Participants | 10 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 115 Participants | 111 Participants | 284 Participants |
| Region of Enrollment China | 60 participants | 121 participants | 121 participants | 302 participants |
| Sex: Female, Male Female | 49 Participants | 104 Participants | 101 Participants | 254 Participants |
| Sex: Female, Male Male | 11 Participants | 17 Participants | 20 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 60 | 30 / 121 | 27 / 121 | 84 / 301 |
| serious Total, serious adverse events | 0 / 60 | 0 / 121 | 3 / 121 | 23 / 301 |
Outcome results
Primary
Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period
American College of Rheumatology (ACR) criteria improvement consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-Blind period.
Time frame: Week 12
Population: Intent-to-treat population (ITT): all randomized subjects who received at least 1 dose of study drug during the double-blind portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period | 21 Participants |
| Adalimumab 40 mg | Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period | 69 Participants |
| Adalimumab 80 mg | Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period | 62 Participants |
Comparison: A sample size of 42 subjects in the placebo group and 84 subjects in each of the adalimumab groups was needed to achieve 98% power to detect that the ACR20 response rate in the 80 mg adalimumab group was different from placebo and to achieve 84% power to detect that the 40 mg adalimumab group was different from placebo.p-value: 0.02695% CI: [1.09, 4.39]Cochran-Mantel-Haenszel
Comparison: A sample size of 42 subjects in the placebo group and 84 subjects in each of the adalimumab groups was needed to achieve 98% power to detect that the ACR20 response rate in the 80 mg adalimumab group was different from placebo and to achieve 84% power to detect that the 40 mg adalimumab group was different from placebo.p-value: 0.00495% CI: [1.35, 5.3]Cochran-Mantel-Haenszel
Secondary
Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period
Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state.
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline | 60.5 mm | Standard Deviation 19.19 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -18.7 mm | Standard Deviation 23.96 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -21.1 mm | Standard Deviation 24.55 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -23.3 mm | Standard Deviation 26.25 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -27.1 mm | Standard Deviation 24.34 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -25.4 mm | Standard Deviation 23.46 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -27.4 mm | Standard Deviation 24.86 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -27.0 mm | Standard Deviation 25.81 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -28.0 mm | Standard Deviation 26.54 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -26.4 mm | Standard Deviation 28.14 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -27.8 mm | Standard Deviation 24.71 |
| Placebo | Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -27.1 mm | Standard Deviation 25.41 |
Secondary
Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period
Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state.
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline | 60.7 mm | Standard Deviation 19.61 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -19.0 mm | Standard Deviation 25.18 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -21.0 mm | Standard Deviation 26.19 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -23.6 mm | Standard Deviation 26.88 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -26.3 mm | Standard Deviation 25.79 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -26.6 mm | Standard Deviation 25.13 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -29.8 mm | Standard Deviation 25.32 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -30.5 mm | Standard Deviation 26.02 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -28.7 mm | Standard Deviation 28.38 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -28.7 mm | Standard Deviation 25.98 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -30.5 mm | Standard Deviation 25.62 |
| Placebo | Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -29.6 mm | Standard Deviation 25.04 |
Secondary
Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period
Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state.
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Baseline | 60.1 mm | Standard Deviation 16.4 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -22.8 mm | Standard Deviation 20.67 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -25.5 mm | Standard Deviation 21.27 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -28.3 mm | Standard Deviation 22.17 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -31.3 mm | Standard Deviation 21.15 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -30.7 mm | Standard Deviation 20.88 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -33.6 mm | Standard Deviation 21.03 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -33.5 mm | Standard Deviation 20.58 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -32.6 mm | Standard Deviation 21.86 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -32.6 mm | Standard Deviation 22.26 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -33.8 mm | Standard Deviation 20.99 |
| Placebo | Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -35.0 mm | Standard Deviation 19.02 |
Secondary
Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period
Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period.
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Baseline | 11.2 Joints | Standard Deviation 7.74 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -6.9 Joints | Standard Deviation 8.03 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -7.4 Joints | Standard Deviation 8.87 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -8.3 Joints | Standard Deviation 8.16 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -8.8 Joints | Standard Deviation 7.87 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -9.3 Joints | Standard Deviation 8.62 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -9.3 Joints | Standard Deviation 8.41 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -9.7 Joints | Standard Deviation 8.45 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -9.0 Joints | Standard Deviation 7.95 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -9.2 Joints | Standard Deviation 7.9 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -9.5 Joints | Standard Deviation 7.99 |
| Placebo | Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -9.5 Joints | Standard Deviation 8 |
Secondary
Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period
Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period.
Time frame: Baseline, Week 12
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the double-blind portion of the study), Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | TJC Week 12 | -7.0 Joints | Standard Deviation 12.1 |
| Placebo | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | SJC Week 12 | -4.7 Joints | Standard Deviation 8.7 |
| Adalimumab 40 mg | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | TJC Week 12 | -12.2 Joints | Standard Deviation 14.9 |
| Adalimumab 40 mg | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | SJC Week 12 | -8.6 Joints | Standard Deviation 8.6 |
| Adalimumab 80 mg | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | TJC Week 12 | -8.8 Joints | Standard Deviation 12.6 |
| Adalimumab 80 mg | Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period | SJC Week 12 | -6.4 Joints | Standard Deviation 6.6 |
Secondary
Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period
Sixty-eight or 66 joints or regions (34 or 32 per body side \[hip joints excluded\]) were assessed by pressure and joint manipulation on physical examination for tender joint count (TJC) or swollen joint count (SJC), respectively. Both joint tenderness and swelling were classified as either present (1), absent (0), replaced (9), or no assessment (NA). The Total TJC or SJC was derived as the sum of all 1s evaluated; the range for TJC and SJC were 0 - 68 and 0 - 66, respectively. The higher the joint count, the worse the rheumatoid arthritis. Week 12 = end of Double-Blind period.
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Baseline | 22.8 Joints | Standard Deviation 16.07 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -9.9 Joints | Standard Deviation 13.44 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -12.3 Joints | Standard Deviation 13.08 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -13.4 Joints | Standard Deviation 13.68 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -14.4 Joints | Standard Deviation 14.15 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -16.4 Joints | Standard Deviation 13.54 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -16.5 Joints | Standard Deviation 13.57 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -17.6 Joints | Standard Deviation 14.24 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -17.0 Joints | Standard Deviation 13.99 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -18.0 Joints | Standard Deviation 14.15 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -18.5 Joints | Standard Deviation 15.18 |
| Placebo | Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -18.0 Joints | Standard Deviation 14.23 |
Secondary
Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period
HAQ is a self-reported, subject-oriented outcome measure. The Standard Disability Index of HAQ for a subject is calculated as the mean of the following 8 category scores (range: 0-3): dressing and grooming, rising, eating, walking, hygiene, reach, grip, and activities. The score of each category is calculated as the maximum of the scores for the questions of that category. The Disability Index cannot be computed if the patient does not have scores for at least 6 categories. A decrease in the Disability Index = improvement in disease (0 = no difficulties). Week 12 = end of Double-Blind period.
Time frame: Baseline, Week 12
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the double-blind portion of the study), Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period | -0.3 score on a scale | Standard Deviation 0.7 |
| Adalimumab 40 mg | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period | -0.5 score on a scale | Standard Deviation 0.5 |
| Adalimumab 80 mg | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period | -0.4 score on a scale | Standard Deviation 0.6 |
Secondary
Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period
HAQ is a self-reported, subject-oriented outcome measure. The Standard Disability Index of HAQ for a subject is calculated as the mean of the following 8 category scores (range: 0-3): dressing and grooming, rising, eating, walking, hygiene, reach, grip, and activities. The score of each category is calculated as the maximum of the scores for the questions of that category. The Disability Index cannot be computed if the patient does not have scores for at least 6 categories. A decrease in the Disability Index indicates an improvement in disease (0 = no difficulties).
Time frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Baseline | 1.38 score on a scale | Standard Deviation 0.692 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | -0.42 score on a scale | Standard Deviation 0.575 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 4 (n = 289) | -0.51 score on a scale | Standard Deviation 0.584 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 8 (n = 283) | -0.55 score on a scale | Standard Deviation 0.621 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 12 (n = 279) | -0.61 score on a scale | Standard Deviation 0.62 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | -0.56 score on a scale | Standard Deviation 0.617 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | -0.58 score on a scale | Standard Deviation 0.609 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | -0.60 score on a scale | Standard Deviation 0.622 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | -0.65 score on a scale | Standard Deviation 0.631 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | -0.65 score on a scale | Standard Deviation 0.603 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | -0.63 score on a scale | Standard Deviation 0.59 |
| Placebo | Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | -0.62 score on a scale | Standard Deviation 0.591 |
Secondary
Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period
SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status.
Time frame: Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period). Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Baseline | 36.50 score on a scale | Standard Deviation 10.894 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | 3.74 score on a scale | Standard Deviation 11.494 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 12 (n = 283) | 5.73 score on a scale | Standard Deviation 12.686 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | 5.22 score on a scale | Standard Deviation 11.699 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | 5.51 score on a scale | Standard Deviation 11.268 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | 5.29 score on a scale | Standard Deviation 11.285 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | 5.56 score on a scale | Standard Deviation 10.716 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | 4.75 score on a scale | Standard Deviation 10.825 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | 5.09 score on a scale | Standard Deviation 11.998 |
| Placebo | Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | 4.14 score on a scale | Standard Deviation 11.867 |
Secondary
Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period
SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status.
Time frame: Baseline, Week 12
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Double-Blind portion of the study), Observed cases included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Physical Component Score, Week 12 | 4.2 score on a scale | Standard Deviation 7.1 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Mental Component Score, Week 12 | 3.5 score on a scale | Standard Deviation 11.8 |
| Adalimumab 40 mg | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Physical Component Score, Week 12 | 5.7 score on a scale | Standard Deviation 7.3 |
| Adalimumab 40 mg | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Mental Component Score, Week 12 | 4.9 score on a scale | Standard Deviation 10.7 |
| Adalimumab 80 mg | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Physical Component Score, Week 12 | 4.5 score on a scale | Standard Deviation 7.6 |
| Adalimumab 80 mg | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period | Mental Component Score, Week 12 | 2.5 score on a scale | Standard Deviation 12.1 |
Secondary
Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period
SF-36 (v.2) is a standardized health survey consisting of 36 questions to measure functional health status. The SF-36 score has two components: physical (PCS) and mental (MCS). Summary scores are calculated using the following 8 scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). An increase in SF-36 PCS or MCS indicates improved health status.
Time frame: Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period). Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Baseline | 32.14 score on a scale | Standard Deviation 7.759 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 0 (n = 293) | 5.01 score on a scale | Standard Deviation 7.356 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 12 (n = 283) | 7.15 score on a scale | Standard Deviation 8.225 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 24 (n = 208) | 6.8 score on a scale | Standard Deviation 7.251 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 36 (n = 200) | 7.96 score on a scale | Standard Deviation 7.478 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 48 (n = 183) | 8.17 score on a scale | Standard Deviation 8.046 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 60 (n = 166) | 8.29 score on a scale | Standard Deviation 7.666 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 72 (n = 150) | 7.77 score on a scale | Standard Deviation 8.806 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 84 (n = 137) | 8.38 score on a scale | Standard Deviation 8.182 |
| Placebo | Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period | Week 92 (n = 130) | 8.49 score on a scale | Standard Deviation 8.195 |
Secondary
Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period
Visual analog scale (VAS) was used for the physician's (PhGA) and patient's (PGA) global assessment of disease activity and the patient's assessment of pain. PhGA assessed the patient's current status, PGA assessed status within the last 24 h, and patient's assessment of pain assessed pain status during the last week. All 3 assessments were scored on a 100 mm horizontal scale. The scores range from 0 (no symptoms) to 100 (maximum symptoms); therefore lower VAS scores represent a better disease state. Week 12 = end of Double-Blind period.
Time frame: Baseline, Week 12
Population: Intent-to-Treat (ITT) population (all subjects who received at least 1 dose of study drug during the double-blind period), Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | Pain, Week 12 | -14.9 mm | Standard Deviation 26 |
| Placebo | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PhGA, Week 12 | -20.6 mm | Standard Deviation 19.1 |
| Placebo | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PGA, Week 12 | -13.8 mm | Standard Deviation 26.2 |
| Adalimumab 40 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | Pain, Week 12 | -22.7 mm | Standard Deviation 25.2 |
| Adalimumab 40 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PhGA, Week 12 | -25.1 mm | Standard Deviation 22.7 |
| Adalimumab 40 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PGA, Week 12 | -23.6 mm | Standard Deviation 25.2 |
| Adalimumab 80 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PhGA, Week 12 | -20.9 mm | Standard Deviation 19.7 |
| Adalimumab 80 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | PGA, Week 12 | -16.3 mm | Standard Deviation 25.5 |
| Adalimumab 80 mg | Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period | Pain, Week 12 | -16.4 mm | Standard Deviation 22.4 |
Secondary
Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period
American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 0 Responders (n = 293) | 152 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 4 Responders (n = 289) | 179 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 8 Responders (n = 283) | 183 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 12 Responders (n = 279) | 207 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 24 Responders (n = 208) | 153 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 36 Responders (n = 200) | 158 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 48 Responders (n = 183) | 147 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 60 Responders (n = 166) | 131 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 72 Responders (n = 150) | 108 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 84 Responders (n = 137) | 111 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period | Week 92 Responders (n = 130) | 105 Participants |
Secondary
Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period
American College of Rheumatology (ACR) criteria improvement consisting of 50% or 70% (ACR50/70) reduction in tender or swollen joint counts and 50% or 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-blind period.
Time frame: Week 12
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the double-blind portion of the study), non-responder imputation (NRI; missing ACR responses imputed as non-responders).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR50 | 9 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR70 | 2 Participants |
| Adalimumab 40 mg | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR50 | 39 Participants |
| Adalimumab 40 mg | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR70 | 19 Participants |
| Adalimumab 80 mg | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR50 | 29 Participants |
| Adalimumab 80 mg | Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period | ACR70 | 11 Participants |
p-value: 0.009Cochran-Mantel-Haenszel
p-value: 0.121Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period
American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 50% (ACR50) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 0 Responders (n = 293) | 77 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 4 Responders (n = 289) | 95 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 8 Responders (n = 283) | 103 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 12 Responders (n = 279) | 119 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 24 Responders (n = 208) | 96 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 36 Responders (n = 200) | 102 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 48 Responders (n = 183) | 94 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 60 Responders (n = 166) | 74 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 72 Responders (n = 150) | 79 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 84 Responders (n = 137) | 74 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period | Week 92 Responders (n = 130) | 69 Participants |
Secondary
Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period
American College of Rheumatology (ACR) criteria improvement in a subject's disease condition versus Baseline consisting of 70% (ACR70) reduction in tender or swollen joint counts and 20/50/70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92
Population: Intent-to-Treat (ITT) population (all randomized subjects who received at least 1 dose of study drug during the Open-Label period. Participant numbers are reduced from the Double-Blind period as not all enrolled participants in the DB period also enrolled in the OL period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 0 Responders (n = 293) | 32 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 4 Responders (n = 289) | 39 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 8 Responders (n = 283) | 49 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 12 Responders (n = 279) | 52 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 24 Responders (n = 208) | 39 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 36 Responders (n = 200) | 48 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 48 Responders (n = 183) | 40 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 60 Responders (n = 166) | 37 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 72 Responders (n = 150) | 30 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 84 Responders (n = 137) | 38 Participants |
| Placebo | Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period | Week 92 Responders (n = 130) | 34 Participants |