CAMEO: Canadian Methotrexate and Etanercept Outcome Study

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean change in DAS28 scores from Month 6 to Month 12 was multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity.

Time frame: Month 6 (randomization) and Month 12

Population: The per protocol population defined as all randomized participants with DAS28 measurements both at the 6- and 12-month visit.

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean changes in DAS28 scores from Baseline were multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity. End of study is Month 24 or early termination.

Time frame: Baseline and Month 6, 12, 18 and 24

Population: Intent to treat; LOCF. The number of participants with available data at Month 6 was 95 and 105 in each treatment group respectively.

X-rays of hands and feet were read centrally and in a blinded manner. Sixteen joints on each hand/wrist and 6 joints on each foot were scored for erosions on a scale of 0 to 5 (or for the feet from 0 to 10, with each side of the joint independently scored from 0 to 5) according to the following: One point is scored if erosions are discrete, rising to 2, 3, 4, or 5 depending on the amount of surface area affected (complete collapse of the bone is scored as 5). Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion) to 280 (worst). A large increase in erosion score is indicative of worsening, whereas a small change or no change is indicative of inhibition of joint erosion. End of study is Month 24 or early termination.

Time frame: Baseline, Month 12 and Month 24

Population: Radiographic Analysis Set - All randomized participants with a Baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

X-rays of hands and feet were read centrally and in a blinded manner. Joint space narrowing (JSN) scores were recorded for each hand/wrist (15 joints) and each foot (6 joints) on a 5-point scale scored as follows: 0 = normal; 1 = focal or doubtful; 2 = generalised, less than 50% of the original joint space; 3 = generalised, more than 50% of the original joint space or subluxation; 4 = bony ankylosis or complete luxation. The scores were summed to calculate the total JSN score ranging from 0 to 168 (worst). A large increase in joint narrowing score is indicative of worsening, whereas a small change or no change is indicative of inhibition of JSN. End of study is Month 24 or early termination.

Time frame: Baseline, Month 12 and Month 24

Population: Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

The modified Total Sharp Score (mTSS) is a measure of change in joint health. X-rays of hands and feet were scored in a blinded manner by an independent reader. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (bony ankylosis or complete luxation). Erosion scores and narrowing scores were added to obtain the total mTSS score, ranging from 0 (normal) to 448 (maximal disease). An increase in mTSS from Baseline (represented by a positive change from Baseline score) indicates disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease (negative change from Baseline score) represents improvement. End of study is Month 24 or early termination.

Time frame: Baseline, Month 12 and Month 24

Population: Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

The HAQ disability index is a patient-reported questionnaire specific for rheumatoid arthritis that addresses health-related quality of life. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (score=0) to 'unable to do' (score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change score indicates an improvement. End of study is Month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat analysis set; LOCF

The HAQ pain visual analog scale (VAS) is a measure of pain on a continuous 100 point scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 (severe pain). End of study is Month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat analysis set with available data; LOCF

The SF-36 assesses the general quality of life (QOL) of participants by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant. The SF-36 is split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. End of study is month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat analysis set with available SF-36 data at month 6; LOCF

The Treatment Satisfaction Questionnaire for Medication is a 14-item self-administered questionnaire which measures patients' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. Optional responses are: Extremely Dissatisfied (1), Very Dissatisfied (2), Dissatisfied (3), Somewhat Satisfied (4), Satisfied (5), Very Satisfied (6), and Extremely Satisfied (7). For each dimension, responses are added and transformed to a scale from 0 - 100, where higher scores indicate greater satisfaction. Change from Month 6 is reported for each dimension; a positive change score indicates improvement. End of study is Month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat analysis set with available data; LOCF. n indicates the number of participants with available data at each time point.

This 6-item assessment measures productivity losses during the past 7 days and includes measures on work time missed due to health, impairment while working due to health (the participant's assessment of the degree to which health affected their productivity while working), overall work impairment due to health (takes into account both hours missed due to health and the participant's assessment of the degree to which health affected their productivity while working) and activity impairment due to health (the degree in which health problems affected their ability to do regular daily activities). Scores for each measure are expressed from 0 to 100 with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. For each measure change from Month 6 is reported; a negative change score indicates improvement. End of study is month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat analysis set with available data; Work time missed and work impairment scores are only calculated for participants who were employed at the time. LOCF imputation was used.

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. Remission is defined by a DAS28 score less than 2.6. Low disease activity is defined by a DAS28 score less than or equal to 3.2. Moderate is defined as a DAS28 higher than 3.2 but lower than or equal to 5.1. DAS28 above 5.1 indicates high disease activity. End of study is Month 24 or early termination.

Time frame: Month 6, 12, 18 and 24

Population: Intent to treat population (all randomized participants); Last observation carried forward (LOCF) imputation was used. At Month 6 data were available for 95 and 105 participants in each treatment group respectively.

Drug persistence is defined as the percentage of participants receiving etanercept at 6, 12, 18, and 24 months.

Time frame: Month 6, 12, 18 and 24

Population: Intent to Treat Analysis Set

A serious adverse event (SAE) is defined by regulatory authorities as one that: • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard.

Time frame: 25 months

Population: Safety Analysis Set