Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.

DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.

CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.

CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity

CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.

CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity

SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.

0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity

SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.

0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity

Boolean-based definition:

At any time point, a patient must satisfy all of the following:

TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)

Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.

The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status.

A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.

The WPAI yeilds four types of scores:

1. Absenteeism (work time missed)
2. Presenteesism (impairment at work / reduced on-the-job effectiveness)
3. Work productivty loss (overall work impairment / absenteeism plus presenteeism)
4. Activity Impairment WPAI outcomes are expressed as impairment percentages with each subscale score ranging from 0-100. The subscale scores are added and averaged to produce a total WPAI score between 0-100. Higher scores indicate greater impairment and less productivity.

The Sharp-van der Heijde total score ranges from 0-528. Scores for erosion range from 0 to 5 in the hands and 0 to 10 in the feet and reflect erosion size, with 0 defined as no erosion and 3 defined as a large erosion passing the midline of the joint. If there is > 1 erosion per joint, scores can be combined to give a maximum score of 5 per joint in the hands and 10 per joint in the feet (a maximum of 5 at each side of the joint). Joint space narrowing scores vary from 0 to 4 in both the hands and feet, with 0 being normal and 4 being the absence of joint space with evident ankylosis or subluxation. Gross osteolysis and pencil-in-cup change are scored separately and, if present, are assigned the maximum score for erosion and joint space narrowing for the same affected joint. Higher scores indicate increased joint damage.