Comparison of CHS-0214 to Enbrel (Etanercept) in Patients With Rheumatoid Arthritis (RA)

The primary efficacy endpoint in Part 1 was the percentage of subjects who achieved ACR20 (20% improvement according to American College of Rheumatology criteria) at week 24 compared to baseline (last non-missing value prior to first dose). Subjects were considered an ACR20 responder if when compared to baseline (last non-missing value prior to first dose), they achieved a 20% decrease in SJC (Swollen joint count), 20% decrease in TJC (Tender joint count), and 20% improvement in 3 of the following 5 measures: high sensitivity C reactive protein(hs-CRP), Health Assessment Questionnaire Disability Index(HAQ-DI), subjects global assessment of pain(SPA, VAS), subject's global assessment of disease activity(SGA-VAS), physician's global assessment of disease activity(PGA-VAS)

Subjects were considered an ACR20 responder if, when compared to baseline (last non-missing value prior to first dose), they achieved a 20% decrease in SJC, 20% decrease in TJC, and 20% improvement in 3 of the following 5 measures:

• High sensitivity C-reactive protein (hs-CRP);
• Health Assessment Questionnaire-Disability Index (HAQ-DI);
• Subject's global assessment of pain (ie, subject's pain assessment [SPA]-visual analog scale [VAS]);
• Subject's global assessment of disease activity (SGA-VAS); and
• Physician's global assessment of disease activity (PGA-VAS).

In these calculations, the percent change from baseline to endpoint was used to determine ACR20. For percentage change calculations, results were rounded to 5 decimal places prior to comparing to the threshold of 20%.For SJCs and TJCs, the assessment of efficacy was based on mean change from baseline (last non-missing value prior to first dose evaluation).

The average percent improvement from baseline in individual ACR response criteria: TJC (Tender joint count) the 66/68 Joint Count evaluates 68 joints for tenderness and pain with movement. The temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP), hip, knee, ankle, tarsus, metatarsophalangeal (MTP), and interphalangeal of the feet are included in this joint count. Hip joints can be evaluated for tenderness.

The 66/68 Joint Count evaluates 66 joints for swelling. The temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP), hip, knee, ankle, tarsus, metatarsophalangeal (MTP), and interphalangeal of the feet are included in this joint count.

HAQ-DI - Scales for each question range from 0-3 (0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=Unable to do). The "total" for each category is determined by the highest score (greatest difficulty) for that category. The score for the disability index is the mean of the eight category scores. If more than 2 of the categories or 25% are missing, the scale won't be scored. If fewer than 2 or the categories are missing, the sum of the categories was divided by the number of answered categories.

The score range for the SPA-VAS is 0-100 millimeters. One total score was reported for each assessment, no subscales exist. A lower score on the left side represents a better outcome (less pain) and the higher score is on the right side representing a worse outcome (more pain).

The score range for PGA-VAS is 0-100 millimeters. The patient's assessment of disease activity - with the lowest score on the left side representing "none" to the highest score on the right side representing "extremely active".