Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis

A participant was a responder if the following 3 criteria for improvement from Baseline were met:

• ≥ 20% improvement in tender joint count;
• ≥ 20% improvement in swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein level.

The DAS28-CRP 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;
• C-reactive protein (CRP) level
• Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable).

The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity.

A repeated measures analysis with the DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and the baseline DAS28-CRP measurement as predictors in the model was performed.

A participant was a responder if the following 3 criteria for improvement from Baseline were met:

• ≥ 20% improvement in tender joint count;
• ≥ 20% improvement in swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein level.

A participant was a responder if the following 3 criteria for improvement from Baseline were met:

• ≥ 50% improvement in tender joint count;
• ≥ 50% improvement in swollen joint count; and
• ≥ 50% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein level.

A participant was a responder if the following 3 criteria for improvement from Baseline were met:

• ≥ 70% improvement in tender joint count;
• ≥ 70% improvement in swollen joint count; and
• ≥ 70% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-Reactive Protein level.

Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale:

1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question "is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product" was yes.

A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria:

• fatal
• life threatening (places the subject at immediate risk of death)
• requires inpatient hospitalization or prolongation of existing hospitalization
• results in persistent or significant disability/incapacity
• congenital anomaly/birth defect
• other medically important serious event.

Two validated assays were used to detect the presence of anti-drug antibodies. Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against ABP 501 and adalimumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501 or adalimumab (Neutralizing Antibody Assay).

Developing antibody incidence is defined as a negative or no antibody result at baseline and a positive antibody result at a post-baseline time point.