A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone

The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

• ≥ 20% improvement in 68-tender joint count;
• ≥ 20% improvement in 66-swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity;
• Patient global assessment of disease activity;
• Patient assessment of pain;
• Health Assessment Questionnaire - Disability Index (HAQ-DI);
• High-sensitivity C-reactive protein (hsCRP).

The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12.

The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

A DAS28 score less than or equal to 3.2 indicates low disease activity.

The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.

A negative change from Baseline in the overall score indicates improvement.

The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

The physical component summary score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.

Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.

DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.

CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.

The FACIT-Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a five point Likert scale from 0 (not at all) to 4 (very much). The FACIT-Fatigue scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:

• ≥ 50% improvement in 68-tender joint count;
• ≥ 50% improvement in 66-swollen joint count; and
• ≥ 50% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity;
• Patient global assessment of disease activity;
• Patient assessment of pain;
• Health Assessment Questionnaire - Disability Index (HAQ-DI);
• High-sensitivity C-reactive protein (hsCRP).

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:

• ≥ 70% improvement in 68-tender joint count;
• ≥ 70% improvement in 66-swollen joint count; and
• ≥ 70% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity;
• Patient global assessment of disease activity;
• Patient assessment of pain;
• Health Assessment Questionnaire - Disability Index (HAQ-DI);
• High-sensitivity C-reactive protein (hsCRP).

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

• ≥ 20% improvement in 68-tender joint count;
• ≥ 20% improvement in 66-swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity;
• Patient global assessment of disease activity;
• Patient assessment of pain;
• Health Assessment Questionnaire - Disability Index (HAQ-DI);
• High-sensitivity C-reactive protein (hsCRP).