A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor

The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-ated rheumatoid arthritis \[RA\] activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Time frame: Week 24

Population: Intent to Treat (ITT) population: all participants who signed informed consent, received at least 1 dose of study drug, and where DAS28 was measured at least once under study medication (Weeks 8, 16, or 24 or unscheduled or withdrawal visit up to Week 24); those with no RA or no DAS28 score at screening were excluded, regardless if treated or not.

Mean CRP as measured as an acute phase reactant by mg per deciliter (mg/dL) at screening, Days 1 and 15, and Weeks 8, 16, and 24.

Time frame: Screening, Days 1 and 15, and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant-rated RA assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n (number) = number of participants assessed at a given visit.

Mean ESR, as an acute phase reactant, measured in mm/hr at screening, Days 1 and 15, and Weeks 8, 16, and 24.

Time frame: Screening, Days 1 and 15, and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The FACIT fatigue scale is base on a 13-item questionnaire to assess the therapy-induced fatigue. Participants were requested to score each question on a scale ranging from 0 (best) to 4 (worst). The scoring system of the FACIT fatigue scale adds up to a total scale ranging from 0 (best) to 52 (worst). The assessment was originally developed for chronic illnesses and is now validated for patients with rheumatoid arthritis (RA). The questionnaire was provided in a German translation.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific sub-category items. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

Participants were to assess the disease (RA) activity on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as no disease activity (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as maximum disease activity (maximum arthritis disease activity).

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

Participants were to assess their current level of pain on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as no pain and the right-hand (100 mm) as unbearable pain.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in tender or swollen joint counts and ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Patient's Global Assessment of Disease Activity, 3) Patient's Assessment of Pain, 4) participant assessment of functional disability via a HAQ-DI, and 5) C-reactive protein or ESR at each visit.

Time frame: Weeks 8, 16, and 24

Population: ITT population

Percentage of participants achieving a response by EULAR category, including 'moderate', 'good', or no response at follow-up Weeks 8, 16, and 24. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline \>1.2 with a DAS28 score ≤ 3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders had a change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with a DAS28 score of \>5.1.

Time frame: Weeks 8, 16, and 24

Population: ITT population

Percentage of participants with remission defined as DAS28 \<2.6 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.

Time frame: Week 24

Population: ITT population

The DAS28-based EULAR response criteria were used to measure individual responses as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders experienced a change from baseline of \>1.2 with a DAS28 score ≤3.2 and moderate responders experienced a change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1.

Time frame: Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit

Percentage of participants with low disease activity defined as DAS28 ≤3.2 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity).

Time frame: Week 24

Population: ITT population

Physicians assessed the disease (RA) activity on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as no disease activity (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as maximum disease activity (maximum arthritis disease activity).

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

Mean RF as measured by international unit per milliliter (IU/mL) at screening and Weeks 8, 16, and 24.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to two distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The 28 joints to be assessed for tenderness and swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.

The 28 joints to be assessed for tenderness and swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.

Time frame: Screening and Weeks 8, 16, and 24

Population: ITT population; n=number of participants assessed at a given visit.