A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01)

Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)

The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration.

Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion

Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)

The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T.

Time frame: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion

CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)

The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)

Minimum Post-Baseline CD19+ B-cell Count (/uL)

The lowest CD19+ B-cell count measured in a participant's blood post-baseline.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)

Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)

The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)

Duration of B-cell Depletion (τB-cell) (Days)

The τB-cell is defined as the time interval over which the B-cell count was \<0.3 cells/uL or the detection limit.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)

Percentage of Participants With CD19+ B-cell Count Recovery

The percentage of participants with CD19+ B-cell counts which fell to \<50% of Baseline value during treatment and which recovered to ≥50% of Baseline value at End of Treatment.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25

Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)

The AUC 0-T, B-cell refers to the CD19+ B-cell count over time. It represents the total B-cells over time, from time 0 (the point of drug administration) to the last measured count at time T.

Time frame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)

Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])

The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit.

Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT)

Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)

The percentage change from Baseline in circulating IgM by visit.

Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25

Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit

ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit

ACR70 response: ≥70% improvement in tender joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participantss who rolled over to the extension study were not included in the non-responder imputation from that point on.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)

Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit

ACR50 response: ≥50% improvement in tender joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants by Anti-drug Antibody (ADA) Status

Presence of anti-rituximab antibodies in blood. Participants with a positive antibody status at any time during the study were defined as having overall positive antibody status; participants with a negative antibody status throughout the study were defined as having overall negative antibody status.

Time frame: Days 1 up to Day 169.

Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit

Time frame: Day 1 up to Day 169

Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)

DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.

Time frame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25

Percent Change From Baseline in DAS28-CRP by Visit

DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, DAS28-CRP greater than (\>)3.2 to ≤5.1 implied moderate to high disease activity, and DAS28-CRP less than (\<)2.6 implied remission.

Time frame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit

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: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit

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: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With No EULAR Response Based on DAS28 by Visit

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: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6, or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit

DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. p-value of 9999 indicates p-value is not applicable.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Percentage of Participants With DAS Remission (DAS <2.6) by Visit

DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission. p-value of 9999 indicates p-value is not applicable.

Time frame: Weeks 3, 5, 9, 13, 17, 21 and 25

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25

Percent Change From Baseline in HAQ-DI Score by Visit

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25