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CompletedNCT01526057REFLECTIONSUpdated Nov 19, 2019Results posted

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)

A Phase 2 interventional study of PF-05280586 and MabThera in Rheumatoid Arthritis, sponsored by Pfizer. Completed at 84 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-11-19.

Sponsored by Pfizer · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
220
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

In this study, patients with moderate to severe rheumatoid arthritis who are being treated with methotrexate will receive 2 intravenous treatments with either PF-05280586 or Rituxan (Rituximab) or MabThera (Rituximab). During the course of the study, the effects of the drugs will be assessed by sampling the levels of drug in the blood, blood cell counts, and by comparing these levels among the different treatments. Safety, tolerability and immunologic response also will be evaluated throughout.

02

Conditions studied

  • Rheumatoid Arthritis

Keywords

  • rheumatoid arthritis
  • rituximab
  • methotrexate
  • anti-TNF
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 220 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Confirmed diagnosis of rheumatoid arthritis
  • Meets Class I, II or III of the ACR 1991 Revised Criteria
  • RA seropositivity
  • Stable dose of methotrexate
  • Inadequate response to TNF inhibitors

Exclusion criteria

Exclusion Criteria:

  • Any prior treatment with lymphocyte depleting therapies
  • History of active TB infection
  • Known or screen test positive for specific viruses or indicators of viral infection
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
220 participants (actual)

Study arms

  • Experimental
    A - PF-05280586

    Biological: PF-05280586

  • Active comparator
    B - Rituximab EU

    Biological: MabThera

  • Active comparator
    C- Rituximab-US

    Biological: Rituxan

Interventions

  • BiologicalPF-05280586

    1000 mg, IV on days 1 and 15

  • BiologicalMabThera

    1000 mg, IV on days 1 and 15

  • BiologicalRituxan

    1000 mg, IV on days 1 and 15

06

What researchers measure

Primary outcomes

  1. Maximum Serum Concentration (Cmax) of Rituximab

    Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.

    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

  2. AUC 0-inf of Rituximab

    The AUC 0-inf 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) extrapolated to infinity.

    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

Secondary outcomes

  1. 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

  2. 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

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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

  8. 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)

  9. 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)

  10. 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

  11. 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

  12. 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)

  13. 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

  14. 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.

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

    Time frame: Day 1 up to Day 169

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

07

Results

Posted Nov 19, 2019

Participant flow

This was a multinational, randomized, double-blind, controlled trial in participants with active rheumatoid arthritis (RA) on a background of methotrexate (MTX). The study was conducted at 56 centres in 10 countries. There were a total of 220 participants enrolled in this study.

Participant flow — Overall Study
MilestoneRituximab-PfizerRituximab-European Union (EU)Rituximab-US
Started737473
Completed647167
Not completed936
Withdrew: Withdrawal by subject322
Withdrew: Adverse event311
Withdrew: Death100
Withdrew: Lost to follow-up101
Withdrew: Other101
Withdrew: Protocol violation001

Outcome measures

PrimaryMaximum Serum Concentration (Cmax) of Rituximab

Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.

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
Reported as:
Mean · micrograms per milliliter
Maximum Serum Concentration (Cmax) of Rituximab
micrograms per milliliterRituximab-PfizerRituximab-EURituximab-US
Maximum Serum Concentration (Cmax) of Rituximab453 ± 153422 ± 111430 ± 163
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Test-to-reference ratio: adjusted means: 105.67 · 90% CI 96.91 to 115.21Rituximab-Pfizer is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Test-to-reference ratio: adjusted means: 106.62 · 90% CI 97.65 to 116.41Rituximab-Pfizer is the numerator.
  • Rituximab-EU vs Rituximab-US · Test-to-reference ratio: adjusted means: 100.90 · 90% CI 92.38 to 110.20Rituximab-EU is the numerator.
PrimaryAUC 0-inf of Rituximab

The AUC 0-inf 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) extrapolated to infinity.

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
Reported as:
Mean · ug*hr/mL
AUC 0-inf of Rituximab
ug*hr/mLRituximab-PfizerRituximab-EURituximab-US
AUC 0-inf of Rituximab213000 ± 90400200000 ± 74500214000 ± 95300
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Test-to-reference ratio: adjusted means: 104.19 · 90% CI 92.75 to 117.06
  • Rituximab-Pfizer vs Rituximab-US · Test-to-reference ratio: adjusted means: 100.45 · 90% CI 89.20 to 113.11
  • Rituximab-EU vs Rituximab-US · Test-to-reference ratio: adjusted means: 96.40 · 90% CI 85.57 to 108.60
SecondaryRituximab 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
Reported as:
Mean · ug*hr/mL
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
ug*hr/mLRituximab-PfizerRituximab-EURituximab-US
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)52100 ± 1800049600 ± 1420049200 ± 15900
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Test-to-reference ratio: adjusted means: 103.74 · 90% CI 95.10 to 113.12Rituximab-Pfizer is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Test-to-reference ratio: adjusted means: 105.56 · 90% CI 96.64 to 115.30Rituximab-Pfizer is the numerator.
  • Rituximab-EU vs Rituximab-US · Test-to-reference ratio: adjusted means: 101.76 · 90% CI 93.13 to 111.18Rituximab-EU is the numerator.
SecondaryRituximab 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
Reported as:
Mean · ug*hr/mL
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)
ug*hr/mLRituximab-PfizerRituximab-EURituximab-US
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)198000 ± 79600188000 ± 64300196000 ± 78300
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Test-to-reference ratio: adjusted means: 103.36 · 90% CI 92.81 to 115.12
  • Rituximab-Pfizer vs Rituximab-US · Test-to-reference ratio: adjusted means: 101.33 · 90% CI 90.82 to 113.04
  • Rituximab-EU vs Rituximab-US · Test-to-reference ratio: adjusted means: 98.03 · 90% CI 87.83 to 109.40
SecondaryCD19+ 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)
Reported as:
Mean · cells*day/mL
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
cells*day/mLRituximab-PfizerRituximab-EURituximab-US
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)13312 ± 1330914304 ± 1314612496 ± 13500
SecondaryMinimum 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)
Reported as:
Mean · cells/uL
Minimum Post-Baseline CD19+ B-cell Count (/uL)
cells/uLRituximab-PfizerRituximab-EURituximab-US
Minimum Post-Baseline CD19+ B-cell Count (/uL)0.0 ± 0.280.0 ± 0.000.0 ± 0.18
SecondaryTime 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)
Reported as:
Mean · weeks
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
weeksRituximab-PfizerRituximab-EURituximab-US
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)1.4 ± 1.411.6 ± 1.681.5 ± 1.31
SecondaryDuration 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)
Reported as:
Mean · days
Duration of B-cell Depletion (τB-cell) (Days)
daysRituximab-PfizerRituximab-EURituximab-US
Duration of B-cell Depletion (τB-cell) (Days)126 ± 41.8123 ± 38.6120 ± 40.6
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With CD19+ B-cell Count Recovery
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Percentage of Participants With CD19+ B-cell Count Recovery4.48.79.0
SecondaryArea 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)
Reported as:
Mean · cells*day/uL
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)
cells*day/uLRituximab-PfizerRituximab-EURituximab-US
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)13312.1 ± 13309.1514304.2 ± 13145.7212495.9 ± 13499.97
SecondaryBaseline 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)
Reported as:
Mean · g/L
Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])
g/LRituximab-PfizerRituximab-EURituximab-US
Baseline1.381 ± 0.76171.460 ± 0.80761.394 ± 0.8372
Change from Baseline at Week 10.0 ± 0.150.0 ± 0.17-0.0 ± 0.19
Change from Baseline at Week 20.0 ± 0.170.0 ± 0.170.0 ± 0.20
Change from Baseline at Week 3-0.1 ± 0.18-0.1 ± 0.17-0.0 ± 0.15
Change from Baseline at Week 4-0.1 ± 0.27-0.1 ± 0.20-0.0 ± 0.33
Change from Baseline at Week 5-0.1 ± 0.3-0.1 ± 0.26-0.1 ± 0.23
Change from Baseline at Week 9-0.2 ± 0.32-0.3 ± 0.27-0.2 ± 0.28
Change from Baseline at Week 13-0.2 ± 0.52-0.3 ± 0.30-0.2 ± 0.55
Change from Baseline at Week 17-0.1 ± 0.92-0.3 ± 0.34-0.3 ± 0.34
Change from Baseline at Week 21-0.3 ± 0.42-0.4 ± 0.33-0.3 ± 0.35
Change from Baseline at Week 25-0.4 ± 0.42-0.3 ± 0.30-0.3 ± 0.48
SecondaryPercent (%) 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
Reported as:
Mean · percent change
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
percent changeRituximab-PfizerRituximab-EURituximab-US
Week 13.3 ± 18.621.4 ± 9.57-0.5 ± 9.93
Week 20.1 ± 12.45-0.3 ± 9.420.7 ± 14.06
Week 3-3.4 ± 12.98-4.9 ± 9.95-2.7 ± 9.82
Week 4-5.5 ± 14.77-5.0 ± 10.59-2.2 ± 21.89
Week 5-8.6 ± 16.00-7.9 ± 15.60-5.6 ± 14.39
Week 9-14.4 ± 13.68-16.9 ± 13.69-14.1 ± 13.73
Week 13-11.5 ± 37.17-22.2 ± 13.92-16.2 ± 30.14
Week 175.5 ± 226.39-23.7 ± 16.35-21.6 ± 14.88
Week 21-21.6 ± 17.72-24.7 ± 21.00-21.3 ± 15.69
Week 25-24.2 ± 14.63-21.0 ± 16.95-20.5 ± 21.78
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 334.233.832.9
Week 554.856.842.5
Week 949.360.858.9
Week 1350.770.363.0
Week 1754.867.667.1
Week 2154.262.269.4
Week 2550.060.371.0
SecondaryPercentage 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)
Reported as:
Number · Percentage of participants
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 32.72.72.7
Week 56.86.88.2
Week 912.317.616.4
Week 1319.228.420.5
Week 1715.118.919.2
Week 2113.923.020.8
Week 2516.117.519.4
SecondaryPercentage 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
Reported as:
Number · Percentage of Participants
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit
Percentage of ParticipantsRituximab-PfizerRituximab-EURituximab-US
Week 38.25.49.6
Week 519.216.220.5
Week 921.932.435.6
Week 1335.640.531.5
Week 1724.736.537.0
Week 2127.837.838.9
Week 2521.038.133.9
SecondaryPercentage 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.
Reported as:
Number · Percentage of participants
Percentage of Participants by Anti-drug Antibody (ADA) Status
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Percentage of Participants by Anti-drug Antibody (ADA) Status9.613.512.3
SecondaryPercentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
Time frame:
Day 1 up to Day 169
Reported as:
Number · Percentage of participants
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit0.00.00.0
SecondaryChange 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
Reported as:
Mean · Units on a scale
Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)
Units on a scaleRituximab-PfizerRituximab-EURituximab-US
Baseline5.6862 ± 0.851095.7928 ± 0.95036.2221 ± 0.88162
Change at Week 3-0.9 ± 1.01-0.8 ± 1.13-1.1 ± 1.02
Change at Week 5-1.4 ± 1.17-1.4 ± 1.06-1.6 ± 1.20
Change at Week 9-1.7 ± 1.29-1.8 ± 1.3-2.1 ± 1.37
Change at Week 13-2.0 ± 1.43-2.1 ± 1.33-2.3 ± 1.34
Change at Week 17-2.0 ± 1.32-2.1 ± 1.39-2.4 ± 1.35
Change at Week 21-2.0 ± 1.28-1.9 ± 1.33-2.6 ± 1.35
Change at Week 25-1.7 ± 1.25-2.0 ± 1.30-2.5 ± 1.30
SecondaryPercent 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
Reported as:
Mean · Percent change
Percent Change From Baseline in DAS28-CRP by Visit
Percent changeRituximab-PfizerRituximab-EURituximab-US
Week 3-16.1 ± 19.08-13.6 ± 20.41-18.6 ± 17.63
Week 5-25.4 ± 20.74-24.0 ± 18.22-26.0 ± 21.88
Week 9-31.2 ± 22.31-31.0 ± 21.92-34.2 ± 22.97
Week 13-34.7 ± 24.0-36.9 ± 22.1-37.4 ± 21.42
Week 17-34.9 ± 22.65-35.4 ± 23.28-39.1 ± 21.35
Week 21-35.5 ± 21.99-33.4 ± 22.56-43.2 ± 21.39
Week 25-31.1 ± 22.72-34.6 ± 22.25-40.0 ± 20.55
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 314.510.88.7
Week 522.522.519.4
Week 930.931.525.7
Week 1341.844.432.8
Week 1736.438.032.8
Week 2135.035.447.5
Week 2530.036.241.8
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 333.335.142.0
Week 547.939.443.3
Week 945.643.854.3
Week 1338.837.544.8
Week 1745.539.453.7
Week 2151.746.239.0
Week 2550.046.643.6
SecondaryPercentage 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
Reported as:
Number · Percentage of Participants
Percentage of Participants With No EULAR Response Based on DAS28 by Visit
Percentage of ParticipantsRituximab-PfizerRituximab-EURituximab-US
Week 352.254.149.3
Week 529.638.037.3
Week 923.524.720.0
Week 1319.418.122.4
Week 1718.222.513.4
Week 2113.318.513.6
Week 2520.017.214.5
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 314.510.810.1
Week 523.925.419.4
Week 930.932.925.7
Week 1341.844.432.8
Week 1736.438.032.8
Week 2135.036.947.5
Week 2532.037.941.8
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.75 · 95% CI 0.31 to 1.78Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.06 · 95% CI 0.60 to 1.88Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.06 · 95% CI 0.66 to 1.73Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.06 · 95% CI 0.73 to 1.56Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.05 · 95% CI 0.68 to 1.62Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.05 · 95% CI 0.66 to 1.69Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.19 · 95% CI 0.70 to 2.00Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.70 · 95% CI 0.28 to 1.73Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.81 · 95% CI 0.43 to 1.54Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.83 · 95% CI 0.49 to 1.42Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.79 · 95% CI 0.50 to 1.22Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.90 · 95% CI 0.57 to 1.44Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 1.36 · 95% CI 0.88 to 2.10Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 1.31 · 95% CI 0.78 to 2.18Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.94 · 95% CI 0.36 to 2.45Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.77 · 95% CI 0.41 to 1.44Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.78 · 95% CI 0.47 to 1.31Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.74 · 95% CI 0.48 to 1.13Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.86 · 95% CI 0.55 to 1.36Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 1.29 · 95% CI 0.85 to 1.95Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 1.10 · 95% CI 0.70 to 1.73Rituximab-US is the numerator.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With DAS Remission (DAS <2.6) by Visit
Percentage of participantsRituximab-PfizerRituximab-EURituximab-US
Week 38.74.17.2
Week 516.98.511.9
Week 926.520.520.0
Week 1328.429.225.4
Week 1725.825.423.9
Week 2125.016.930.5
Week 2528.024.123.6
Statistical analysis
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.47 · 95% CI 0.12 to 1.79Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.50 · 95% CI 0.20 to 1.26Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.78 · 95% CI 0.43 to 1.41Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 1.03 · 95% CI 0.61 to 1.74Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.98 · 95% CI 0.56 to 1.74Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.68 · 95% CI 0.34 to 1.36Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-EU · Risk ratio (rr): 0.86 · 95% CI 0.46 to 1.63Rituximab-EU is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.83 · 95% CI 0.27 to 2.60Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.71 · 95% CI 0.31 to 1.62Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.76 · 95% CI 0.41 to 1.40Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.89 · 95% CI 0.51 to 1.57Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.93 · 95% CI 0.51 to 1.68Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 1.22 · 95% CI 0.68 to 2.19Rituximab-US is the numerator.
  • Rituximab-Pfizer vs Rituximab-US · Risk ratio (rr): 0.84 · 95% CI 0.44 to 1.62Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 1.79 · 95% CI 0.44 to 7.20Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 1.41 · 95% CI 0.52 to 3.86Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.97 · 95% CI 0.51 to 1.87Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.87 · 95% CI 0.50 to 1.50Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.94 · 95% CI 0.52 to 1.69Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 1.80 · 95% CI 0.93 to 3.50Rituximab-US is the numerator.
  • Rituximab-EU vs Rituximab-US · Risk ratio (rr): 0.98 · 95% CI 0.51 to 1.89Rituximab-US is the numerator.
SecondaryChange 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
Reported as:
Mean · Units on a scale
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit
Units on a scaleRituximab-PfizerRituximab-EURituximab-US
Baseline1.6541 ± 0.573401.5929 ± 0.535971.7466 ± 0.62081
Change at Week 3-0.2 ± 0.39-0.2 ± 0.34-0.2 ± 0.33
Change at Week 5-0.3 ± 0.39-0.3 ± 0.45-0.3 ± 0.43
Change at Week 9-0.4 ± 0.47-0.5 ± 0.50-0.5 ± 0.54
Change at Week 13-0.4 ± 0.55-0.6 ± 0.56-0.5 ± 0.52
Change at Week 17-0.3 ± 0.49-0.6 ± 0.58-0.5 ± 0.55
Change at Week 21-0.4 ± 0.53-0.6 ± 0.58-0.6 ± 0.61
Change at Week 25-0.4 ± 0.49-0.5 ± 0.63-0.6 ± 0.57
SecondaryPercent 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
Reported as:
Mean · Percentage change
Percent Change From Baseline in HAQ-DI Score by Visit
Percentage changeRituximab-PfizerRituximab-EURituximab-US
Week 3-10.4 ± 37.27-13.2 ± 26.03-9.0 ± 25.68
Week 5-15.1 ± 40.00-23.5 ± 30.45-14.8 ± 43.82
Week 9-22.4 ± 35.96-31.7 ± 34.64-24.5 ± 35.51
Week 13-14.6 ± 50.35-39.5 ± 37.46-30.7 ± 31.91
Week 17-16.9 ± 48.95-39.1 ± 38.85-28.8 ± 36.43
Week 21-21.0 ± 48.04-39.2 ± 38.34-33.5 ± 35.18
Week 25-17.7 ± 54.01-37.1 ± 41.18-38.4 ± 34.60

Adverse events

Collected over Adverse events (AEs) were collected for 28 days after the last administration of study drug or, in the case of incomplete B-cell count recovery, for up to 1 year after Study Day 1.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Rituximab-Pfizer—5/73 (6.8%)49/73 (67.1%)
Rituximab-EU—1/74 (1.4%)40/74 (54.1%)
Rituximab-US—4/73 (5.5%)45/73 (61.6%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventRituximab-PfizerRituximab-EURituximab-US
ArthropathyMusculoskeletal and connective tissue disorders0/730/741/73
Bone neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/730/740/73
Atrial flutterCardiac disorders0/730/741/73
Cardiac failureCardiac disorders1/730/740/73
Cardiac failure congestiveCardiac disorders0/730/741/73
Arthritis bacterialInfections and infestations1/730/740/73
Bacterial sepsisInfections and infestations1/730/740/73
PyelonephritisInfections and infestations0/730/741/73
Septic shockInfections and infestations1/730/740/73
Intentional self-injuryPsychiatric disorders1/730/740/73
Most frequent other events
Showing 10 of 209
Most frequent other events
EventRituximab-PfizerRituximab-EURituximab-US
Upper respiratory tract infectionInfections and infestations7/735/744/73
SinusitisInfections and infestations3/736/742/73
Rheumatoid arthritisMusculoskeletal and connective tissue disorders1/735/745/73
FatigueGeneral disorders5/731/741/73
ArthralgiaMusculoskeletal and connective tissue disorders3/734/744/73
Musculoskeletal painMusculoskeletal and connective tissue disorders4/732/740/73
HypertensionVascular disorders4/732/741/73
NauseaGastrointestinal disorders1/731/744/73
BronchitisInfections and infestations3/732/744/73
HeadacheNervous system disorders3/732/744/73

Baseline characteristics

Modified intent-to-treat (mITT) population included all participants who were randomized and received at least 1 dose of study treatment.

Age, Continuous
Age, Continuous(Years)Rituximab-PfizerRituximab-EURituximab-USTotal
Mean54.9 ± 11.5254.9 ± 11.0753.4 ± 11.8754.4 ± 11.46
Sex: Female, Male
Sex: Female, Male(Participants)Rituximab-PfizerRituximab-EURituximab-USTotal
Female595754170
Male14171950
08

Study locations

84 sites
  • University of Alabama at Bermingham
    Birmingham, Alabama 35249, United States
  • University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076
    Birmingham, Alabama 35294, United States
  • Rheumatology Associates of North Alabama, PC
    Huntsville, Alabama 35801, United States
  • ArthroCare, Arthritis Care & Research, PC
    Gilbert, Arizona 85234, United States
  • Mercy Clinic Hot Springs Communities
    Hot Springs, Arkansas 71913, United States
  • UCLA David Geffen School of Medicine
    Los Angeles, California 90095-1670, United States
  • Ronald Reagan UCLA Medical Center
    Los Angeles, California 90095, United States
  • Desert Medical Advances
    Palm Desert, California 92260, United States
  • Advances In Medicine
    Rancho Mirage, California 92270, United States
  • New England Research Assoc. LLC
    Trumbull, Connecticut 06611, United States
  • Arthritis Associates
    Orlando, Florida 32804, United States
  • University of South Florida - College of Medicine, Frank and Carol Morsani Center
    Tampa, Florida 33612, United States
  • Loyola Center for Health at Burr Ridge
    Burr Ridge, Illinois 60527, United States
  • Loyola Medical Medical Center Outpatient Center
    Maywood, Illinois 60153, United States
  • Loyola University Medical Center Pharmacy
    Maywood, Illinois 60153, United States
  • Illinois Bone and Joint Institute
    Morton Grove, Illinois 60053, United States
  • Loyola Center for health at Oakbrook Terrace North
    Oakbrook Terrace, Illinois 60181, United States
  • Bluegrass Community Research, Inc.
    Lexington, Kentucky 40504, United States
  • Klein & Associates, M.D., P.A.
    Cumberland, Maryland 21502, United States
  • Klein & Associates, M.D., P.A.
    Hagerstown, Maryland 21740, United States
  • Clinical Pharmacology Study Group
    Worcester, Massachusetts 01605, United States
  • UMass Memorial Medical Center - Memorial Campus
    Worcester, Massachusetts 01605, United States
  • UMass Memorial Medical Center-Rheumatology Center-Memorial Campus
    Worcester, Massachusetts 01605, United States
  • Bronson Internal Medicine & Rheumatology
    Battle Creek, Michigan 49015, United States
  • Rheumatology/Arthritis Center
    Lansing, Michigan 48910, United States
  • University Of Nevada School Of Medicine
    Las Vegas, Nevada 89102, United States
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
  • North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology
    Great Neck, New York 11021, United States
  • Box Arthritis & Rheumatology of the Carolinas, PLLC
    Charlotte, North Carolina 28210, United States
  • Hickory Family Practice Associates
    Hickory, North Carolina 28601, United States
  • PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws)
    Hickory, North Carolina 28602, United States
  • PMG Research of Hickory
    Hickory, North Carolina 28602, United States
  • Cincinnati Rheumatic Disease Study Group, Inc.
    Cincinnati, Ohio 45219, United States
  • Health Research of Oklahoma
    Oklahoma City, Oklahoma 73103, United States
  • Altoona Center for Clinical Research
    Duncansville, Pennsylvania 16635, United States
  • The Arthritis Group
    Philadelphia, Pennsylvania 19152, United States
  • Clinical Research Center of Reading, LLP
    Wyomissing, Pennsylvania 19610, United States
  • Arthritis Associates, PLLC
    Hixson, Tennessee 37343, United States
  • Arthritis Clinic
    Jackson, Tennessee 38305, United States
  • West Tennessee Research Institute
    Jackson, Tennessee 38305, United States
  • Metroplex Clinical Research Center
    Dallas, Texas 75231, United States
  • Center For Clinical Trials Of Houston
    Houston, Texas 77004, United States
  • Southwest Rheumatology Research LLC.
    Mesquite, Texas 75150, United States
  • Rheumatology Research Unit
    Maroochydore, Queensland 4558, Australia
  • The Queen Elizabeth Hospital, Department of Rheumatology
    Woodville South, South Australia 5011, Australia
  • St. Vincent's Hospital (Melbourne)
    Fitzroy, Victoria 03065, Australia
  • Centre de Rhumatologie de l'Est du Quebec
    Rimouski, Quebec G5L 8W1, Canada
  • Clinique Medicale du Phare
    Rimouski, Quebec G5L IJ5, Canada
  • Centre de Recherche Musculo-Squelettique
    Trois-Rivieres, Quebec G8Z 1Y2, Canada
  • Pharmacie Matte et Petit
    Quebec, G1V 3M7, Canada
  • Centre de Rhumatologie St-Louis
    Quebec, G1W 4R4, Canada
  • Clinica Medellin S.A Sede Centro
    Medellin, Antioquia, Colombia
  • Mix Supplier S.A
    Medellin, Antioquia, Colombia
  • Rodrigo Botero S.A.S.
    Medellin, Antioquia, Colombia
  • Cediul S.A.
    Barranquilla, Atlantico, Colombia
  • Clinica Bonnadona - Prevenir S.A.
    Barranquilla, Atlantico, Colombia
  • Clinica de la Costa Ltdz.
    Barranquilla, Atlantico, Colombia
  • IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S.
    Barranquilla, Atlantico, Colombia
  • Sabbag Radiologos Ltda.
    Barranquilla, Atlantico, Colombia
  • Cerid S.A.
    Barranquilla, Colombia, Atlántico, Colombia
  • Congregacion de las Hemanas Franciscanas Misioneras de Maria Auxiliadora - Clinica La Asuncion
    Barranquilla, Colombia, Atlántico, Colombia
  • IPS Clinica General del Norte S.A.
    Barranquilla, Colombia, Atlántico, Colombia
  • Centro de Reumatologia y Ortopedia
    Barranquilla, Atlántico, Colombia
  • Schlosspark-Klinik GMBH, Internal Medicine II
    Berlin, 14059, Germany
  • The Chaim Sheba Medical Center Department of Internal Medicine B
    Ramat Gan, 52621, Israel
  • Cliditer, S.A. de C.V.
    Mexico, D.f. 06700, Mexico
  • Private Office
    Guadalajara, Jalisco 06726, Mexico
  • Centro De Investigacion Y Atencion Integral Durango CIAID
    Durango, 34270, Mexico
  • Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
    San Luis Potosi, 78200, Mexico
  • LLC CDCR "Healthy Joints"
    Novosibirsk, Novosibirsk Region 630091, Russian Federation
  • GBUZ City Clinical Hospital #7
    Kazan, Tatarstan 420103, Russian Federation
  • State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
    Kemerovo, 650000, Russian Federation
  • State Budgetary Institution of Healthcare of Nizhegorodskiy Region
    Nizhny Novgorod, 603005, Russian Federation
  • St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25
    Saint-Petersburg, 190068, Russian Federation
  • State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin
    Samara, 443095, Russian Federation
  • Llc Ava-Peter
    St. Petersburg, 191014, Russian Federation
  • Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital"
    Tomsk, 634063, Russian Federation
  • Panorama Medical Centre
    Panorama, Cape Town 7500, South Africa
  • Dr. Jan Fourie Medical Centre
    Dundee, Kwa-zulu Natal 3000, South Africa
  • Bexley Wing - St. James's University Hospital
    Leeds, UK LS9 7TF, United Kingdom
  • Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
    Leeds, LS1 3EX, United Kingdom
  • "The University of Leeds,
    Leeds, LS7 4SA, United Kingdom
  • Pharmacy Dispensing - Bexley Wing - St. James's University Hospital
    Leeds, LS9 7TF, United Kingdom
  • Whipps Cross University Hospital
    London, E11 1NR, United Kingdom
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References and documents

Publications

  • Williams JH, Hutmacher MM, Zierhut ML, Becker JC, Gumbiner B, Spencer-Green G, Melia LA, Liao KH, Suster M, Yin D, Li R, Meng X. Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab. Br J Clin Pharmacol. 2016 Dec;82(6):1568-1579. doi: 10.1111/bcp.13094. Epub 2016 Sep 22. PubMed 27530379 ↗

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01526057
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Feb 3, 2012
Start date
Mar 20, 2012
Primary completion
Aug 13, 2013
Completion
May 7, 2014
Results posted
Nov 19, 2019
Last update
Nov 19, 2019

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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