Trial Outcomes & Findings for A Study Comparing Infusion Rates of Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis (NCT NCT00887341)

Last Updated: 2014-10-22

Results Overview

An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24

Results posted on

2014-10-22

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab, 1 Hour Infusions Participants received tocilizumab 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Overall Study STARTED	37	39
Overall Study COMPLETED	35	36
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab, 1 Hour Infusions Participants received tocilizumab 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Overall Study Refused treatment	1	0
Overall Study Withdrawal by Subject	1	1
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Study Comparing Infusion Rates of Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.	Total n=76 Participants Total of all reporting groups
Age, Continuous	52.65 years STANDARD_DEVIATION 12.71 • n=5 Participants	52.46 years STANDARD_DEVIATION 10.47 • n=7 Participants	52.55 years STANDARD_DEVIATION 11.54 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	28 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening, Baseline, and Weeks 4, 8, 12, 16, 20, and 24

Population: ITT Population

An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants With an Infusion Reaction Within 24 Hours After Infusion	29.7 percentage of participants	17.9 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Discontinuing Tocilizumab in Response to an AE or Serious AE (SAE)	2.7 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Discontinuing Tocilizumab for Any Reason	2.7 percentage of participants	2.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease (participant-rated arthritis 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; DAS28 less than (\<) 2.6 = remission. A reduction of at least 1.2 units was considered a clinically significant difference.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Week 4	56.7 percentage of participants	61.9 percentage of participants
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Week 8	58.6 percentage of participants	74.1 percentage of participants
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Week 12	77.8 percentage of participants	92.3 percentage of participants
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Week 16	88.5 percentage of participants	88.0 percentage of participants
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Week 20	88.9 percentage of participants	84.0 percentage of participants
Percentage of Participants With a Reduction of at Least 1.2 Units on the Disease Activity Scale Based on 28-Joint Count (DAS28) by Visit Final visit	80.8 percentage of participants	91.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr), and Patient's Global Assessment of Disease (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; DAS28 \<2.6=remission.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Week 4	22.2 percentage of participants	32.0 percentage of participants
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Week 8	25.0 percentage of participants	60.0 percentage of participants
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Week 12	46.9 percentage of participants	77.1 percentage of participants
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Week 16	59.4 percentage of participants	77.1 percentage of participants
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Week 20	68.8 percentage of participants	79.4 percentage of participants
Percentage of Participants Achieving a DAS28 Score <3.2 by Visit Final visit	64.3 percentage of participants	80.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT population

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and Patient's Global Assessment of Disease (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; DAS28 \<2.6=remission.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Week 4	11.1 percentage of participants	20.0 percentage of participants
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Week 8	18.8 percentage of participants	34.3 percentage of participants
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Week 12	34.4 percentage of participants	57.1 percentage of participants
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Week 16	40.6 percentage of participants	51.4 percentage of participants
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Week 20	56.3 percentage of participants	58.8 percentage of participants
Percentage of Participants Achieving a DAS28 Score <2.6 (Remission) Final visit	46.4 percentage of participants	74.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, and Final Visit

Population: ITT Population; n (number)=number of participants analyzed for the specified parameter at a given visit.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=38 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
DAS28 Score by Visit Baseline visit (n=36,38)	5.75 units on a scale Standard Deviation 1.18	5.32 units on a scale Standard Deviation 1.14
DAS28 Score by Visit Week 4 (n=36,25)	4.28 units on a scale Standard Deviation 1.33	3.62 units on a scale Standard Deviation 1.27
DAS28 Score by Visit Week 8 (n=32,35)	4.14 units on a scale Standard Deviation 1.54	3.05 units on a scale Standard Deviation 1.20
DAS28 Score by Visit Week 12 (n=32,35)	3.30 units on a scale Standard Deviation 1.32	2.66 units on a scale Standard Deviation 1.04
DAS28 Score by Visit Week 16 (n=32,35)	3.07 units on a scale Standard Deviation 1.50	2.64 units on a scale Standard Deviation 1.18
DAS28 Score by Visit Week 20 (n=32,34)	2.78 units on a scale Standard Deviation 1.33	2.41 units on a scale Standard Deviation 1.22
DAS28 Score by Visit Final visit (n=28,31)	2.72 units on a scale Standard Deviation 1.40	2.19 units on a scale Standard Deviation 1.06
DAS28 Score by Visit LOCF visit (n=37,38)	2.92 units on a scale Standard Deviation 1.56	2.37 units on a scale Standard Deviation 1.13

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

ACR20 response defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and acute phase reactive factors (ESR or C-Reactive Protein \[CRP\])

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Week 4	26.5 percentage of participants	48.5 percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Week 8	51.5 percentage of participants	59.4 percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Week 12	60.0 percentage of participants	69.7 percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Week 16	74.2 percentage of participants	60.6 percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Week 20	81.8 percentage of participants	54.5 percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) Final visit	70.6 percentage of participants	64.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

ACR50 response defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Week 4	11.4 percentage of participants	20.6 percentage of participants
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Week 8	26.5 percentage of participants	39.4 percentage of participants
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Week 12	35.5 percentage of participants	47.1 percentage of participants
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Week 16	53.1 percentage of participants	45.5 percentage of participants
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Week 20	65.6 percentage of participants	45.5 percentage of participants
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) Final visit	54.5 percentage of participants	45.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

ACR70 response defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Week 4	0.0 percentage of participants	2.9 percentage of participants
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Week 8	12.1 percentage of participants	14.7 percentage of participants
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Week 12	22.6 percentage of participants	28.6 percentage of participants
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Week 16	25.1 percentage of participants	28.6 percentage of participants
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Week 20	33.3 percentage of participants	29.4 percentage of participants
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) Final visit	38.2 percentage of participants	30.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

ACR90 response defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Week 4	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Week 8	2.9 percentage of participants	2.9 percentage of participants
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Week 12	3.1 percentage of participants	5.7 percentage of participants
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Week 16	3.0 percentage of participants	11.1 percentage of participants
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Week 20	8.8 percentage of participants	5.7 percentage of participants
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) Final visit	12.1 percentage of participants	11.1 percentage of participants

SECONDARY outcome

Timeframe: Screening, Baseline, Weeks 4, 8, 12, 16, 20, and Final Visit

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as Rheumatoid Arthritis. CRP is measured in milligrams per liter (mg/L).

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=38 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
C-Reactive Protein (CRP) Levels Screening (n=35,38)	9.28 mg/L Standard Deviation 9.64	10.76 mg/L Standard Deviation 11.88
C-Reactive Protein (CRP) Levels Baseline (n=30,35)	11.49 mg/L Standard Deviation 15.39	13.68 mg/L Standard Deviation 26.21
C-Reactive Protein (CRP) Levels Week 4 (n=37,37)	6.45 mg/L Standard Deviation 13.52	4.29 mg/L Standard Deviation 8.16
C-Reactive Protein (CRP) Levels Week 8 (n=34,37)	4.84 mg/L Standard Deviation 10.98	1.93 mg/L Standard Deviation 2.84
C-Reactive Protein (CRP) Levels Week 12 (n=33,36)	2.94 mg/L Standard Deviation 5.80	1.78 mg/L Standard Deviation 3.95
C-Reactive Protein (CRP) Levels Week 16 (n=35,38)	2.81 mg/L Standard Deviation 6.86	2.08 mg/L Standard Deviation 4.00
C-Reactive Protein (CRP) Levels Week 20 (n=34,36)	1.97 mg/L Standard Deviation 2.52	2.66 mg/L Standard Deviation 7.89
C-Reactive Protein (CRP) Levels Final visit (n=31,34)	5.42 mg/L Standard Deviation 13.27	2.26 mg/L Standard Deviation 4.57

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12,16, 20, and 24

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

ESR is an acute phase reactant measured in mm/hr. Reduction in ESR indicates improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Erythrocyte Sedimentation Rate Screening (n=37,37)	37.70 mm/hr Standard Deviation 25.19	31.19 mm/hr Standard Deviation 18.62
Erythrocyte Sedimentation Rate Baseline (n=30,30)	42.53 mm/hr Standard Deviation 28.60	30.40 mm/hr Standard Deviation 17.78
Erythrocyte Sedimentation Rate Week 4 (n=36,29)	15.03 mm/hr Standard Deviation 16.16	11.41 mm/hr Standard Deviation 8.93
Erythrocyte Sedimentation Rate Week 8 (n=33,36)	15.36 mm/hr Standard Deviation 17.06	8.67 mm/hr Standard Deviation 8.82
Erythrocyte Sedimentation Rate Week 12 (n=32,35)	12.19 mm/hr Standard Deviation 16.63	6.77 mm/hr Standard Deviation 6.47
Erythrocyte Sedimentation Rate Week 16 (n=33,36)	11.97 mm/hr Standard Deviation 15.39	6.50 mm/hr Standard Deviation 6.22
Erythrocyte Sedimentation Rate Week 20 (n=33,34)	13.83 mm/hr Standard Deviation 19.91	6.29 mm/hr Standard Deviation 6.76
Erythrocyte Sedimentation Rate Final visit (n=30,33)	12.00 mm/hr Standard Deviation 13.77	6.70 mm/hr Standard Deviation 5.59

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24

Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.

HAQ-DI is a self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI scores range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=38 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
HAQ-DI Score by Visit Baseline (n=37,37)	1.6 units on a scale Standard Deviation 0.7	1.4 units on a scale Standard Deviation 0.7
HAQ-DI Score by Visit Week 4 (n=37,37)	1.4 units on a scale Standard Deviation 0.7	1.0 units on a scale Standard Deviation 0.6
HAQ-DI Score by Visit Week 8 (n=35,37)	1.3 units on a scale Standard Deviation 0.8	0.9 units on a scale Standard Deviation 0.7
HAQ-DI Score by Visit Week 12 (n=31,36)	1.1 units on a scale Standard Deviation 0.7	0.8 units on a scale Standard Deviation 0.6
HAQ-DI Score by Visit Week 16 (n=33,38)	1.0 units on a scale Standard Deviation 0.8	0.8 units on a scale Standard Deviation 0.6
HAQ-DI Score by Visit Week 20 (n=35,37)	1.0 units on a scale Standard Deviation 0.7	0.8 units on a scale Standard Deviation 0.7
HAQ-DI Score by Visit Final visit (n=35,35)	0.9 units on a scale Standard Deviation 0.8	0.8 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20 and Final Visit

Population: ITT Population

Outcome measures

Outcome measures
Measure	Tocilizumab, 1 Hour Infusions n=37 Participants Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 Participants Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Week 4	48.6 percentage of participants	48.6 percentage of participants
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Week 8	62.9 percentage of participants	54.3 percentage of participants
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Week 12	64.5 percentage of participants	58.8 percentage of participants
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Week 16	72.7 percentage of participants	52.8 percentage of participants
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Week 20	68.6 percentage of participants	54.3 percentage of participants
Percentage of Participants With Improvement of at Least 0.22 in HAQ-DI Final visit	68.6 percentage of participants	61.8 percentage of participants

Adverse Events

Tocilizumab, 1 Hour Infusions

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Tocilizumab, 31 Minute Infusions

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab, 1 Hour Infusions n=37 participants at risk Participants received tocilizumab 8 mg/kg via IV infusion (over 1 hour), once every 4 weeks for 6 infusions (up to 24 weeks).	Tocilizumab, 31 Minute Infusions n=39 participants at risk Participants received tocilizumab 8 mg/kg via IV infusion, once every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour; the remaining 5 infusions were administered over a period of 31 minutes as long as no infusion reactions occurred. If an infusion reaction occurred, 1 hour infusions were used for all subsequent remaining infusions.
Gastrointestinal disorders Abdominal pain	2.7% 1/37 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)	0.00% 0/39 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)
Gastrointestinal disorders Crohn's Disease	2.7% 1/37 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)	0.00% 0/39 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)
Infections and infestations Hepatitis	0.00% 0/37 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)	2.6% 1/39 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)
Infections and infestations Infection	0.00% 0/37 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)	2.6% 1/39 • Adverse events were recorded from the date of Screening until the End of Study (24 Weeks)

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER