Trial Outcomes & Findings for Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants (NCT NCT02573012)

NCT ID: NCT02573012

Last Updated: 2019-11-01

Results Overview

The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 314 participants
• Primary outcome timeframe: Baseline to Week 24
• Results posted on: 2019-11-01

Participant Flow

314 participants were enrolled in the study; 55 participants discontinued the study prior to randomization; 259 participants were randomized.

Participant milestones

Measure	Tocilizumab+Prednisone (Tapering Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Overall Study STARTED	131	128
Overall Study COMPLETED	116	113
Overall Study NOT COMPLETED	15	15

Reasons for withdrawal

Measure	Tocilizumab+Prednisone (Tapering Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Overall Study Adverse Event	5	5
Overall Study Lack of Efficacy	5	4
Overall Study Non-compliance	1	2
Overall Study Withdrawal by Subject	2	2
Overall Study Study Ended per Protocol	1	0
Overall Study Physician Decision	1	2

Baseline Characteristics

Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants

Baseline characteristics by cohort

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.	Total n=259 Participants Total of all reporting groups
Age, Continuous	54.8 Years STANDARD_DEVIATION 14.0 • n=5 Participants	54.0 Years STANDARD_DEVIATION 12.8 • n=7 Participants	54.4 Years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	97 Participants n=7 Participants	200 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	31 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	120 Participants n=5 Participants	114 Participants n=7 Participants	234 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	129 Participants n=5 Participants	123 Participants n=7 Participants	252 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization	0.538 Score on a scale Interval 0.346 to 0.729	-0.075 Score on a scale Interval -0.271 to 0.121

SECONDARY outcome

Timeframe: Week 24

Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 > 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Treatment Success	64.9 Percentage of Participants Interval 56.1 to 73.0	77.3 Percentage of Participants Interval 69.1 to 84.3

SECONDARY outcome

Timeframe: Baseline and Week 24

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index is calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter (cm) visual analog scale (VAS) + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 100 mm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	2.663 Score on a scale Interval 1.454 to 3.872	0.321 Score on a scale Interval -0.914 to 1.556

SECONDARY outcome

Timeframe: 24 weeks

Percentage of participants with >=1 flare

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Percentage of Participants With >=1 Flare	26.0 Percentage of Participants	10.9 Percentage of Participants

SECONDARY outcome

Timeframe: Randomization to 24 weeks

The mean time of onset for the first RA flare since randomization.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Time to First RA Flare	15.64 Weeks Standard Deviation 7.13	12.11 Weeks Standard Deviation 7.96

SECONDARY outcome

Timeframe: Randomization to 24 weeks

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Percentage of Visits With RA Flares 2 Visits	6.9 Percentage of visits with flares	3.9 Percentage of visits with flares
Percentage of Visits With RA Flares 3 Visits	2.3 Percentage of visits with flares	0 Percentage of visits with flares
Percentage of Visits With RA Flares >3 Visits	0.8 Percentage of visits with flares	0 Percentage of visits with flares
Percentage of Visits With RA Flares 1 Visit	16.0 Percentage of visits with flares	7.0 Percentage of visits with flares

SECONDARY outcome

Timeframe: Randomization to 24 weeks

The proportion of participants with at least one administration of RA flare rescue medication.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Percentage of Participants With >=1 Administration of Flare Rescue Medication	20.6 Percentage of Participants	6.3 Percentage of Participants

SECONDARY outcome

Timeframe: Randomization to 24 weeks

Time of onset of first administration of RA flare rescue medication since randomization date

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Time to First Administration of Flare Rescue Medication	13.59 Weeks Standard Deviation 6.77	8.76 Weeks Standard Deviation 5.26

SECONDARY outcome

Timeframe: Randomization to 24 weeks

Proportion of participants who received courses of RA flare rescue medication by number of courses received.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Number of Administrations of Flare Rescue Medication 0 courses	79.4 Percentage of Participants	93.8 Percentage of Participants
Number of Administrations of Flare Rescue Medication 1 course	15.3 Percentage of Participants	3.9 Percentage of Participants
Number of Administrations of Flare Rescue Medication 2 courses	4.6 Percentage of Participants	1.6 Percentage of Participants
Number of Administrations of Flare Rescue Medication 3 courses	0 Percentage of Participants	0.8 Percentage of Participants
Number of Administrations of Flare Rescue Medication >3 courses	0.8 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Randomization to 24 weeks

Population: Safety Population. The cumulative flare rescue prednisone dose population is based upon the number of participants who required rescue treatment.

In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 * 1 mg) + (3/4 * number of capsules taken during week 5 to 8 * 1 mg) + (1/2 * number of capsules taken during week 9 to 12 * 1 mg) + (1/4 * number of capsules taken during week 13 to 16 * 1 mg). In continued arm, cumulative dose = (1/4 * number of capsule taken * 5 mg).

Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Cumulative Prednisone Exposure (Dose) Cumulative blinded prednisone dose	267.099 mg Standard Deviation 40.048	769.459 mg Standard Deviation 175.882
Cumulative Prednisone Exposure (Dose) Cumulative flare rescue prednisone dose	98.519 mg Standard Deviation 51.921	121.875 mg Standard Deviation 54.898
Cumulative Prednisone Exposure (Dose) Cumulative prednisone dose	287.405 mg Standard Deviation 63.184	777.136 mg Standard Deviation 172.881

SECONDARY outcome

Timeframe: Randomization to Week 24

Population: Intent to Treat population. The number of participants for LDA at Week 24 and Remission at Week 24 are based upon the number with LDA at baseline and DAS28-ESR ≤ 2.6 at baseline respectively.

The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24.

LDA was defined as DAS28 ESR score <= 3.2. Remission was defined as DAS28 ESR score <= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 <= DAS28-ESR at baseline.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level LDA at baseline	97.7 Percentage of Participants	96.9 Percentage of Participants
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level LDA at Week 24	73.4 Percentage of Participants	83.1 Percentage of Participants
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level Baseline DAS28-ESR ≤ 2.6	78.6 Percentage of Participants	76.6 Percentage of Participants
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level Remission at Week 24	61.2 Percentage of Participants	81.6 Percentage of Participants
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level Maintained baseline activity at Week 24	36.6 Percentage of Participants	54.7 Percentage of Participants

SECONDARY outcome

Timeframe: 24 weeks

Percentage of participants who permanently discontinue study treatment due to insufficient flare control

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control	0 Percentage of Participants	0.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Count of swollen joints based upon 66 assessed joints.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts	0.129 Swollen joints Standard Deviation 6.687	-0.107 Swollen joints Standard Deviation 1.618

SECONDARY outcome

Timeframe: Baseline to Week 24

Count of tender joints based on 68 assessed joints.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts	0.793 Tender joints Standard Deviation 7.764	-0.330 Tender joints Standard Deviation 2.729

SECONDARY outcome

Timeframe: Baseline to Week 24

The ACR patient's assessment of pain is scored on a visual analog scale (VAS) from 0 (no pain) to 100 mm (unbearable pain). A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain	4.648 mm Standard Deviation 24.315	-8.010 mm Standard Deviation 25.980

SECONDARY outcome

Timeframe: Baseline to Week 24

The ACR patient's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity	0.280 cm Standard Deviation 2.000	-0.153 cm Standard Deviation 1.506

SECONDARY outcome

Timeframe: Baseline to Week 24

The ACR physician's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity	0.345 cm Standard Deviation 1.463	-0.248 cm Standard Deviation 1.167

SECONDARY outcome

Timeframe: Baseline to Week 24

A measure of self-perceived disability containing 20 questions in eight categories and including additional section about aid from other people and devices needed to correct the disabilities. Scores range from 0 to 3, with higher scores indicating worse disability.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI)	0.167 Score on a scale Standard Deviation 0.486	-0.087 Score on a scale Standard Deviation 0.527

SECONDARY outcome

Timeframe: Baseline to Week 24

Change from baseline in the acute phase reactant hsCRP

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP)	-0.135 mg/dL Standard Deviation 1.470	-0.040 mg/dL Standard Deviation 0.277

SECONDARY outcome

Timeframe: Baseline to Week 24

Change from baseline in the acute phase reactant ESR

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR)	1.517 mm/hr Standard Deviation 7.892	-0.679 mm/hr Standard Deviation 5.433

SECONDARY outcome

Timeframe: Baseline and Week 24

The RAID is a participant-completed questionnaire specific for RA consisting of a 0-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result. A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score	0.469 Score on a scale Standard Deviation 2.109	-0.220 Score on a scale Standard Deviation 1.940

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent to Treat population.

The WPAI:SHP is a 6-item questionnaire to measure performance impairment of work and regular daily activity and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score range from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity. A positive change in score indicates impairment, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score Percent work time missed due to problem	4.535 Score on a scale Standard Deviation 23.283	0.572 Score on a scale Standard Deviation 31.455
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score Percent impairment while working due to problem	-0.851 Score on a scale Standard Deviation 24.920	-5.584 Score on a scale Standard Deviation 23.343
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score Percent overall work impairment due to problem	6.219 Score on a scale Standard Deviation 29.223	-6.191 Score on a scale Standard Deviation 30.531
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score Percent activity impairment due to problem	3.398 Score on a scale Standard Deviation 23.786	-4.190 Score on a scale Standard Deviation 21.608

SECONDARY outcome

Timeframe: Randomization to Week 24

The SDAI is the numerical sum of 5 outcome parameters: tender and swollen joint count based on a 28-joint assessment, patient and physician global assessment of disease activity according to 100-mm visual analog scale (VAS) and level of C-reactive protein in milligrams per deciliter (mg/dL, normal <1 mg/dl). The total SDAI score range is 0-86, where higher scores indicate increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.

Outcome measures

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 Participants Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24	2.511 Score on a scale Interval 1.296 to 3.727	0.248 Score on a scale Interval -0.994 to 1.489

Adverse Events

Tocilizumab+Prednisone (Tapering Dose)

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

Tocilizumab+Prednisone (Constant Dose)

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 participants at risk Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 participants at risk Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Musculoskeletal and connective tissue disorders SPINAL COLUMN STENOSIS	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Blood and lymphatic system disorders NEUTROPENIA	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Cardiac disorders ATRIAL FIBRILLATION	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Infections and infestations PNEUMONIA	0.76% 1/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28
Infections and infestations CELLULITIS GANGRENOUS	0.00% 0/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28
Investigations BLOOD GLUCOSE FLUCTUATION	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.76% 1/131 • Randomization to Week 28	0.00% 0/128 • Randomization to Week 28
Nervous system disorders SCIATICA	0.00% 0/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28
Immune system disorders DRUG HYPERSENSITIVITY	0.00% 0/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28
Psychiatric disorders PSYCHOTIC DISORDER	0.00% 0/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28
Respiratory, thoracic and mediastinal disorders ASTHMA	0.00% 0/131 • Randomization to Week 28	0.78% 1/128 • Randomization to Week 28

Other adverse events

Measure	Tocilizumab+Prednisone (Tapering Dose) n=131 participants at risk Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.	Tocilizumab+Prednisone (Constant Dose) n=128 participants at risk Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
Infections and infestations NASOPHARYNGITIS	9.9% 13/131 • Randomization to Week 28	7.0% 9/128 • Randomization to Week 28
Gastrointestinal disorders DIARRHOEA	5.3% 7/131 • Randomization to Week 28	3.9% 5/128 • Randomization to Week 28
Investigations ALANINE AMINOTRANSFERASE INCREASED	6.9% 9/131 • Randomization to Week 28	2.3% 3/128 • Randomization to Week 28
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	6.9% 9/131 • Randomization to Week 28	1.6% 2/128 • Randomization to Week 28
Musculoskeletal and connective tissue disorders ARTHRALGIA	6.1% 8/131 • Randomization to Week 28	1.6% 2/128 • Randomization to Week 28

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 1-800-821-8590

Email: genentech@druginfo.com

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 only after the first publication or presentation that involves the Overall Study. The 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