Trial Outcomes & Findings for A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor (NCT NCT01283971)

NCT ID: NCT01283971

Last Updated: 2014-02-10

Results Overview

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. DAS28 Remission is defined as a DAS28 score \<2.6.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 96 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2014-02-10

Participant Flow

Participant milestones

Measure	Adalimumab + Methotrexate Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Overall Study STARTED	48	48
Overall Study Intent to Treat Population	46	48
Overall Study COMPLETED	33	36
Overall Study NOT COMPLETED	15	12

Reasons for withdrawal

Measure	Adalimumab + Methotrexate Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Overall Study Adverse Event	3	5
Overall Study Insufficient therapeutic responses	3	3
Overall Study Protocol Violation	5	1
Overall Study Refused treatment	3	1
Overall Study Failure to return	0	1
Overall Study Administrative reasons	1	1

Baseline Characteristics

A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor

Baseline characteristics by cohort

Measure	Adalimumab + Methotrexate n=48 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Total n=96 Participants Total of all reporting groups
Age, Continuous	54.3 years STANDARD_DEVIATION 11.89 • n=5 Participants	51.3 years STANDARD_DEVIATION 12.51 • n=7 Participants	52.8 years STANDARD_DEVIATION 12.2 • n=5 Participants
Age, Customized <50 years	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Age, Customized 50 to 64 years	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Age, Customized ≥65 to 75 years	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Age, Customized >75 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	38 Participants n=7 Participants	78 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. DAS28 Remission is defined as a DAS28 score <2.6.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24	30.3 Percentage of participants	36.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 24	66.7 Percentage of participants	62.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With ACR50 Response at Week 24	24.2 Percentage of participants	42.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With ACR70 Response at Week 24	18.2 Percentage of participants	22.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other EULAR components were used as observed.

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total score ranges from 0 (best) to 10 (worst). A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24 Moderate Response	39.4 Percentage of participants	27.8 Percentage of participants
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24 Good Response	30.3 Percentage of participants	58.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. LDAS is defined as DAS28 ≤3.2.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Percentage of Participants With DAS28 Low Disease Activity (LDAS) at Week 24	30.3 Percentage of participants	58.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in DAS28 Score at Week 24	-1.65 Score on a scale Standard Deviation 1.541	-2.80 Score on a scale Standard Deviation 1.553

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation was used to impute missing swollen joint counts.

66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=46 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Swollen Joint Count (SJC) at Week 24	-5.7 Joint count Standard Deviation 7.56	-11.3 Joint count Standard Deviation 15.84

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation carried forward was used to impute missing tender joint counts.

68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=46 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Tender Joint Count (TJC) at Week 24	-8.0 Joint count Standard Deviation 14.62	-13.9 Joint count Standard Deviation 16.50

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) at Week 24	-30.1 Score on a scale Standard Deviation 20.57	-23.8 Score on a scale Standard Deviation 29.28

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The patient's global assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in the Patient Global Assessment of Disease Activity VAS at Week 24	-30.2 Score on a scale Standard Deviation 22.17	-21.5 Score on a scale Standard Deviation 28.89

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in the Physician Global Assessment of Disease Activity VAS at Week 24	-37.0 Score on a scale Standard Deviation 23.20	-36.8 Score on a scale Standard Deviation 32.34

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The concentration of CRP was measured in milligram/liter (mg/L). A reduction in the level is considered an improvement

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Week 24	-1.127 mg/L Standard Deviation 11.1261	-7.474 mg/L Standard Deviation 10.8446

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeter/hour (mm/hr). A reduction in the level is considered an improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=33 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=36 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24	-1.2 mm/hr Standard Deviation 16.78	-25.7 mm/hr Standard Deviation 25.52

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=30 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24	-0.19 Score on a scale Standard Deviation 0.437	-0.36 Score on a scale Standard Deviation 0.543

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicates improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=32 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=34 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score at Week 24	5.6 Score on a scale Standard Deviation 9.60	8.0 Score on a scale Standard Deviation 9.33

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=29 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=33 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Quality of Life Short Form (SF-36) Score at Week 24 Physical Component Summary Score	4.39 Score on a scale Standard Deviation 6.110	5.84 Score on a scale Standard Deviation 7.980
Change From Baseline in Quality of Life Short Form (SF-36) Score at Week 24 Mental Component Summary Score	6.07 Score on a scale Standard Deviation 12.171	6.84 Score on a scale Standard Deviation 11.907

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

RAPID3 is a patient self reported assessment that combines the HAQ-DI [20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions answered on a 4-point scale where 0=without any difficulty to 3=unable to do} converted to a score of 0-10, the Patients Assessment of Pain [Over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain] converted to a score of 0-10 and the Patient's Global Assessment of Disease Activity [over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity] converted to a score of 0-10. The 3 individual scales are summed for a raw score of 0-30 which is divided by 3 to achieve a total possible adjusted score of 0-10. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Adalimumab + Methotrexate n=30 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Week 24	-2.17 Score on a scale Standard Deviation 1.611	-1.83 Score on a scale Standard Deviation 2.257

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with hemoglobin data available at Baseline and Week 24.

Blood was collected at Baseline and Week 24. The samples were sent to a central laboratory for Hemoglobin analysis reported in gram/deciliter (g/dL). A positive number change from Baseline (a higher hemoglobin level compared to Baseline) indicated improvement

Outcome measures

Measure	Adalimumab + Methotrexate n=32 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=35 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Change From Baseline in Hemoglobin at Week 24	1.2 g/dL Standard Deviation 8.70	6.5 g/dL Standard Deviation 12.01

SECONDARY outcome

Timeframe: 32 weeks

Population: Safety Population included all participants who received study drug and who had at least 1 post-dose safety assessment.

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Measure	Adalimumab + Methotrexate n=48 Participants Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 Participants Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths Any Adverse Event (AE)	35 Participants	33 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths Any Serious Adverse Event	2 Participants	8 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths AE leading to withdrawal	3 Participants	5 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths Death	0 Participants	0 Participants

Adverse Events

Adalimumab + Methotrexate

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Tocilizumab + Methotrexate

Serious events: 8 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Adalimumab + Methotrexate n=48 participants at risk Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 participants at risk Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Infections and infestations Pneumonia	2.1% 1/48	2.1% 1/48
Infections and infestations Appendicitis	0.00% 0/48	2.1% 1/48
Infections and infestations Bursitis infective	0.00% 0/48	2.1% 1/48
Infections and infestations Urinary tract infection	0.00% 0/48	2.1% 1/48
Injury, poisoning and procedural complications Hip fracture	0.00% 0/48	2.1% 1/48
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/48	2.1% 1/48
Investigations Alanine aminotransferase increased	2.1% 1/48	0.00% 0/48
Investigations Transaminases increased	0.00% 0/48	2.1% 1/48
Cardiac disorders Ventricular tachycardia	0.00% 0/48	2.1% 1/48
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/48	2.1% 1/48
Psychiatric disorders Depression	0.00% 0/48	2.1% 1/48
Skin and subcutaneous tissue disorders Rash	0.00% 0/48	2.1% 1/48

Other adverse events

Measure	Adalimumab + Methotrexate n=48 participants at risk Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.	Tocilizumab + Methotrexate n=48 participants at risk Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
Infections and infestations Upper respiratory tract infection	12.5% 6/48	6.2% 3/48
Infections and infestations Nasopharyngitis	12.5% 6/48	2.1% 1/48
Infections and infestations Bronchitis	6.2% 3/48	4.2% 2/48
Infections and infestations Gastroenteritis	2.1% 1/48	6.2% 3/48
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 4/48	0.00% 0/48
Respiratory, thoracic and mediastinal disorders Cough	6.2% 3/48	0.00% 0/48
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	4.2% 2/48	6.2% 3/48
Nervous system disorders Headache	2.1% 1/48	6.2% 3/48

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

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