Trial Outcomes & Findings for A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis. (NCT NCT01988012)

NCT ID: NCT01988012

Last Updated: 2017-03-06

Results Overview

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was 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 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8\< CDAI ≤10.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 100 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2017-03-06

Participant Flow

Participant milestones

Measure	Tocilizumab Adults with rheumatoid arthritis were treated with 162 milligram (mg) tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Overall Study STARTED	100
Overall Study COMPLETED	85
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Measure	Tocilizumab Adults with rheumatoid arthritis were treated with 162 milligram (mg) tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Overall Study Adverse Event	5
Overall Study Insufficient Therapeutic Response	3
Overall Study Patient Withdrawal of Consent	4
Overall Study Lost to Follow-up	1
Overall Study Physician Decision	1
Overall Study Protocol Violation	1

Baseline Characteristics

A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis.

Baseline characteristics by cohort

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Age, Continuous	54.3 years STANDARD_DEVIATION 11.8 • n=93 Participants
Gender Female	80 Participants n=93 Participants
Gender Male	20 Participants n=93 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The analysis population included those participants from the full analysis set (FAS) for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was 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 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.

Outcome measures

Measure	Tocilizumab n=85 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity CDAI Remission	16.5 percentage of participants
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity CDAI LDA	34.1 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was 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 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in CDAI Baseline	31.89 units on a scale Standard Deviation 14.35
Change From Baseline in CDAI Change from Baseline at Week 24	-18.29 units on a scale Standard Deviation 14.52

PRIMARY outcome

Timeframe: Week 24

Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.

Outcome measures

Measure	Tocilizumab n=52 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity SDAI Remission	19.2 percentage of participants
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity SDAI LDA	38.5 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=98 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in SDAI Baseline	33.73 units on a scale Standard Deviation 14.83
Change From Baseline in SDAI Change from Baseline at Week 24	-21.41 units on a scale Standard Deviation 14.99

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=99 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) Baseline	4.98 units on a scale Standard Deviation 0.98
Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) Change from Baseline at Week 24	-2.47 units on a scale Standard Deviation 1.29

PRIMARY outcome

Timeframe: Week 24

Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).

Outcome measures

Measure	Tocilizumab n=85 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) ACR20	62.4 percentage of participants
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) ACR50	37.6 percentage of participants
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) ACR70	20.0 percentage of participants

PRIMARY outcome

Timeframe: Week 24

Population: The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'

Outcome measures

Measure

Tocilizumab n=83 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.

Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response

96.4 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in TJC and SJC TJC at Baseline	21.42 joint count Standard Deviation 15.20
Change From Baseline in TJC and SJC TJC Change from Baseline at Week 24	-11.91 joint count Standard Deviation 13.59
Change From Baseline in TJC and SJC SJC at Baseline	10.30 joint count Standard Deviation 10.27
Change From Baseline in TJC and SJC SJC Change from Baseline at Week 24	-7.54 joint count Standard Deviation 9.60

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy Baseline	26 percentage of participants
Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy Change from Baseline at Week 24	12 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) Baseline	69.73 units on a scale Standard Deviation 24.55
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) Change from Baseline at Week 24	-31.22 units on a scale Standard Deviation 28.43

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Patient Pain VAS Baseline	64.82 units on a scale Standard Deviation 26.39
Change From Baseline in Patient Pain VAS Change from Baseline at Week 24	-29.11 units on a scale Standard Deviation 29.16

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Baseline	1.55 units on a scale Standard Deviation 0.80
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Change from Baseline at Week 24	-0.34 units on a scale Standard Deviation 0.62

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change from Baseline at Week 24	6.95 units on a scale Standard Deviation 9.70
Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Baseline	23.46 units on a scale Standard Deviation 11.32

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) HDRS at Baseline	7.87 units on a scale Standard Deviation 7.19
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) HDRS at Week 24	4.94 units on a scale Standard Deviation 5.85
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) HAS at Baseline	8.56 units on a scale Standard Deviation 8.43
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) HAS at Week 24	5.93 units on a scale Standard Deviation 7.17

SECONDARY outcome

Timeframe: Up to Follow-up Week 32

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) AEs	70.0 percentage of participants
Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) AESIs	7.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Outcome measures

Measure	Tocilizumab n=100 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs % of Particpants with Dose Modifications	16 percentage of participants
Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs % of Participants Who Discontinued Study	5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24, Follow-up Week 32 and Early Withdrawal

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study

Outcome measures

Measure	Tocilizumab n=97 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies Baseline	1.0 percentage of participants
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies Week 24	0 percentage of participants
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies Follow-up Visit Week 32	0 percentage of participants
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies Early Withdrawal	0 percentage of participants

SECONDARY outcome

Timeframe: Week 12, Week 24, Follow-up Week 32 and Early Withdrawal

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Outcome measures

Measure	Tocilizumab n=91 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Immunogenicity: Tocilizumab Levels Follow-up Week 32	39.53 microgram/milliliter (mcg/mL) Standard Deviation 28.47
Immunogenicity: Tocilizumab Levels Week 12	35.49 microgram/milliliter (mcg/mL) Standard Deviation 17.81
Immunogenicity: Tocilizumab Levels Week 24	41.63 microgram/milliliter (mcg/mL) Standard Deviation 22.79
Immunogenicity: Tocilizumab Levels Early withdrawal	19.04 microgram/milliliter (mcg/mL) Standard Deviation 15.69

SECONDARY outcome

Timeframe: Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal

Population: The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

A positive change from Week 1 indicates an increase in sIL-6R levels.

Outcome measures

Measure	Tocilizumab n=98 Participants Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels Week 1	38.33 nanograms/milliliter (ng/mL) Standard Deviation 10.30
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels Change from Week 1 at Week 12	475.79 nanograms/milliliter (ng/mL) Standard Deviation 120.98
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels Change from Week 1 at Week 24	503.67 nanograms/milliliter (ng/mL) Standard Deviation 127.13
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels Change from Week 1 at Follow-up at Week 32	382.26 nanograms/milliliter (ng/mL) Standard Deviation 240.95
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels Change from Week 1 at Early withdrawal	309.91 nanograms/milliliter (ng/mL) Standard Deviation 183.07

Adverse Events

Tocilizumab

Serious events: 6 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab n=100 participants at risk Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Gastrointestinal disorders Colitis	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
General disorders Chest pain	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Cellulitis	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Reproductive system and breast disorders Adnexal torsion	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Skin and subcutaneous tissue disorders Urticaria	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Vascular disorders Haematoma	1.0% 1/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Other adverse events

Measure	Tocilizumab n=100 participants at risk Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended.
Blood and lymphatic system disorders Leukopenia	11.0% 11/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Blood and lymphatic system disorders Neutropenia	12.0% 12/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Upper respiratory tract infection	7.0% 7/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Urinary tract infection	7.0% 7/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Investigations Alanine aminotransferase increased	8.0% 8/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Investigations Aspartate aminotransferase increased	6.0% 6/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
Investigations Hepatic enzyme increased	11.0% 11/100 • Up to Follow-up Week 32 The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 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