Trial Outcomes & Findings for A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis (NCT NCT01655381)

Last Updated: 2017-01-31

Results Overview

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect in a neonate/infant or significant medical event in the Investigator's judgment. AE of special interest (AESI) includes serious and/or medically significant infectious; myocardial infarction(MI) / acute coronary syndrome (ACS); gastrointestinal (GI) perforation; anaphylaxis / hypersensitivity reactions; demyelinating disorders; stroke; serious and/or medically significant bleeding events; serious and/or medically significant hepatic events; malignancies malignant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

15 participants

Primary outcome timeframe

Up to 160 weeks

Results posted on

2017-01-31

Participant Flow

A total 15 participants who completed the Week 104 visit of the WA19926 core study, were enrolled in this follow-up open-label extension study.

Participant milestones

Participant milestones
Measure	Tocilizumab Tocilizumab 8 milligrams per kilogram (mg/kg) administered intravenously once every 4 weeks during a minimum of 104 weeks.
Overall Study STARTED	15
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Tocilizumab 8 milligrams per kilogram (mg/kg) administered intravenously once every 4 weeks during a minimum of 104 weeks.
Overall Study Investigator Decision	1
Overall Study Moved to Another City	1
Overall Study Insufficient Treatment Response	1

Baseline Characteristics

A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Age, Continuous	54.8 years STANDARD_DEVIATION 9.1 • n=5 Participants
Gender Female	12 Participants n=5 Participants
Gender Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 160 weeks

Population: Safety population is defined as all included participants who received having at least one tocilizumab administration.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With Any Adverse Event (AE) AE	93.3 percentage of participants
Percentage of Participants With Any Adverse Event (AE) SAE	6.7 percentage of participants
Percentage of Participants With Any Adverse Event (AE) Non-serious AE	93.3 percentage of participants
Percentage of Participants With Any Adverse Event (AE) Tocilizumab-related AE	80.0 percentage of participants
Percentage of Participants With Any Adverse Event (AE) Tocilizumab-related SAE	0 percentage of participants
Percentage of Participants With Any Adverse Event (AE) Tocilizumab-related non-SAE	80.0 percentage of participants
Percentage of Participants With Any Adverse Event (AE) AESI	20.0 percentage of participants
Percentage of Participants With Any Adverse Event (AE) Tocilizumab-related AESI	20.0 percentage of participants
Percentage of Participants With Any Adverse Event (AE) AE leading to dose modification	33.3 percentage of participants
Percentage of Participants With Any Adverse Event (AE) AE leading to Tocilizumab discontinuation	6.7 percentage of participants
Percentage of Participants With Any Adverse Event (AE) AE leading to death	0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Clinical remission: Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) less than (\<)2.6 and/or Simplified Disease Activity Index (SDAI) less than or equal to (≤)3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0-10, with higher scores corresponding to greater disease activity. SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0-86, where lower scores indicate less disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With at Least One Clinical Remission Period	100.0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Drug-free remission period was defined as clinical remission for at least 2 consecutive assessment visits (every 12 weeks) AND without tocilizumab administration during this clinical remission period.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With at Least One Drug-Free Period	13.3 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Clinical remission was defined as DAS28-ESR \<2.6 and/or SDAI ≤3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity. SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Cumulative Time of Remission Per Participant Over the Extension Study Period	598.00 days Interval 179.0 to

SECONDARY outcome

Timeframe: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

An RA flare was defined as an increase in DAS28-ESR from the previous available visits of \>1.2, or \>0.6 if current DAS28-ESR ≥3.2. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With at Least 1 Rheumatoid Arthritis (RA) Flare	40.0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Time to RA flare was defined as period of clinical remission or drug-free remission followed by flare of DAS28-ESR (increase in DAS28-ESR from the previous available visits of \>1.2, or \>0.6 if current DAS28-ESR ≥3.2). In the case of several remission periods for the same participant, the largest period was used.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Time to RA Flare Following Remission or Drug-Free Remission	289.0 days Interval 179.0 to 739.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Change From Day 1 in DAS28-ESR Scores Over Time Day 1 (n = 14)	2.09 units on a scale Standard Deviation 1.12
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 12 (n = 10)	-0.43 units on a scale Standard Deviation 0.96
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 104 (n = 10)	-0.94 units on a scale Standard Deviation 1.44
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 116 (n = 6)	-1.15 units on a scale Standard Deviation 1.37
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 24 (n = 13)	-0.65 units on a scale Standard Deviation 1.86
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 36 (n = 11)	-0.03 units on a scale Standard Deviation 1.42
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 48 (n = 13)	-0.58 units on a scale Standard Deviation 1.46
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 56 (n = 11)	-1.02 units on a scale Standard Deviation 1.50
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 68 (n = 11)	-1.39 units on a scale Standard Deviation 1.31
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 80 (n = 10)	-0.83 units on a scale Standard Deviation 1.33
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 92 (n = 10)	-0.69 units on a scale Standard Deviation 1.50
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 128 (n = 2)	0.40 units on a scale Standard Deviation 1.70
Change From Day 1 in DAS28-ESR Scores Over Time Change at Week 140 (n = 1)	0.10 units on a scale Standard Deviation NA Standard deviation was not estimable as 1 participant was evaluated.

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), and the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 36 (n = 0)	NA units on a scale Standard Deviation NA Mean and standard deviation was not estimable as no participants was evaluated.
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 48 (n = 3)	-3.70 units on a scale Standard Deviation 3.21
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Day 1 (n = 6)	4.40 units on a scale Standard Deviation 3.67
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 12 (n = 6)	-1.70 units on a scale Standard Deviation 3.43
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 24 (n = 4	2.68 units on a scale Standard Deviation 17.12
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 56 (n = 3)	-2.90 units on a scale Standard Deviation 1.64
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 68 (n = 2)	-7.30 units on a scale Standard Deviation 3.54
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 80 (n = 3)	-3.37 units on a scale Standard Deviation 3.42
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 92 (n = 4)	-2.05 units on a scale Standard Deviation 5.11
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 104 (n = 2)	-6.10 units on a scale Standard Deviation 0.14
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 116 (n = 3)	-4.77 units on a scale Standard Deviation 2.46
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 128 (n = 0)	NA units on a scale Standard Deviation NA Mean and standard deviation was not estimable as no participants was evaluated.
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time Change at Week 140 (n = 1)	-0.90 units on a scale Standard Deviation NA Standard deviation was not estimable as 1 participant was evaluated.

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 tender joints. Higher scores correspond to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 140 (n = 1)	-1.00 tender joints Standard Deviation NA Standard deviation was not estimable as 1 participant was evaluated.
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Day 1 (n = 15)	2.07 tender joints Standard Deviation 5.62
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 12 (n = 15)	-0.87 tender joints Standard Deviation 6.58
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 24 (n = 14)	0.29 tender joints Standard Deviation 9.22
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 36 (n = 14)	1.00 tender joints Standard Deviation 8.68
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 48 (n = 14)	1.07 tender joints Standard Deviation 9.24
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 56 (n = 13)	-1.77 tender joints Standard Deviation 6.26
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 68 (n = 12)	-1.42 tender joints Standard Deviation 5.92
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 80 (n = 11)	-2.45 tender joints Standard Deviation 6.67
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 92 (n = 12)	-0.67 tender joints Standard Deviation 3.75
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 104 (n = 11)	-1.82 tender joints Standard Deviation 7.05
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 116 (n = 6)	-1.00 tender joints Standard Deviation 0.89
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time Change at Week 128 (n = 3)	0.67 tender joints Standard Deviation 2.08

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 swollen joints. Higher scores correspond to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Day 1 (n = 15)	0.33 swollen joints Standard Deviation 0.62
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 128 (n = 3)	0.00 swollen joints Standard Deviation 0.00
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 140 (n = 1)	0.00 swollen joints Standard Deviation NA Standard deviation was not estimable as 1 participant was evaluated.
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 12 (n = 15)	0.27 swollen joints Standard Deviation 1.44
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 24 (n = 14)	0.50 swollen joints Standard Deviation 2.03
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 36 (n = 14)	1.50 swollen joints Standard Deviation 2.71
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Chnage at Week 48 (n = 14)	0.29 swollen joints Standard Deviation 1.38
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 56 (n = 13)	0.46 swollen joints Standard Deviation 2.07
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 68 (n = 12)	-0.08 swollen joints Standard Deviation 1.16
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 80 (n = 11)	0.09 swollen joints Standard Deviation 1.38
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 92 (n = 12)	0.50 swollen joints Standard Deviation 2.35
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 104 (n = 11)	0.55 swollen joints Standard Deviation 1.86
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time Change at Week 116 (n = 6)	-0.17 swollen joints Standard Deviation 1.72

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. Higher scores correspond to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Erythrocyte Sedimentation Rate (ESR) Over Time Day 1 (n = 14)	10.0 mm/hour Interval 1.0 to 61.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 12 (n = 11)	2.00 mm/hour Interval 1.0 to 20.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 24 (n = 14)	2.50 mm/hour Interval 1.0 to 24.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 36 (n = 12)	2.00 mm/hour Interval 1.0 to 26.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 48 (n = 14)	2.00 mm/hour Interval 1.0 to 19.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 56 (n = 13)	2.00 mm/hour Interval 1.0 to 9.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 68 (n = 12)	2.50 mm/hour Interval 1.0 to 13.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 80 (n = 11)	3.00 mm/hour Interval 2.0 to 6.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 92 (n = 11)	2.00 mm/hour Interval 1.0 to 20.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 104 (n = 11)	2.00 mm/hour Interval 1.0 to 30.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 116 (n= 6)	2.00 mm/hour Interval 2.0 to 15.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 128 (n= 3)	3.00 mm/hour Interval 2.0 to 4.0
Erythrocyte Sedimentation Rate (ESR) Over Time Week 140 (n= 1)	10.00 mm/hour Interval 10.0 to 10.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5 milligrams per liter (mg/L). Higher scores correspond to greater disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
C-reactive Protein (CRP) Level Day 1 (n = 6)	4.70 mg/L Interval 0.5 to 24.0
C-reactive Protein (CRP) Level Week 12 (n = 11)	2.00 mg/L Interval 0.3 to 10.0
C-reactive Protein (CRP) Level Week 24 (n = 11)	2.00 mg/L Interval 0.2 to 9.0
C-reactive Protein (CRP) Level Week 36 (n = 6)	0.85 mg/L Interval 0.3 to 2.0
C-reactive Protein (CRP) Level Week 48 (n = 8)	1.30 mg/L Interval 0.2 to 5.0
C-reactive Protein (CRP) Level Week 56 (n = 9)	2.00 mg/L Interval 0.2 to 21.0
C-reactive Protein (CRP) Level Week 68 (n = 7)	2.00 mg/L Interval 0.5 to 12.0
C-reactive Protein (CRP) Level Week 80 (n = 8)	2.00 mg/L Interval 0.3 to 10.7
C-reactive Protein (CRP) Level Week 92 (n = 8)	2.00 mg/L Interval 0.3 to 25.0
C-reactive Protein (CRP) Level Week 104 (n = 7)	2.00 mg/L Interval 0.3 to 22.5
C-reactive Protein (CRP) Level Week 116 (n= 4)	2.00 mg/L Interval 2.0 to 3.0
C-reactive Protein (CRP) Level Week 128 (n= 1)	2.00 mg/L Interval 2.0 to 2.0
C-reactive Protein (CRP) Level Week 140 (n= 1)	4.00 mg/L Interval 4.0 to 4.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

The participants' global assessment of pain (VAS) was assessed using a 100-mm horizontal VAS with 0=no pain to 100=maximum pain.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Participants' Global Assessment of Pain (VAS) Score Day 1 (n = 15)	11.00 units on a scale Interval 0.0 to 50.0
Participants' Global Assessment of Pain (VAS) Score Week 12 (n = 15)	7.00 units on a scale Interval 0.0 to 37.0
Participants' Global Assessment of Pain (VAS) Score Week 24 (n = 14)	9.00 units on a scale Interval 0.0 to 75.0
Participants' Global Assessment of Pain (VAS) Score Week 36 (n = 14)	10.00 units on a scale Interval 0.0 to 66.0
Participants' Global Assessment of Pain (VAS) Score Week 48 (n = 14)	8.00 units on a scale Interval 0.0 to 64.0
Participants' Global Assessment of Pain (VAS) Score Week 56 (n = 13)	4.00 units on a scale Interval 0.0 to 50.0
Participants' Global Assessment of Pain (VAS) Score Week 68 (n = 12)	4.00 units on a scale Interval 0.0 to 25.0
Participants' Global Assessment of Pain (VAS) Score Week 80 (n = 11)	19.00 units on a scale Interval 1.0 to 40.0
Participants' Global Assessment of Pain (VAS) Score Week 92 (n = 12)	8.50 units on a scale Interval 0.0 to 50.0
Participants' Global Assessment of Pain (VAS) Score Week 104 (n = 11)	9.00 units on a scale Interval 0.0 to 24.0
Participants' Global Assessment of Pain (VAS) Score Week 116 (n= 6)	3.50 units on a scale Interval 0.0 to 20.0
Participants' Global Assessment of Pain (VAS) Score Week 128 (n= 3)	3.00 units on a scale Interval 1.0 to 20.0
Participants' Global Assessment of Pain (VAS) Score Week 140 (n= 1)	6.00 units on a scale Interval 6.0 to 6.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

The participants' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Participants' Global Assessment of Disease Activity (VAS) Score Week 92 (n = 12)	10.50 units on a scale Interval 0.0 to 30.0
Participants' Global Assessment of Disease Activity (VAS) Score Day 1 (n = 15)	13.00 units on a scale Interval 0.0 to 30.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 12 (n = 15)	17.00 units on a scale Interval 0.0 to 75.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 24 (n = 14)	18.50 units on a scale Interval 0.0 to 80.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 36 (n = 14)	10.00 units on a scale Interval 0.0 to 68.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 48 (n = 14)	7.50 units on a scale Interval 0.0 to 49.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 56 (n = 13)	5.00 units on a scale Interval 0.0 to 50.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 68 (n = 12)	5.00 units on a scale Interval 0.0 to 32.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 80 (n = 11)	24.00 units on a scale Interval 1.0 to 70.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 104 (n = 11)	10.00 units on a scale Interval 0.0 to 57.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 116 (n= 6)	4.00 units on a scale Interval 0.0 to 15.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 128 (n= 3)	7.00 units on a scale Interval 2.0 to 10.0
Participants' Global Assessment of Disease Activity (VAS) Score Week 140 (n= 1)	15.00 units on a scale Interval 15.0 to 15.0

SECONDARY outcome

Timeframe: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

The physicians' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Physicians' Global Assessment of Disease Activity (VAS) Score Week 48 (n = 14)	5.00 units on a scale Interval 0.0 to 50.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 56 (n = 13)	6.00 units on a scale Interval 0.0 to 60.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 68 (n = 12)	4.50 units on a scale Interval 0.0 to 13.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 80 (n = 11)	3.00 units on a scale Interval 0.0 to 18.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 92 (n = 12)	9.0 units on a scale Interval 0.0 to 43.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 104 (n = 11)	5.00 units on a scale Interval 0.0 to 40.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 116 (n= 6)	5.00 units on a scale Interval 0.0 to 10.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 128 (n= 3)	15.00 units on a scale Interval 1.0 to 30.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 140 (n= 1)	5.00 units on a scale Interval 5.0 to 5.0
Physicians' Global Assessment of Disease Activity (VAS) Score Day 1 (n = 15)	5.00 units on a scale Interval 0.0 to 20.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 12 (n = 15)	6.00 units on a scale Interval 0.0 to 21.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 24 (n = 13)	1.00 units on a scale Interval 0.0 to 60.0
Physicians' Global Assessment of Disease Activity (VAS) Score Week 36 (n = 14)	5.00 units on a scale Interval 0.0 to 55.0

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128 140

HAQ-DI remission was defined as HAQ-DI score \<0.5. HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Baseline (n = 15)	73.3 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 12 (n = 9)	66.7 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 80 (n = 9)	66.7 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 92 (n = 8)	75.0 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 104 (n = 7)	71.4 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 116 (n= 3)	100 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 128 (n= 1)	100 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 140 (n= 1)	100 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 24 (n = 8)	62.5 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 36 (n = 10)	60.0 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 48 (n = 10)	50.0 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 56 (n = 10)	60.0 percentage of participants
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission Week 68 (n = 9)	77.8 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22. HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Outcome measures

Outcome measures
Measure	Tocilizumab n=15 Participants Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 12 (n = 9)	33.3 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 48 (n = 10)	30.0 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 68 (n = 9)	33.3 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 80 (n = 9)	22.2 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 24 (n = 8)	25.0 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 36 (n = 10)	40.0 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 56 (n = 10)	30.0 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 92 (n = 8)	12.5 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 104 (n = 7)	28.6 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 116 (n= 3)	100 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 128 (n= 1)	100 percentage of participants
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI Week 140 (n= 1)	100 percentage of participants

Adverse Events

Tocilizumab

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab n=15 participants at risk Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
General disorders Oedema peripheral	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.

Other adverse events

Other adverse events
Measure	Tocilizumab n=15 participants at risk Tocilizumab 8 mg/kg administered intravenously once every 4 weeks during a minimum of 104 weeks.
Infections and infestations Bronchitis	40.0% 6/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Gastroenteritis	26.7% 4/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Nasopharyngitis	26.7% 4/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Oral herpes	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Pharyngitis	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Tracheitis	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Urinary tract infection	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Ear infection	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Fungal infection	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Gingivitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Laryngitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Periodontitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Pertussis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Rhinitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Sinusitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Tonsillitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Tooth abscess	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Tracheobronchitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Infections and infestations Vulvovaginal mycotic infection	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Back pain	33.3% 5/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Arthralgia	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Neck pain	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Tendon pain	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Arthritis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Metatarsalgia	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Tendon disorder	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Musculoskeletal and connective tissue disorders Tendonitis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
General disorders Asthenia	26.7% 4/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
General disorders Chest pain	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
General disorders Fatigue	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
General disorders Inflammatory pain	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Dermatitis contact	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Dermatosis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Dry skin	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Ecchymosis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Intertrigo	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Photosensitivity reaction	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Pruritus generalised	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Skin and subcutaneous tissue disorders Rash pruritic	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Alanine aminotransferase increased	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Colonoscopy	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Hepatic enzyme increased	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Interferon gamma release assay positive	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Transaminases increased	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Investigations Weight decreased	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Psychiatric disorders Insomnia	20.0% 3/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Psychiatric disorders Depression	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Psychiatric disorders Anxiety	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Gastrointestinal disorders Diarrhoea	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Gastrointestinal disorders Anal fissure	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Gastrointestinal disorders Constipation	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Gastrointestinal disorders Dental caries	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Injury, poisoning and procedural complications Limb injury	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Injury, poisoning and procedural complications Tooth avulsion	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Injury, poisoning and procedural complications Tooth fracture	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Metabolism and nutrition disorders Hypertriglyceridaemia	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Metabolism and nutrition disorders Decreased appetite	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Respiratory, thoracic and mediastinal disorders Lung disorder	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Blood and lymphatic system disorders Neutropenia	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Blood and lymphatic system disorders Normochromic normocytic anaemia	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Renal and urinary disorders Haematuria	13.3% 2/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Surgical and medical procedures Cataract operation	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Surgical and medical procedures Dental cleaning	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Surgical and medical procedures Eye laser surgery	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Surgical and medical procedures Joint injection	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Surgical and medical procedures Tooth extraction	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Ear and labyrinth disorders Tympanic membrane disorder	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Ear and labyrinth disorders Vertigo	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Eye disorders Eyelid oedema	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Hepatobiliary disorders Cholelithiasis	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Immune system disorders Allergy to arthropod bite	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.
Nervous system disorders Radicular pain	6.7% 1/15 • Up to 160 weeks An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population, defined as all included participants having at least one tocilizumab administration.

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but 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