Trial Outcomes & Findings for A Long-term Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients With Rheumatoid Arthritis (NCT NCT00721123)

NCT ID: NCT00721123

Last Updated: 2013-11-28

Results Overview

The number of participants experiencing at least one adverse event (AE) is recorded for each 12-month time period, with multiple occurrences in a single individual counted. Because months were calculated as 28 days, the periods actually equate to 48 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 538 participants
• Primary outcome timeframe: through 264 Weeks
• Results posted on: 2013-11-28

Participant Flow

Participant milestones

Measure	Tocilizumab 8 mg/kg Patients received tocilizumab (TCZ) 8 mg/kg intravenously every 4 weeks.
Overall Study STARTED	538
Overall Study COMPLETED	355
Overall Study NOT COMPLETED	183

Reasons for withdrawal

Measure	Tocilizumab 8 mg/kg Patients received tocilizumab (TCZ) 8 mg/kg intravenously every 4 weeks.
Overall Study Adverse Event	96
Overall Study Death	10
Overall Study Insufficient Therapeutic Response	21
Overall Study Protocol Violation	1
Overall Study Refused Treatment	41
Overall Study Failure to Return	9
Overall Study Withdrawal by Subject	5

Baseline Characteristics

A Long-term Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Tocilizumab 8 mg/kg n=538 Participants Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
Age Continuous	50.8 years STANDARD_DEVIATION 12.03 • n=5 Participants
Sex: Female, Male Female	443 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants

PRIMARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.

The number of participants experiencing at least one adverse event (AE) is recorded for each 12-month time period, with multiple occurrences in a single individual counted. Because months were calculated as 28 days, the periods actually equate to 48 weeks.

Outcome measures

Measure	Months 0 - 12 n=538 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=509 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=463 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=434 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=414 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 Participants with scores at 264 weeks post-baseline.
Adverse Event (AE) Summary Over Time Experienced an adverse event	433 Participants	390 Participants	333 Participants	294 Participants	329 Participants	—
Adverse Event (AE) Summary Over Time Experienced a serious adverse event	55 Participants	55 Participants	55 Participants	35 Participants	74 Participants	—
Adverse Event (AE) Summary Over Time Experienced AE leading to withdrawal	24 Participants	17 Participants	22 Participants	8 Participants	32 Participants	—

PRIMARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.

Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. Patient year rates with confidence interval were calculated for adverse events of interest in evaluating the long-term safety of the product being studied.

Abbreviations include the following: adverse event (AE), adverse event of special interest (AESI), gastrointestinal (GI), serious adverse event (SAE), and investigational product (IP). Hypersensitivity events were defined as AEs that occurred during or within 24 hours of IP infusion and were not deemed "unrelated" to trial treatment by the investigator. This definition includes all types of AEs, regardless of whether or not they were consistent with hypersensitivity.

Medical confirmation of the AESI "GI perforation" was based on medical adjudication of events captured by the GI Perforation Standardised MedDRA Queries (SMQs).

Outcome measures

Measure	Months 0 - 12 n=538 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=509 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=463 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=434 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=414 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 Participants with scores at 264 weeks post-baseline.
Summary Adverse Event Rates Over Time Total AE rate	393.76 Adverse Events per 100 Patient Years Interval 376.32 to 411.8	286.17 Adverse Events per 100 Patient Years Interval 270.66 to 302.34	260.14 Adverse Events per 100 Patient Years Interval 244.78 to 276.22	249.84 Adverse Events per 100 Patient Years Interval 234.36 to 266.07	212.04 Adverse Events per 100 Patient Years Interval 201.62 to 222.86	—
Summary Adverse Event Rates Over Time Total SAE rate	12.54 Adverse Events per 100 Patient Years Interval 9.59 to 16.11	13.05 Adverse Events per 100 Patient Years Interval 9.91 to 16.87	18.74 Adverse Events per 100 Patient Years Interval 14.79 to 23.42	12.62 Adverse Events per 100 Patient Years Interval 9.34 to 16.69	13.12 Adverse Events per 100 Patient Years Interval 10.62 to 16.02	—
Summary Adverse Event Rates Over Time Rate for AEs leading to withdrawal	5.14 Adverse Events per 100 Patient Years Interval 3.33 to 7.59	3.82 Adverse Events per 100 Patient Years Interval 2.23 to 6.12	5.35 Adverse Events per 100 Patient Years Interval 3.36 to 8.11	2.06 Adverse Events per 100 Patient Years Interval 0.89 to 4.06	4.37 Adverse Events per 100 Patient Years Interval 2.99 to 6.17	—
Summary Adverse Event Rates Over Time AESI All Infections	92.94 Adverse Events per 100 Patient Years Interval 84.57 to 101.92	87.52 Adverse Events per 100 Patient Years Interval 79.03 to 96.66	87.36 Adverse Events per 100 Patient Years Interval 78.56 to 96.88	87.32 Adverse Events per 100 Patient Years Interval 78.27 to 97.12	72.82 Adverse Events per 100 Patient Years Interval 66.77 to 79.27	—
Summary Adverse Event Rates Over Time AESI Serious Infections	3.29 Adverse Events per 100 Patient Years Interval 1.88 to 5.34	2.47 Adverse Events per 100 Patient Years Interval 1.24 to 4.43	5.60 Adverse Events per 100 Patient Years Interval 3.55 to 8.4	3.35 Adverse Events per 100 Patient Years Interval 1.78 to 5.73	3.55 Adverse Events per 100 Patient Years Interval 2.32 to 5.2	—
Summary Adverse Event Rates Over Time AESI Opportunistic infections	0 Adverse Events per 100 Patient Years There were no opportunistic infections in this period.	0.22 Adverse Events per 100 Patient Years Interval 0.01 to 1.25	0 Adverse Events per 100 Patient Years There were no opportunistic infections in this period.	0.52 Adverse Events per 100 Patient Years Interval 0.06 to 1.86	0.27 Adverse Events per 100 Patient Years Interval 0.03 to 0.99	—
Summary Adverse Event Rates Over Time AESI Hypersensitivity events	27.35 Adverse Events per 100 Patient Years Interval 22.9 to 32.41	9.90 Adverse Events per 100 Patient Years Interval 7.19 to 13.29	5.35 Adverse Events per 100 Patient Years Interval 3.36 to 8.11	3.86 Adverse Events per 100 Patient Years Interval 2.16 to 6.37	4.10 Adverse Events per 100 Patient Years Interval 2.77 to 5.85	—
Summary Adverse Event Rates Over Time AESI Hepatic events	0.41 Adverse Events per 100 Patient Years Interval 0.05 to 1.49	0.90 Adverse Events per 100 Patient Years Interval 0.25 to 2.3	0.49 Adverse Events per 100 Patient Years Interval 0.06 to 1.76	1.03 Adverse Events per 100 Patient Years Interval 0.28 to 2.64	0.68 Adverse Events per 100 Patient Years Interval 0.22 to 1.59	—
Summary Adverse Event Rates Over Time AESI Myocardial infarction	0.62 Adverse Events per 100 Patient Years Interval 0.13 to 1.8	0 Adverse Events per 100 Patient Years There were no myocardial infarctions in this period.	0.24 Adverse Events per 100 Patient Years Interval 0.01 to 1.36	0.77 Adverse Events per 100 Patient Years Interval 0.16 to 2.26	0.27 Adverse Events per 100 Patient Years Interval 0.03 to 0.99	—
Summary Adverse Event Rates Over Time AESI Stroke, ischemic or hemorrhagic	0.21 Adverse Events per 100 Patient Years Interval 0.01 to 1.15	0.22 Adverse Events per 100 Patient Years Interval 0.01 to 1.25	0.73 Adverse Events per 100 Patient Years Interval 0.15 to 2.13	0.26 Adverse Events per 100 Patient Years Interval 0.01 to 1.44	0.41 Adverse Events per 100 Patient Years Interval 0.08 to 1.2	—
Summary Adverse Event Rates Over Time AESI GI perforation	0 Adverse Events per 100 Patient Years There were no medically confirmed GI perforations in this period.	0 Adverse Events per 100 Patient Years There were no medically confirmed GI perforations in this period.	0.49 Adverse Events per 100 Patient Years Interval 0.06 to 1.76	0.26 Adverse Events per 100 Patient Years Interval 0.01 to 1.44	0 Adverse Events per 100 Patient Years There were no medically confirmed GI perforations in this period.	—
Summary Adverse Event Rates Over Time AESI Malignancy	1.23 Adverse Events per 100 Patient Years Interval 0.45 to 2.69	1.80 Adverse Events per 100 Patient Years Interval 0.78 to 3.55	0.97 Adverse Events per 100 Patient Years Interval 0.27 to 2.49	0.77 Adverse Events per 100 Patient Years Interval 0.16 to 2.26	1.50 Adverse Events per 100 Patient Years Interval 0.75 to 2.69	—
Summary Adverse Event Rates Over Time AESI Demyelinating disorders	0.21 Adverse Events per 100 Patient Years Interval 0.01 to 1.15	0 Adverse Events per 100 Patient Years There were no demyelinating disorders in this period.	0 Adverse Events per 100 Patient Years There were no demyelinating disorders in this period.	0 Adverse Events per 100 Patient Years There were no demyelinating disorders in this period.	0 Adverse Events per 100 Patient Years There were no demyelinating disorders in this period.	—
Summary Adverse Event Rates Over Time AESI Serious bleeding disorders	0.62 Adverse Events per 100 Patient Years Interval 0.13 to 1.8	0.45 Adverse Events per 100 Patient Years Interval 0.05 to 1.63	0.49 Adverse Events per 100 Patient Years Interval 0.06 to 1.76	0.26 Adverse Events per 100 Patient Years Interval 0.01 to 1.44	0.68 Adverse Events per 100 Patient Years Interval 0.22 to 1.59	—

PRIMARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which included all participants who entered the study and received at least one dose of tocilizumab at any time.

Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1.

To calculate the death rate, the total cumulative number of years that all participants were exposed to the drug, from first active drug intake to last safety assessment available + 1, was calculated as 2461.94. Since 10 participants died during that time, the death rate per year was not informative (0.00). Therefore, the overall death rate was calculated with the confidence interval based on events per 100 patient years exposure.

Outcome measures

Measure	Months 0 - 12 n=538 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 Participants with scores at 264 weeks post-baseline.
Overall Death Rate Over Time	0.41 Deaths per 100 PY Interval 0.19 to 0.75	—	—	—	—	—

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab, with a score at the given time point.

The American College of Rheumatology (ACR) established certain criteria to measure improvement in rheumatoid arthritis symptoms that include tender or swollen joint counts and five other criteria, including acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire.

Clinical trials use the ACR Score, based on those criteria, as a standard for reporting different degrees of improvement in rheumatoid arthritis symptoms.

Scores on the ACR scale may be up to ACR100 because the number after "ACR" is the percent of improvement in tender or swollen joint counts as well as in three of the other five criteria. Clinical trials determine the percentage of participants who achieve that score - that percentage of improvement.

Outcome measures

Measure	Months 0 - 12 n=522 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=480 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=422 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=413 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=387 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=367 Participants Participants with scores at 264 weeks post-baseline.
Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks ACR20	63.2 Percentage of Participants	76.0 Percentage of Participants	81.2 Percentage of Participants	83.3 Percentage of Participants	82.2 Percentage of Participants	83.9 Percentage of Participants
Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks ACR50	41.2 Percentage of Participants	50.6 Percentage of Participants	58.1 Percentage of Participants	59.6 Percentage of Participants	62.5 Percentage of Participants	67.8 Percentage of Participants
Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks ACR70	17.4 Percentage of Participants	27.1 Percentage of Participants	38.2 Percentage of Participants	41.9 Percentage of Participants	42.1 Percentage of Participants	45.8 Percentage of Participants
Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks ACR90	4.8 Percentage of Participants	5.2 Percentage of Participants	11.3 Percentage of Participants	15.3 Percentage of Participants	16.8 Percentage of Participants	19.3 Percentage of Participants

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.

The disease activity score 28 (DAS28) is a combined index for measuring disease activity in rheumatic arthritis (RA) that includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The DAS28 scale ranges from 0 to 10, where lower scores represent less disease activity. Participants with DAS28 scores less than 2.6 were categorized as responders with remission and those with DAS 28 scores of 3.2 or less were categorized as responders with low disease activity (LDA). The percentage of participants classified as responders in each category was recorded over time.

Outcome measures

Measure	Months 0 - 12 n=516 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=470 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=430 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=410 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=381 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=363 Participants Participants with scores at 264 weeks post-baseline.
Percentage of Participants Classified as Responders by Disease Activity Scores Over Time, Through 264 Weeks Responders with Remission (DAS<2.6)	24.6 Percentage of Participants	43.0 Percentage of Participants	53.7 Percentage of Participants	54.9 Percentage of Participants	57.2 Percentage of Participants	60.6 Percentage of Participants
Percentage of Participants Classified as Responders by Disease Activity Scores Over Time, Through 264 Weeks Responders with Low Disease Activity (DAS</= 3.2)	41.7 Percentage of Participants	57.7 Percentage of Participants	67.0 Percentage of Participants	71.2 Percentage of Participants	70.6 Percentage of Participants	72.2 Percentage of Participants

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.

Participants were classified as responders based on a European League Against Rheumatism (EULAR) response of Good or Moderate. Comparing the DAS28 from one patient on two different time points, it is possible to define improvement or response. The EULAR response criteria take into consideration both the first score and the change in score in order to classify them as good response, moderate response or no response. The percentage of participants who were classified as responders was recorded, as posted below.

Outcome measures

Measure	Months 0 - 12 n=514 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=468 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=429 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=409 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=380 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=362 Participants Participants with scores at 264 weeks post-baseline.
Percentage of Participants Classified as Responders by EULAR Response Over Time, Through 264 Weeks EULAR Good Response	41.2 Percentage of Participants	56.6 Percentage of Participants	65.5 Percentage of Participants	70.9 Percentage of Participants	69.5 Percentage of Participants	71.0 Percentage of Participants
Percentage of Participants Classified as Responders by EULAR Response Over Time, Through 264 Weeks EULAR Moderate Response	48.1 Percentage of Participants	39.1 Percentage of Participants	29.8 Percentage of Participants	25.9 Percentage of Participants	26.8 Percentage of Participants	25.1 Percentage of Participants

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

Swollen joint count (SJC) includes an assessment of 66 joints, and tender joint count (TJC) include an assessment of 68 joints. Joint prosthesis, arthrodesis or fused joints were not considered. Joints were assessed and classified as swollen/not swollen, and tender/not tender, by pressure and joint manipulation on physical examination. Change from Baseline in the SJC and TJC were calculated at given time points, and a negative change indicates improvement.

A small proportion of participants in the all-exposure population reduced or stopped their oral corticosteroid use due to sustained efficacy (defined as at least a 50% improvement in both swollen joint count (SJC) and tender joint count (TJC).

Outcome measures

Measure	Months 0 - 12 n=532 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=506 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=454 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=422 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=405 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=371 Participants Participants with scores at 264 weeks post-baseline.
Change From Baseline in Scores for Swollen and Tender Joint Counts Over Time, Through 264 Weeks Swollen Joint Count (SJC)	-11.7 Joints Standard Deviation 11.50	-13.6 Joints Standard Deviation 11.04	-15.6 Joints Standard Deviation 11.51	-16.2 Joints Standard Deviation 11.46	-16.2 Joints Standard Deviation 11.48	-16.5 Joints Standard Deviation 11.26
Change From Baseline in Scores for Swollen and Tender Joint Counts Over Time, Through 264 Weeks Tender Joint Count (TJC)	-17.4 Joints Standard Deviation 14.82	-20.3 Joints Standard Deviation 15.12	-23.1 Joints Standard Deviation 15.82	-23.8 Joints Standard Deviation 16.14	-23.8 Joints Standard Deviation 15.89	-24.8 Joints Standard Deviation 16.37

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

The Stanford Health Assessment Questionnaire - Disability Index (HAQ-DI) is a questionnaire specific for rheumatoid arthritis with 8 component sets (domains): dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has 2-3 questions (for a total of 20) that participants answer with categorical answers enumerated as a scale of 0-3, where 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.

To calculate the HAQ-DI the patient must have a domain score for at least 6 of the eight domains. The HAQ-DI is the sum of the domain scores, divided by the number of domains that have a score (in range 6-8). The resulting HAQ-DI scores are on a scale that ranges from 0 to 3, where 0=lowest level of difficulty and 3=highest level of difficulty. A negative change from baseline indicates improvement.

Outcome measures

Measure	Months 0 - 12 n=445 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=408 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=376 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=349 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=332 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=316 Participants Participants with scores at 264 weeks post-baseline.
Change From Baseline in Scores for Health Assessment Questionnaire - Disability Index Over Time, Through 264 Weeks	-0.49 Units on a Scale Standard Deviation 0.582	-0.53 Units on a Scale Standard Deviation 0.614	-0.59 Units on a Scale Standard Deviation 0.636	-0.61 Units on a Scale Standard Deviation 0.655	-0.65 Units on a Scale Standard Deviation 0.661	-0.62 Units on a Scale Standard Deviation 0.693

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

Patient's global assessment of disease activity is the patient's overall assessment of their disease activity during specified time periods on a 100 mm horizontal visual analogue scale (VAS). The left-hand extreme of the line was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme as "maximum disease activity" (maximum arthritis disease activity). Change from baseline was calculated for given periods, and a negative change indicates improvement.

Outcome measures

Measure	Months 0 - 12 n=521 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=479 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=442 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=414 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=387 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=367 Participants Participants with scores at 264 weeks post-baseline.
Change From Baseline in Scores for Patient's Global Assessment of Disease Activity Over Time, Through 264 Weeks	-26.6 Units on a Scale Standard Deviation 26.87	-30.3 Units on a Scale Standard Deviation 27.71	-31.1 Units on a Scale Standard Deviation 27.65	-31.6 Units on a Scale Standard Deviation 26.74	-33.0 Units on a Scale Standard Deviation 26.83	-32.9 Units on a Scale Standard Deviation 27.58

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

Physician's global assessment of disease activity is the treating physician's assessment of the patient's current disease activity on a 100 mm horizontal visual analogue scale (VAS). The extreme left end of the line was described as "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end as "maximum disease activity". Change from baseline was calculated for given periods, and a negative change indicates improvement.

Outcome measures

Measure	Months 0 - 12 n=521 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=479 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=439 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=416 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=389 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=369 Participants Participants with scores at 264 weeks post-baseline.
Change From Baseline in Scores for Physician's Global Assessment of Disease Activity Over Time, Through 264 Weeks	-33.8 Units on a Scale Standard Deviation 23.33	-38.1 Units on a Scale Standard Deviation 23.77	-41.1 Units on a Scale Standard Deviation 23.79	-43.2 Units on a Scale Standard Deviation 23.26	-44.8 Units on a Scale Standard Deviation 22.66	-44.4 Units on a Scale Standard Deviation 23.64

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

The patient's assessment of the patient's current level of pain on a 100 mm horizontal VAS was recorded. The extreme left end of the line was described as "no pain" and the extreme right end as "unbearable pain". Change from baseline was calculated for given periods, and a negative change indicates improvement.

Outcome measures

Measure	Months 0 - 12 n=521 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=479 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=442 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=414 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=388 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=367 Participants Participants with scores at 264 weeks post-baseline.
Change From Baseline in Scores for Patient's Level of Pain Over Time, Through 264 Weeks	-23.7 Units on a Scale Standard Deviation 26.38	-26.7 Units on a Scale Standard Deviation 27.27	-28.0 Units on a Scale Standard Deviation 26.33	-28.1 Units on a Scale Standard Deviation 25.99	-29.5 Units on a Scale Standard Deviation 26.98	-29.2 Units on a Scale Standard Deviation 26.84

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

Quality of life is measured using the sub-scale for Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). The assessment was originally developed for chronic illnesses and is now widely used for patients with rheumatoid arthritis.

FACIT-F is a 13-item questionnaire. Participants score each item on a 5-point scale: 0 (Not at all) to 4 (Very much), for a highest possible score of 52. The responses are transformed into a FACIT-F score, where a higher score reflects an improvement. The percentage of participants with at least a 5-point improvement from baseline in the Facit-F score is shown at categorical time points.

Outcome measures

Measure	Months 0 - 12 n=523 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=482 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=444 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=414 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=390 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=370 Participants Participants with scores at 264 weeks post-baseline.
Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Measure for Fatigue Over Time, Through 264 Weeks	66.0 Percentage of Participants	58.7 Percentage of Participants	61.5 Percentage of Participants	62.3 Percentage of Participants	60.0 Percentage of Participants	62.2 Percentage of Participants

SECONDARY outcome

Timeframe: through 264 Weeks

Population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.

The SF-36 Health Survey is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL. The percentage of participants with at least a 5-point improvement from baseline is presented for each subscale.

Outcome measures

Measure	Months 0 - 12 n=423 Participants Participants with scores during Months 0-12, which equates to baseline through Week 48.	Months 13 - 24 n=424 Participants Participants with scores during Months 13 - 24, which equates to Weeks 49-96.	Months 25 - 36 n=395 Participants Participants with scores during Months 25 - 36, which equates to Weeks 97-144.	Months 37 - 48 n=373 Participants Participants with scores during Months 37 - 48, which equates to Weeks 145-192.	Months Greater Than 48 n=344 Participants Participants with scores during Months greater than 48, which equates to Weeks 193-264.	Week 264 n=334 Participants Participants with scores at 264 weeks post-baseline.
Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Using the 36-Item Short-Form Health Survey (SF-36) Over Time, Through 264 Weeks SF-36 MCS	48.2 Percentage of Participants	46.2 Percentage of Participants	48.6 Percentage of Participants	49.9 Percentage of Participants	49.7 Percentage of Participants	49.1 Percentage of Participants
Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Using the 36-Item Short-Form Health Survey (SF-36) Over Time, Through 264 Weeks SF-36 PCS	63.8 Percentage of Participants	69.1 Percentage of Participants	71.1 Percentage of Participants	71.3 Percentage of Participants	73.3 Percentage of Participants	71.3 Percentage of Participants

Adverse Events

Tocilizumab 8 mg/kg

Serious events: 199 serious events

Other events: 475 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab 8 mg/kg n=538 participants at risk Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
Infections and infestations Pneumonia	2.2% 12/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Diverticulitis	0.93% 5/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Cellulitis	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Erysipelas	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Gastroenteritis	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Abscess limb	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Bronchopneumonia	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Sepsis	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Urinary tract infection	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Cellulitis staphylococcal	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Herpes zoster	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Pneumonia pneumococcal	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Postoperative wound infection	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Pulmonary tuberculosis	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Respiratory tract infection	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Sinusitis	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Subcutaneous abscess	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Varicella	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Abscess neck	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Appendicitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Arthritis bacterial	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Bronchitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Bursitis infective staphylococcal	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Douglas' abscess	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Endocarditis staphylococcal	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Gastrointestinal infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Helicobacter gastritis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Intervertebral discitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Lobar pneumonia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Lung Abscess	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Mediastinitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Osteomyelitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Peritonitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Peritonsillar abscess	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Post procedural infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Proteus infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Pulmonary sepsis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Pyelonephritis acute	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Septic arthritis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Staphylococcal septic shock	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Soft tissue infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Tuberculosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Tuberculous pleurisy	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Upper respiratory tract infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Wound infection	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the cervix	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage II	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage III	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage II	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma stage III	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer metastatic	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage III	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic squamous cell carcinoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer metastatic	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage I	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer stage III	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer state unspecified	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Femoral neck fracture	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Femur fracture	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Ankle fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Contusion	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Dislocation of vertebra	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Fractured ischium	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Gas poisoning	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Hand fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Hip fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Incision site haematoma	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Joint injury	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Laceration	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Lower limb fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Meniscus lesion	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Overdose	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Periprosthetic fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Post procedural complication	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Postoperative fever	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Radius fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Tendon rupture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Tibia fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Upper limb fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Vascular bypass dysfunction	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Wound dehiscence	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Injury, poisoning and procedural complications Wrist fracture	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Inguinal hernia	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Gastritis	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Abdominal pain upper	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Diarrhoea	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Diverticular perforation	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Pancreatitis	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Abdominal pain	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Anal fistula	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Constipation	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Crohn's disease	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Flatulence	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Glossitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Large intestinal ulcer	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Melaena	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Oesophageal perforation	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Pancreatitis acute	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Rectal haemorrhage	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Umbilical hernia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 6/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Back pain	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Foot deformity	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Lupus-like syndrome	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Muscle necrosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Muscular weakness	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Pain in extremity	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Acute myocardial infarction	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Atrial fibrillation	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Acute coronary syndrome	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Angina unstable	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Coronary artery disease	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Myocardial infarction	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Supraventricular tachycardia	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Arteriosclerosis coronary artery	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Atrioventricular block complete	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Cardiac failure	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Cardiac failure congestive	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Cardio-respiratory arrest	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Dressler's syndrome	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Supraventricular extrasystoles	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Cardiac disorders Tachyarrhythmia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Sciatica	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Carpal tunnel syndrome	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Cerebral ischaemia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Dyskinesia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Essential tremor	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Haemorrhagic stroke	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Headache	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Hypertensive encephalopathy	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Hypoaesthesia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Migraine	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Nerve root compression	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Presyncope	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Syncope	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Thrombotic cerebral infarction	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Tremor	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Hypertension	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Vericose vein	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Deep vein thrombosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Hypertensive crisis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Iliac artery occlusion	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Orthostatic hypotension	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Peripheral arterial occlusive disease	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Vasculitis necrotising	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Hepatobiliary disorders Cholecystitis	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Hepatobiliary disorders Cholelithiasis	0.74% 4/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Hepatobiliary disorders Cholecystitis acute	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Hepatobiliary disorders Cholecystitis chronic	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Hepatobiliary disorders Perforation bile duct	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Emphysema	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Mediastinal haemorrhage	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Rheumatoid lung	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Confusional state	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Adjustment disorder	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Anxiety	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Delirium	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Major depression	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Schizophrenia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Suicide attempt	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Ovarian cyst	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Uterine haemorrhage	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Endometriosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Female genital tract fistula	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Uterine polyp	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Reproductive system and breast disorders Uterine prolapse	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
General disorders Device breakage	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
General disorders Device dislocation	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
General disorders Non-cardiac chest pain	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
General disorders Chest pain	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Actinic keratosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Angioedema	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Cutaneous vasculitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Erythema	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Blood and lymphatic system disorders Anaemia	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Blood and lymphatic system disorders Anaemia of chronic disease	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Blood and lymphatic system disorders Iron deficiency anaemia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Renal and urinary disorders Calculus urinary	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Renal and urinary disorders Nephrolithiasis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Renal and urinary disorders Renal colic	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Renal and urinary disorders Urinary incontinence	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.56% 3/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Eye disorders Cataract	0.37% 2/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Eye disorders Ulcerative keratitis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Immune system disorders Allergy to arthropod bite	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Immune system disorders Anaphylactic reaction	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Immune system disorders Sarcoidosis	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Ear and labyrinth disorders Sudden hearing loss	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Ear and labyrinth disorders Vertigo	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Endocrine disorders Goitre	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Metabolism and nutrition disorders Hypokalaemia	0.19% 1/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.

Other adverse events

Measure	Tocilizumab 8 mg/kg n=538 participants at risk Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
Infections and infestations Upper respiratory tract infection	25.3% 136/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Nasopharyngitis	24.7% 133/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Urinary tract infection	17.3% 93/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Bronchitis	15.4% 83/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Gastroenteritis	12.8% 69/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Pharyngitis	11.2% 60/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Influenza	8.0% 43/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Oral herpes	6.9% 37/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Sinusitis	5.9% 32/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Infections and infestations Rhinitis	5.8% 31/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Diarrhoea	15.8% 85/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Dyspepsia	15.8% 85/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Nausea	9.3% 50/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Gastritis	6.5% 35/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Abdominal pain	5.9% 32/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Abdominal pain upper	5.9% 32/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Mouth ulceration	5.4% 29/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.2% 28/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Back pain	11.9% 64/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	11.9% 64/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Musculoskeletal and connective tissue disorders Arthralgia	6.9% 37/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Headache	16.5% 89/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Nervous system disorders Dizziness	6.5% 35/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Vascular disorders Hypertension	19.9% 107/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Investigations Alanine aminotransferase increased	11.0% 59/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Investigations Transaminases increased	9.5% 51/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Cough	8.6% 46/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.9% 32/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Depression	8.0% 43/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Psychiatric disorders Insomnia	5.6% 30/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Metabolism and nutrition disorders Hypercholesterolaemia	6.1% 33/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Blood and lymphatic system disorders Leukopenia	5.8% 31/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Skin and subcutaneous tissue disorders Rash	5.6% 30/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Ear and labyrinth disorders Vertigo	5.0% 27/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
Eye disorders Conjunctivitis	5.0% 27/538 All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Results disclosure agreements

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

Restriction type: OTHER