Trial Outcomes & Findings for Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy (NCT NCT00405275)

NCT ID: NCT00405275

Last Updated: 2013-12-03

Results Overview

Average difference between 48-week and Baseline DAS28. The Disease Activity Score for 28 Joints (DAS28) is a well-validated composite outcome measure ranging from 2-10 (higher scores indicating more disease) that incorporates a tender and swollen joint count of 28 joints, a laboratory measure of systemic inflammation (ESR) and a patient-reported general assessment of health on a visual analog scale (ranging from 0-10cm) all into one measure. Low disease activity is defined as DAS28 ≤ 3.2 units.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 353 participants
• Primary outcome timeframe: 48 weeks after baseline assessment
• Results posted on: 2013-12-03

Participant Flow

Bi-national, multi-center 3.5 year recruitment at 16 VA, 12 RAIN and 8 Canadian medical centers.

Participant milestones

Measure	Triple Hydroxychloroquine (400mg daily); Sulfasalazine (1g daily for 6 weeks, then increased to 2g daily; Methotrexate (maintaining baseline dose, 10-25mg weekly); Placebo, etanercept (subcutaneous injection). Nonresponders (change in DAS28 \< 1.2units at 24 weeks) were switched to Etanercept at 24 weeks. This is denoted in results table below as "switch". "No switch" participants remained on Triple therapy throughout the trial.	Etanercept Etanercept (50mg subcutaneous injections weekly); Methotrexate (maintaining baseline dose, 10-25mg weekly); Placebo, triple: placebo hydroxychloroquine (tablets daily) and placebo sulfasalazine (tablets daily). Nonresponders (change in DAS28 \< 1.2units at 24 weeks) were switched to Triple. This is denoted in results table below as "switch". "No switch" participants remained on Etanercept therapy throughout the trial.
Overall Study STARTED	178	175
Overall Study 24 Weeks (Total)	163	165
Overall Study 24 Week (no Switch)	119	121
Overall Study 24 Week (Switch)	44	44
Overall Study COMPLETED	155	156
Overall Study NOT COMPLETED	23	19

Reasons for withdrawal

Measure	Triple Hydroxychloroquine (400mg daily); Sulfasalazine (1g daily for 6 weeks, then increased to 2g daily; Methotrexate (maintaining baseline dose, 10-25mg weekly); Placebo, etanercept (subcutaneous injection). Nonresponders (change in DAS28 \< 1.2units at 24 weeks) were switched to Etanercept at 24 weeks. This is denoted in results table below as "switch". "No switch" participants remained on Triple therapy throughout the trial.	Etanercept Etanercept (50mg subcutaneous injections weekly); Methotrexate (maintaining baseline dose, 10-25mg weekly); Placebo, triple: placebo hydroxychloroquine (tablets daily) and placebo sulfasalazine (tablets daily). Nonresponders (change in DAS28 \< 1.2units at 24 weeks) were switched to Triple. This is denoted in results table below as "switch". "No switch" participants remained on Etanercept therapy throughout the trial.
Overall Study Death	1	0
Overall Study Lost to Follow-up	5	1
Overall Study Withdrawal by Subject	7	9
Overall Study Unwilling to continue	10	9

Baseline Characteristics

Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy

Baseline characteristics by cohort

Measure	Triple n=178 Participants Hydroxychloroquine, sulfasalazine and methotrexate	Etanercept n=175 Participants Etanercept and Methotrexate	Total n=353 Participants Total of all reporting groups
Age Continuous	57.8 years STANDARD_DEVIATION 13.0 • n=5 Participants	56.0 years STANDARD_DEVIATION 13.2 • n=7 Participants	56.9 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex/Gender, Customized Female	77 participants n=5 Participants	85 participants n=7 Participants	162 participants n=5 Participants
Sex/Gender, Customized Male	101 participants n=5 Participants	89 participants n=7 Participants	190 participants n=5 Participants
Sex/Gender, Customized Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	134 participants n=5 Participants	130 participants n=7 Participants	264 participants n=5 Participants
Region of Enrollment Canada	44 participants n=5 Participants	45 participants n=7 Participants	89 participants n=5 Participants

PRIMARY outcome

Timeframe: 48 weeks after baseline assessment

Population: Intention to treat analysis was performed on participants with Week 48 DAS28 data.

Average difference between 48-week and Baseline DAS28.

The Disease Activity Score for 28 Joints (DAS28) is a well-validated composite outcome measure ranging from 2-10 (higher scores indicating more disease) that incorporates a tender and swollen joint count of 28 joints, a laboratory measure of systemic inflammation (ESR) and a patient-reported general assessment of health on a visual analog scale (ranging from 0-10cm) all into one measure.

Low disease activity is defined as DAS28 ≤ 3.2 units.

Outcome measures

Measure	Triple n=154 Participants Hydroxychloroquine, sulfasalazine and methotrexate	Etanercept n=155 Participants Etanercept and Methotrexate
Mean 48-week Change in DAS28	-2.12 units on a scale Standard Deviation 1.28	-2.29 units on a scale Standard Deviation 1.30

Adverse Events

Triple

Serious events: 38 serious events

Other events: 40 other events

Deaths: 0 deaths

Etanercept

Serious events: 43 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Measure	Triple n=222 participants at risk Hydroxychloroquine, sulfasalazine and methotrexate	Etanercept n=219 participants at risk Etanercept and Methotrexate
Blood and lymphatic system disorders Anaemia	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Blood and lymphatic system disorders Lymphadenopathy	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Blood and lymphatic system disorders Retroperitoneal lymphadenopathy	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Angina unstable	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Atrial fibrillation	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Cardiac failure congestive	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	1.4% 3/219 • Number of events 3 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Coronary artery disease	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Coronary artery occlusion	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Intracardiac thrombus	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Cardiac disorders Myocardial infarction	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.91% 2/219 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Eye disorders Glaucoma	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Eye disorders Retinal detachment	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Colitis ulcerative	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Duodenitis haemorrhagic	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Dyspepsia	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Gastric ulcer	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Gastritis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Ileus	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Intestinal obstruction	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Pancreatitis acute	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
General disorders Adverse drug reaction	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
General disorders Chest discomfort	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
General disorders Chest pain	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
General disorders Non-cardiac chest pain	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Appendicitis	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Bronchitis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Bronchopulmonary aspergillosis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Cellulitis	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Clostridium difficile colitis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Diverticulitis	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Localised infection	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Lung abscess	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Pneumonia	2.3% 5/222 • Number of events 6 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	3.2% 7/219 • Number of events 7 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Tooth abscess	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Upper respiratory tract infection	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Urinary tract infection	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Viral infection	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Viral tracheitis	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Injury, poisoning and procedural complications Cardiac procedure complication	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Injury, poisoning and procedural complications Deep vein thrombosis postoperative	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Injury, poisoning and procedural complications Fall	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Injury, poisoning and procedural complications Post procedural complication	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.91% 2/219 • Number of events 3 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Investigations Catheterisation cardiac normal	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Investigations Haemoglobin decreased	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	2.7% 6/219 • Number of events 6 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer stage II	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellopontine angle tumour	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer extensive stage	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Nervous system disorders Intracranial hypotension	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Nervous system disorders Ischaemic stroke	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Nervous system disorders Transient ischaemic attack	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Psychiatric disorders Depression	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Psychiatric disorders Depression suicidal	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Psychiatric disorders Suicidal ideation	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.91% 2/219 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Bladder prolapse	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Haematuria	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Nephritic syndrome	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Nephrolithiasis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Renal failure	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Renal failure acute	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Renal and urinary disorders Urethral stenosis	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Reproductive system and breast disorders Epididymitis	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.91% 2/219 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.90% 2/222 • Number of events 2 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Skin and subcutaneous tissue disorders Angioedema	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Social circumstances Treatment noncompliance	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Surgical and medical procedures Rotator cuff repair	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Surgical and medical procedures Transurethral prostatectomy	0.45% 1/222 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.00% 0/219 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Vascular disorders Aortic dissection	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Vascular disorders Femoral arterial stenosis	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Vascular disorders Peripheral vascular disorder	0.00% 0/222 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	0.46% 1/219 • Number of events 1 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.

Other adverse events

Measure	Triple n=222 participants at risk Hydroxychloroquine, sulfasalazine and methotrexate	Etanercept n=219 participants at risk Etanercept and Methotrexate
Gastrointestinal disorders Nausea	7.2% 16/222 • Number of events 23 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	7.8% 17/219 • Number of events 18 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Nasopharyngitis	3.6% 8/222 • Number of events 8 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	6.4% 14/219 • Number of events 16 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Infections and infestations Upper respiratory tract infection	5.4% 12/222 • Number of events 17 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	8.7% 19/219 • Number of events 23 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.
Nervous system disorders Headache	7.7% 17/222 • Number of events 20 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.	6.4% 14/219 • Number of events 15 • Beginning at Informed Consent until each participant's last study follow-up contact (expected to be 48 weeks), including a period of 30 days after last contact for SAE reporting. Serious and non-serious Adverse Events are reported according to treatment at the time of event. Participants that switched therapies are represented in both treatments. Participants were seen every 6 weeks for adverse event monitoring.

Additional Information

James R. O'Dell, MD

VA Nebraska-Western Iowa Health Care System

Phone: 402-559-7288

Email: jrodell@unmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee Dr. O'Dell is an employee of the Sponsor. Dr. Edward Keystone is not. Per the signed Investigator Agreement, PIs agreed to "maintaining the confidentiality of study data and not publishing study data without prior approval of the study's Executive Committee".
• Publication restrictions are in place

Restriction type: OTHER