- Revised study objectives to specify subjects should be naïve to biologic therapies and clarified how study drug was to be referenced - Specified how study drug dosing was transitioned from Part 1 to Part 2 and from Part 2 to OLSES - Inclusion and exclusion criteria were edited to better define the selection of the study population - Clarified removal of subjects from therapy or assessment - Clarified treatments administered, selection, and timing of doses in study - Specified blind was to be maintained until last subject completed Part 2 - Added details regarding study drug dispensing - Clarified prior and concomitant medications - Explained serum samples regarding treatment compliance - Added instructions for dosing subjects in Part 2 - Specified requirement to assess all previous injection sites at all visits after Day 0 - Added further specification and explanation regarding primary efficacy variables (ACR20, 66/68 SJC/TJC, CRP, HAQ-DI, subject’s pain assessment, SGA, and PGA) - Added instructions for calculating DAS28-CRP(4) and explained scores - Defined response duration variables for Part 2 - Added respiratory rate to vital sign measurements and clarified methods and timing of vital signs and electrocardiogram assessments - Clarified use for and retention of serum samples - Specified analyses to be performed by local and central laboratories - Defined the PK Concentration Population and described use of serum samples for PK analysis - Added details regarding Data Safety Monitoring Board evaluation at end of Part 1

- Added instruction that subjects who discontinue study drug for any reason during Part 1 should return for all Part 1 study visits per protocol - Inclusion and exclusion criteria were edited to better define the selection of the study population: added approved kinase inhibitors as DMARDs; added that subjects with recent known exposure to a patient with TB should be excluded; added that patients with an indeterminate QuantiFERON-TB Gold test could be rescreened 1 time and if a negative result, the subject could participate in the study; and added that male subjects whose partners may become pregnant or who may breastfeed during the study are not eligible to participate - Clarified removal of subjects from therapy or assessment - Revised handling of used syringes and specified subjects were not required to bring unused syringes to each visit - Clarified that oral corticosteroids and methotrexate doses could be reduced during the study for safety considerations only - Clarified ISRs regarding first dose of study drug and reporting as an “ISR” adverse event - Specified that if the subject’s normal dosing schedule coincides with a study visit the subject should be reminded to hold their dose until after the study visit - Added that the online DAS28-CRP(4) calculator was provided to sites by Medpace - Clarified QuantiFERON-TB Gold test screening and chest x-ray

- Clarified that joints injected at screening will not be calculated in the screening joint count assessment but will be included in the baseline joint count assessment - Clarified that joints injected during Part 2 will not be eliminated in subsequent joint counts but should be noted as swollen and tender - Inclusion and exclusion criteria were edited to better define the selection of the study population: removed CRP criteria from the definition of active disease and added DAS28-CRP(4) as an inclusion criterion; added abstinence as an allowable form of birth control for women of childbearing potential; clarified that other disease processes, not only evidence of TB, demonstrated on abnormal chest x-ray would exclude subjects; also clarified that a chest x-ray should be obtained during screening if one is not available with in the previous 6 months; and clarified possible regional infections that may be covered by regional guidelines - Added that a positive QuantiFERON-TB Gold test at any time during the study is cause for termination of the subject from the study - Added that females using abstinence as birth control will have a urine pregnancy test at each study visit; also added for Argentina only that females of childbearing potential and not surgically sterile will have a monthly urine pregnancy test - Clarified instructions for subject disposal of used syringes - Clarified that baseline labs did not need to be repeated if screening labs were drawn within 2 weeks prior to baseline visit - Added clarification for recording ISRs as adverse events

Excluded Japan. - Removed language that 200 subjects had to complete Part 2 for the Part 1 database to be cleaned and locked and that the Data Safety Monitoring Board had to meet after the last subject completes the 24-week evaluations during Part 1 - Prohibited administration of a live vaccine within 4 weeks prior to screening - Specified that study drug syringes were to be inspected by study personnel prior to dispensation - Revised for consistency that a steroid injection for a single joint at or after Week 24 should be noted as swollen and tender going forward - Updated testing methods for positive HIV results

- Added information defining when subjects should have returned for their Follow-up Visit in relation to when they discontinued study drug - Revised text throughout to reflect the decision to offer OLSES in selected countries - Specified that for subjects who were taking leflunomide, cholestyramine should have been administered to facilitate excretion of leflunomide 2 weeks prior to screening - Clarified the requirements for the use of abstinence as a means of birth control - Clarified the TB testing entry criteria and what results permitted a repeat test - Increased sample size to account for the number of subjects who were randomized prior to study drug suspension - Clarified use of a topical NSAID as an allowed NSAID - Added verbiage to comply with Japanese Society of Hematology guidelines for management of hepatitis B - Specified that subjects were to bring back all unused study drug at their Week 24 Visit - Added definition for unexpected adverse events - Added that adverse event outcomes were to be recorded by the Investigator - Clarified Sponsor reporting requirements of serious adverse events and/or suspected unexpected serious adverse events - Updated analysis plan based on study drug dosing suspension - Specified that Population 1 and Population 2 were to be analyzed separately - Revised definitions of Full Analysis and Safety Populations and Japanese Population based on study drug dosing suspension - Clarified restrictions for administration of live vaccines to be within 4 week prior to screening or at any time during the course of the study