Added urinalysis at Week 52 and fixed study day for follow up visit; Asia region was split to Japan and (South Korea + Taiwan) for randomization stratification; decreased entry methotrexate dose to 6 mg/week from 8 mg/week in geographic regions where 6 mg/week was a recommended initial dose by local guidance or standard of care; removed permission for use of any second disease modifying anti-rheumatic drug (DMARD) therapy, including sulfasalazine and/or anti-malarial drug during trial, and 4-week washout was required; Added recording of injection times after pharmacokinetic (PK) samples, and added time to 1 other injection before Week 12 primary endpoint that would not otherwise be recorded; added additional anti-drug antibody (ADA) sample at Week 6 as requested by the European Medicines Agency (EMA); changed ADA analysis plan to run all samples in both ADA assays as requested by the US Food and Drug Administration (FDA); added a return visit at Week 26 in subjects who withdrew before Week 26, as requested by the FDA; added follow-up telephone calls at Weeks 4 and 8 in subjects who withdrew before that, as requested by the EMA; added the option for an additional safety visit including laboratories at the discretion of the investigator, in case of any significant safety concerns at a phone follow-up, as requested by the EMA; updated permitted opioid drug tables to specify types of opioids allowed as background therapies versus those allowed as rescue therapies.

Added safety telephone follow-up contact 16 weeks after final dose of study drug; added exclusion of subjects with prior history of severe allergic or anaphylactic reaction to a biologic drug, and clarified the washout period for prior investigational drugs to be the longer of the 2 stated options (4 weeks or 5 half-lives); pregnancy was added to treatment withdrawal criteria; added clarification and cross-references placed in protocol.

Changed immunogenicity testing plan so that all immunogenicity samples were to be tested for ADA using a single, validated electrochemiluminescent (ECL) immunoassay for ADA against PF-06410293, instead of 2 assays; added another ADA sample, with a companion PK sample, in both treatment period 2(TP2) and TP3 for monitoring of post switch immunogenicity time course; modified follow-up procedures for subjects who discontinued before Week 26 to require more on-site visits in TP1; modified wording for subject discontinuation due to lack of efficacy to allow some investigator discretion; specified requirements for immediate release narcotic; added supplemental urine pregnancy testing as requested by Canadian regulatory authorities.

Added DMARDs to the DMARD Washout Periods table.

Modified optional isoniazid prophylaxis for high-risk subjects to be globally available where standard of care during adalimumab (study drug) treatment; added an appendix describing additional GCP and inspection responsibilities; clarified that the subject would select the most appropriate form of birth control in consultation with the investigator or designee; corrected the End of Treatment (EOT)/Early Termination (ET) urine pregnancy test to occur on Week 78/Visit 18 and not during Visit 17 at Week 76; clarified maximal paracetamol dose for chronic dosing (comparable to maximal chronic acetaminophen dose already listed); for RA flare treatment, added 1 oral corticosteroid (7 day) course after study Week 26 and altered the maximal intra articular corticosteroid dose to 40 mg methylprednisolone (or equivalent) per injection.

Added a prefilled pen (PFP) sub-study during TP3 to evaluate the success of PF-06410293 administration by PFP.