Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) \[visual analogue scale (VAS) with values from 0=best to 100=worst\], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)\]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the Intent-to-Treat (ITT) set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at 0 (no pain) and 100 (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at 0 (no pain) and 100 (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at 0 (no pain) and 100 (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (PtGA and PhGA VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

CDAI total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

CDAI total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 4. Week 4 is not pre-specified time point to report.

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 4. Week 4 is not pre-specified time point to report.

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 4. Week 4 is not pre-specified time point to report.

Blood samples were collected for the assessment of fasting lipid profile including triglycerides. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 24

Population: Blood samples were collected at indicated time points per schedule of activities in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.

Blood samples were collected for the assessment of fasting lipid profile including triglycerides. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1) and Week 52

Population: The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP and GH).The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring of SF-36.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits. CB=subtracting PD visit value from BV. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Only those participants with data available at the specified time points were analyzed.

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF), bodily pain(BP), role limitations due to physical and emotional problems, general health(GH), mental health(MH), social functioning(SF), vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified time points were analyzed.

The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the specified time points were analyzed.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains (PF,role-physical,BP,GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the ITT set that inlcude all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time frame: Baseline (Week 12), Week 24 and Week 52

Population: The analysis was performed on the Safety Set-Placebo switch. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time frame: Baseline (Day 1), Week 24 and Week 52

Population: The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Baseline (Day 1) and Week 12

Population: The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

Concentrations of GM-CSF autoantibodies were determined.

Time frame: At baseline

Population: The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified time points were analyzed.

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) \<= 1, Swollen Joint Count 66 (SJC66) \<= 1, high sensitivity C-reactive Protein (hsCRP) \<= 1mg/dl and patient's global assessment of disease activity (PtGA) \<= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Only those participants with data available at the specified time points were analyzed.

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) \<= 1, Swollen Joint Count 66 (SJC66) \<= 1, high sensitivity C-reactive Protein (hsCRP) \<= 1mg/dl and patient's global assessment of disease activity (PtGA) \<= 10.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified time points were analyzed.

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) \<= 1, Swollen Joint Count 66 (SJC66) \<= 1, high sensitivity C-reactive Protein (hsCRP) \<= 1mg/dl and patient's global assessment of disease activity (PtGA) \<= 10.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the specified time points were analyzed.

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Time frame: Up to Week 59

Population: The analysis was performed on the Safety Set for Pooled Placebo (collected data till Week 12), GSK3196165 90 mg + MTX, GSK3196165 150 mg + MTX, Tofacitinib 5 mg + MTX (collected data till Week 59).

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included.

Time frame: Up to Week 59

Population: The analysis was performed on Safety Set-Placebo switch for Placebo + MTX and GSK3196165 90 mg + MTX, Placebo + MTX and GSK3196165 150 mg + MTX, Placebo + MTX and Tofacitinib 5 mg + MTX (collected data from Week 12 to 59).

Serum samples were collected for the determination of anti- GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.

Time frame: Up to Week 59

Population: The analysis was performed on the Safety set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified time points were analyzed.

Number of participants with NCI-CTCAE \>=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case \>=Grade 3 shifts from Baseline. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Time frame: Up to Week 59

Population: The analysis was performed on the Safety Set for Pooled Placebo (collected data till Week 12), GSK3196165 90 mg + MTX, GSK3196165 150 mg + MTX, Tofacitinib 5 mg + MTX (collected data till Week 59).

Number of participants with NCI-CTCAE \>=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case \>=Grade 3 shifts from Baseline.

Time frame: Up to Week 59

Population: The analysis was performed on Safety Set-Placebo switch for Placebo + MTX and GSK3196165 90 mg + MTX, Placebo + MTX and GSK3196165 150 mg + MTX, Placebo + MTX and Tofacitinib 5 mg + MTX (collected data from Week 12 to 59).

ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) \[visual analogue scale (VAS) with values from 0=best to 100=worst\], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)\].

Time frame: Week 24

Population: The analysis was performed on the ITT set that includes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the subject was randomized to. Analysis was performed using multiple imputation method to handle missing data.

ACR50/70 is calculated as a 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) \[VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)\]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) \[VAS with values from 0=best to 100=worst\], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein mg/L (hsCRP)\].

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) \[VAS with values from 0=best to 100=worst\], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein mg/L (hsCRP)\].

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; if current DAS28 \<=3.2 and DAS28 decrease from Baseline (\>1.2: good response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response); if current DAS28 \>3.2 to \<=5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response) and if current DAS28 \>5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: no response) and (\<=0.6: no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; if current DAS28 \<=3.2 and DAS28 decrease from Baseline (\>1.2: good response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response); if current DAS28 \>3.2 to \<=5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response) and if current DAS28 \>5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: no response) and (\<=0.6: no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at given time point was defined based on the combination of current DAS28 score and improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 \<=3.2 and DAS28 decrease from Baseline (\>1.2:good response), (\>0.6 to \<=1.2:moderate response) and (\<=0.6:no response); DAS28 \>3.2 to \<=5.1 and DAS28 decrease from Baseline (\>1.2:moderate response), (\>0.6 to \<=1.2:moderate response) and (\<=0.6:no response) and DAS28 \>5.1 and DAS28 decrease from Baseline (\>1.2:moderate response), (\>0.6 to \<=1.2:no response) and (\<=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (\<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP \<2.6. A negative change from baseline in DAS28-CRP indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP \<2.6. A negative change from baseline in DAS28-CRP indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP\<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP\<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter \[mm\]/hour\[hr\]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR\<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR \<2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR \<2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR \<2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter \[mm\]/hour\[hr\]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR\<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter \[mm\]/hour\[hr\]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR\<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (\<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of \<=0.5.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of \<=0.5.

Time frame: Week 24 and Week 52

Population: The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of \<=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time frame: Week 12

Population: The analysis was performed on the ITT set that inlcudes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the subject was randomized to. Analysis was performed using multiple imputation method to handle missing data.