An AE was any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Number of participants with any nSAE or SAE are presented.

Safety Population comprised of all participants who received at least one dose of the study treatment.

Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 millimoles per liter(mmol/L), alkaline phosphatase(high): >=2*ULN U/L, AST(high): >=2*ULN U/L, calcium: <2(low) or >2.75 mmol/L(high), creatinine (high): increase from Baseline >44.25 mmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5*ULN micromoles per liter(µmol/L). Participants were counted in the worst case category if their value changes (to low or to high), unless there is no change in their category. Only those clinical chemistry parameters with PCI values (to low and to high) have been presented.

Safety Population

Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs). PCI ranges were < 0.075 (decrease from baseline) or >0.54 proportion of red blood cells in blood (high) for hematocrit, <25 (low) or >180 grams per liter (g/L) (high) for hemoglobin, <0.8 x10^9 cells per liter (cells/L) for lymphocytes (low), <100 (low) or >550 x10^9 cells/L(high) for platelets, <1.5 x10^9 cells/L (low) for total neutrophils and < 3 (low) or >20 x10^9 cells/L (high) for WBCs. Participants were counted in the worst case category that their value changes (to low or to high), unless there is no change in their category. Only those hematology parameters with PCI values (to low and to high) have been presented.

Safety Population

Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with worst case any increase from Baseline values are presented.

Safety Population

Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. Microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for hyaline casts, red blood cells and white blood cells. Results for microscopy parameters hyaline casts, red blood cells and white blood cells were categorized as 'any increase from Baseline', which imply any increase in their count in the urine sample. Only participants with worst case any increase from Baseline values are presented.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval, QT interval corrected for heart rate according to either Bazett's formula (QTcB) and QT interval corrected for heart rate according to Fridericia's formula (QTcF). ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval QTcB and QTcF. ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Vital sign-heart rate was planned to be assessed as a measure of safety and tolerability.

The data for assessment of vital sign-heart rate was not collected.

Blood samples were collected on Day 8 and Day 43 for determining pre-dose plasma concentrations of GSK2982772. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Pharmacokinetic GSK298772 Population comprised of participants in the safety population who received an active dose and for whom a GSK2982772 pharmacokinetic sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected on Day 1, Day 8 and Day 43 for determining post-dose plasma concentrations of GSK2982772. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Pharmacokinetic GSK298772 Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected to evaluate plasma concentration of GSK2982772. Pharmacokinetic parameters including trough plasma concentration was determined using standard non-compartmental methods.

Pharmacokinetic GSK298772 Population. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected on Day 1, Day 8 and Day 43 for determining pre-dose plasma concentrations of methotrexate. Pharmacokinetic parameters were determined using standard non-compartmental methods. Only participants who received methotrexate during the study were included.

Pharmacokinetic Methotrexate Population comprised of participants in the safety population who received an active dose and for whom a methotrexate pharmacokinetic sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

CRP is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of CRP. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

IL6 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of IL6. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

MMP-1, MMP-3, and MMP-13 are an inflammatory biomarkers present in blood. Blood samples were collected at indicated time points for the assessment of MMP-1, MMP-3, and MMP-13. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

TIMP-1 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of TIMP-1. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

MCP-1 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MCP-1. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

MIF is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MIF. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

MRP8/14 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MRP8/14. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value].

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone erosions. Individual location scores range from 0 (no erosions) to 10 (91 to 100 percent of bone eroded) based on the proportion of eroded bone compared to the "assessed bone volume" on all available images. The final bone erosion score was the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 250, with 0 implying no bone erosion and 250 implying 91 to 100 percent bone eroded. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

RAMRIQ bone erosions (normalized) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the volume of bone erosions divided by sum of the individual measurements of the bone volume. The total score ranged from 0 to 1, with 0 implying no erosive damage. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Change from Baseline in bone erosions was planned to be assessed by modified CARLOS.

Safety Population. Data was not collected for this outcome measure, as bone erosion is not a part of modified CARLOS. Bone erosion was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 23 and 24, respectively.

A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

RAMRIQ synovitis (normalised) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the volume of enhancing pannus (VEP) divided by sum of the individual measurements of the joint volume. The total score ranged from 0 to 1, with 0 implying no synovitis. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Change from Baseline in synovitis was planned to be assessed by modified CARLOS.

Safety Population. Data was not collected for this outcome measure, as synovitis is not a part of modified CARLOS. Synovitis was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 26 and 27, respectively.

A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

RAMRIQ bone edema (normalised) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the Volume of bone edema divided by sum of the individual measurements of the bone volume. The total score ranged from 0 to 1, with 0 implying no bone marrow lesions. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Change from Baseline in bone edema was planned to be assessed by modified CARLOS.

Safety Population. Data was not collected for this outcome measure, as bone edema is not a part of modified CARLOS. Bone edema was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 29 and 30, respectively.

Change from Baseline in joint space narrowing was planned to be assessed by OMERACT-RAMRIS scoring system.

Safety Population. Data was not collected for this outcome measure, as joint space narrowing is not a part of OMERACT-RAMRIS scoring system. Joint space narrowing was measured by RAMRIQ scoring system and modified CARLOS and is presented in outcome measures 33 and 34, respectively.

RAMRIQ joint space narrowing was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements (in millimeter) for the joints measured. The minimum possible total score is 0 implying complete loss of the joint space. The maximum possible total score will be largest possible joint space. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

A total of 20 locations in the hand and wrist were evaluated for CARLOS joint space narrowing/cartilage loss. Individual location scores range from 0 (no cartilage loss or Joint Space Narrowing) to 4 (complete ankylosis) in increments of 0.5 based on the amount of narrowing present in a given joint. The final cartilage loss score was the sum of the individual location scores. The total score from 20 location ranged from 0 to 80, with 0 implying no cartilage loss at any location and 80 implying complete ankylosis. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Contrast agent volume transfer constant (Ktrans) relates to the exchange of contrast agent between the blood plasma and the tissue extravascular extracellular spaces and reflects blood flow and capillary permeability. Ktrans was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) tracer kinetic modeling in the most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Interstitial volume (Ve) is the fractional volume of the extravascular extracellular (EC) space per unit volume tissue within which contrast agent can accumulate. Ve was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Fractional volume of blood plasma (Vp) is the fractional volume of blood plasma per unit volume of tissue. Vp was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Initial Rate of Enhancement (IRE) is a measure of how quickly tissue enhances over 60 seconds following administration of contrast agent. IRE was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Maximum enhancement (ME) is a measure of the maximum concentration of contrast agent in the tissue over the duration of the DCE-MRI time series. ME was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

The DAS28-CRP is a composite measure of inflammation in rheumatoid arthritis calculated from the sum of tender joint count 28 (TJC28), swollen joint count (SJC28), CRP and patient global assessment of disease activity (PtGA). The formula used to calculate DAS28 score was 0.56 multiplied by square root of TJC28 plus 0.28 multiplied by square root of SJC28 plus 0.36 log of (CRP plus 1) plus 0.014 multiplied by PtGA plus 0.96. Scores of DAS28-CRP ranged from 0.96 to 9.4 with higher scores indicating greater disease burden. A DAS28-CRP score of <=2.6 suggested remission, <3.2 suggested a low level of disease activity, while a score of >5.1 suggested a high level of disease activity. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed.

DAS28-CRP 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.

Safety Population. Only those participants with data available at the specified data points were analyzed.

The ACR score was based on improvement from Baseline in tender joint counts and swollen joint counts. A participant had achieved ACR20 if he experienced >=20 percent improvement from Baseline in Tender Joint count 28 (TJC28) and Swollen Joint Count 28 (SJC28) and a >=20 percent improvement from Baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, C-reactive protein and Health Assessment Questionnaire - Disability Index (HAQ-DI). Similarly, ACR50 and ACR70 are calculated using 50 or 70 percent improvement from baseline respectively. For all visits, if any of the component scores were missing; then those scores were considered as not having met the criteria for improvement.

Safety Population

Joint volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points.

Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Enhancing volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points.

Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.