Mechanistic Study of GSK3196165 Plus Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT02799472
• Recruitment Status: Completed
• First Posted: June 14, 2016
• Results First Posted: November 16, 2018
• Last Update Posted: January 11, 2021
• Sponsor: GlaxoSmithKline
• Collaborator: Parexel
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid
• Interventions: Drug: GSK3196165; Drug: Placebo; Drug: MTX; Drug: Folic (or folinic) acid
• Enrollment: 39

Participant Flow

Recruitment Details	A total of 39 participants with active early/established Rheumatoid arthritis were randomized across 9 centers in 3 countries from 15 June 2016 to 30 October 2017.
Pre-assignment Details	Out of the 88 participants screened for this study, 49 participants were screen failures and 39 participants were randomized and received treatment in the study.

Arm/Group Title	Placebo	GSK3196165 180 mg
Arm/Group Description	Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Period Title: Overall Study
Started	11	28
Completed	7	23
Not Completed	4	5
Reason Not Completed
Withdrawal by Subject	2	4
Lack of Efficacy	2	0
Lost to Follow-up	0	1

Baseline Characteristics

Arm/Group Title		Placebo	GSK3196165 180 mg	Total
Arm/Group Description		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Total of all reporting groups
Overall Number of Baseline Participants		11	28	39
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants	28 participants	39 participants
		50.3 (11.57)	59.1 (9.47)	56.6 (10.73)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	28 participants	39 participants
	Female	10 90.9%	24 85.7%	34 87.2%
	Male	1 9.1%	4 14.3%	5 12.8%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	11 participants	28 participants	39 participants
Black or African American		2 18.2%	4 14.3%	6 15.4%
White		9 81.8%	24 85.7%	33 84.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
Description	Blood samples were collected for markers which may influence rheumatoid arthritis. Target engagement biomarkers included soluble GM-CSF complexed to GSK3196165. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for GM-CSF - Complex log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Analysis was performed on Intent-to-Treat (ITT) Population which consisted of all participants who were randomized to treatment and who received at least one dose of study treatment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of GM-CSF complex
GM-CSF - Complex, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.972; (35.98%)	13.799; (20.65%)
GM-CSF - Complex, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.960; (31.23%)	31.056; (17.58%)
GM-CSF - Complex, Week 4, n=8, 27	Number Analyzed	8 participants	27 participants
		0.959; (34.51%)	53.496; (18.55%)
GM-CSF - Complex, Week 6, n=7, 26	Number Analyzed	7 participants	26 participants
		0.964; (40.96%)	46.620; (22.37%)
GM-CSF - Complex, Week 8, n=7, 24	Number Analyzed	7 participants	24 participants
		0.964; (41.80%)	33.404; (22.47%)
GM-CSF - Complex, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.970; (44.95%)	22.556; (24.38%)
GM-CSF - Complex, 12-Week FU, n=8, 21	Number Analyzed	8 participants	21 participants
		0.954; (20.80%)	1.176; (12.88%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	14.201
	Confidence Interval	(2-Sided) 95%; 6.251 to 32.262
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	32.360
	Confidence Interval	(2-Sided) 95%; 15.828 to 66.156
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	55.772
	Confidence Interval	(2-Sided) 95%; 25.646 to 121.287
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	48.336
	Confidence Interval	(2-Sided) 95%; 19.341 to 120.798
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	34.635
	Confidence Interval	(2-Sided) 95%; 13.690 to 87.629
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	23.249
	Confidence Interval	(2-Sided) 95%; 8.579 to 63.005
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	GM-CSF - Complex, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.401
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.233
	Confidence Interval	(2-Sided) 95%; 0.742 to 2.048
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
Description	Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of 14-3-3 ETA Protein, S100 CBP A8 and A9. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for 14-3-3 ETA Protein (mg/L) and S100 CBP A8 and A9 log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of predictive biomarker
14-3-3 ETA Protein, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.046; (3.88%)	0.986; (2.16%)
14-3-3 ETA Protein, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.959; (12.14%)	0.986; (6.70%)
14-3-3 ETA Protein, Week 4, n=9, 26	Number Analyzed	9 participants	26 participants
		1.128; (16.59%)	0.838; (9.55%)
14-3-3 ETA Protein, Week 6, n=7, 26	Number Analyzed	7 participants	26 participants
		1.093; (15.55%)	0.833; (8.88%)
14-3-3 ETA Protein, Week 8, n=7, 23	Number Analyzed	7 participants	23 participants
		0.950; (15.19%)	0.842; (8.48%)
14-3-3 ETA Protein, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.131; (20.90%)	0.897; (11.89%)
14-3-3 ETA Protein, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		1.040; (24.06%)	0.893; (13.45%)
S100 CBP A8 and A9, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.940; (15.20%)	0.939; (8.92%)
S100 CBP A8 and A9, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.871; (15.28%)	0.823; (8.65%)
S100 CBP A8 and A9, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.874; (19.20%)	0.889; (11.26%)
S100 CBP A8 and A9, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		0.828; (21.92%)	0.812; (11.81%)
S100 CBP A8 and A9, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.804; (21.04%)	0.857; (11.46%)
S100 CBP A8 and A9, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.694; (21.61%)	0.879; (12.05%)
S100 CBP A8 and A9, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.582; (20.60%)	1.018; (11.83%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.193
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.943
	Confidence Interval	(2-Sided) 95%; 0.861 to 1.032
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.842
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.028
	Confidence Interval	(2-Sided) 95%; 0.776 to 1.362
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.127
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.743
	Confidence Interval	(2-Sided) 95%; 0.505 to 1.093
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.137
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.762
	Confidence Interval	(2-Sided) 95%; 0.531 to 1.095
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.488
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.886
	Confidence Interval	(2-Sided) 95%; 0.623 to 1.259
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.338
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.793
	Confidence Interval	(2-Sided) 95%; 0.488 to 1.290
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	14-3-3 ETA Protein, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.582
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.859
	Confidence Interval	(2-Sided) 95%; 0.491 to 1.502
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.996
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.999
	Confidence Interval	(2-Sided) 95%; 0.699 to 1.427
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.745
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.944
	Confidence Interval	(2-Sided) 95%; 0.662 to 1.346
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.939
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.017
	Confidence Interval	(2-Sided) 95%; 0.649 to 1.593
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.937
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.981
	Confidence Interval	(2-Sided) 95%; 0.595 to 1.617
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.787
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.067
	Confidence Interval	(2-Sided) 95%; 0.659 to 1.727
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.342
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.267
	Confidence Interval	(2-Sided) 95%; 0.769 to 2.086
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	S100 CBP A8 and A9, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.748
	Confidence Interval	(2-Sided) 95%; 1.076 to 2.838
	Estimation Comments	[Not Specified]

3. Primary Outcome

Title	Change From Baseline in Predictive Biomarkers: Amyloid A
Description	Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Amyloid A. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Amyloid A log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
Time Frame	Baseline and Week 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of predictive biomarker
Amyloid A, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.845; (49.31%)	0.653; (25.45%)
Amyloid A, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.529; (35.12%)	0.623; (19.68%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Amyloid A, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.632
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.774
	Confidence Interval	(2-Sided) 95%; 0.261 to 2.290
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Amyloid A, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.685
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.176
	Confidence Interval	(2-Sided) 95%; 0.519 to 2.663
	Estimation Comments	[Not Specified]

4. Primary Outcome

Title	Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Description	Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chemokine (C-C Motif) Ligand 17 (CL17), Chemokine (C-X-C Motif) Ligand 13 (CL13), Interleukin 6, Macrophage-Derived Chemokine (MDC). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for CL17, CL13, Interleukin 6, MDC log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
Time Frame	Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of predictive biomarker
CL17, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.117; (18.81%)	0.773; (10.94%)
CL17, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.912; (24.37%)	0.651; (13.60%)
CL17, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		1.117; (21.91%)	0.679; (12.51%)
CL17, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.032; (24.38%)	0.779; (12.48%)
CL17, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		1.211; (20.63%)	0.675; (11.21%)
CL17, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.711; (24.96%)	0.890; (13.90%)
CL17, 12-Week FU, n=7, 20	Number Analyzed	7 participants	20 participants
		1.434; (23.26%)	1.357; (13.59%)
CL13, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.198; (15.63%)	0.915; (8.87%)
CL13, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.090; (13.98%)	1.095; (7.78%)
CL13, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.947; (15.58%)	1.170; (8.90%)
CL13, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		0.839; (17.20%)	1.038; (8.91%)
CL13, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.913; (23.70%)	1.021; (12.38%)
CL13, Week 12, n=7,24	Number Analyzed	7 participants	24 participants
		0.924; (31.17%)	1.077; (16.31%)
CL13, 12-Week FU, n=7,21	Number Analyzed	7 participants	21 participants
		0.774; (27.82%)	1.224; (15.04%)
Interleukin 6, Week 1, n=9, 26	Number Analyzed	9 participants	26 participants
		1.179; (27.92%)	1.064; (16.38%)
Interleukin 6, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.153; (29.33%)	0.830; (16.63%)
Interleukin 6, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.986; (26.22%)	0.811; (15.10%)
Interleukin 6, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.136; (24.95%)	0.748; (13.51%)
Interleukin 6, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		1.275; (23.65%)	0.872; (13.35%)
Interleukin 6, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.770; (21.89%)	0.939; (12.35%)
Interleukin 6, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.817; (33.13%)	1.308; (18.63%)
MDC, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.987; (5.02%)	0.914; (2.89%)
MDC, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.925; (7.33%)	0.911; (4.15%)
MDC, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.936; (8.13%)	0.895; (4.67%)
MDC, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		0.984; (8.38%)	0.994; (4.48%)
MDC, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		1.049; (9.36%)	0.899; (5.09%)
MDC, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.245; (9.51%)	1.058; (5.23%)
MDC, 12-Week FU, n=7, 20	Number Analyzed	7 participants	20 participants
		1.303; (12.66%)	1.321; (7.53%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.097
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.692
	Confidence Interval	(2-Sided) 95%; 0.445 to 1.074
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.229
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.713
	Confidence Interval	(2-Sided) 95%; 0.407 to 1.249
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.055
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.608
	Confidence Interval	(2-Sided) 95%; 0.365 to 1.012
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.307
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.755
	Confidence Interval	(2-Sided) 95%; 0.435 to 1.309
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.557
	Confidence Interval	(2-Sided) 95%; 0.348 to 0.894
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.520
	Confidence Interval	(2-Sided) 95%; 0.294 to 0.922
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL17, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.839
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.548 to 1.636
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.142
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.764
	Confidence Interval	(2-Sided) 95%; 0.530 to 1.100
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.976
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.005
	Confidence Interval	(2-Sided) 95%; 0.726 to 1.390
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.244
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.236
	Confidence Interval	(2-Sided) 95%; 0.859 to 1.778
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.278
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.237
	Confidence Interval	(2-Sided) 95%; 0.836 to 1.830
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.677
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.118
	Confidence Interval	(2-Sided) 95%; 0.651 to 1.920
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.661
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.165
	Confidence Interval	(2-Sided) 95%; 0.573 to 2.369
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CL13, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.154
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.581
	Confidence Interval	(2-Sided) 95%; 0.832 to 3.007
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.751
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.903
	Confidence Interval	(2-Sided) 95%; 0.471 to 1.729
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.330
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.720
	Confidence Interval	(2-Sided) 95%; 0.367 to 1.413
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.519
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.822
	Confidence Interval	(2-Sided) 95%; 0.447 to 1.512
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.147
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.659
	Confidence Interval	(2-Sided) 95%; 0.372 to 1.167
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.166
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.684
	Confidence Interval	(2-Sided) 95%; 0.396 to 1.180
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.432
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.221
	Confidence Interval	(2-Sided) 95%; 0.734 to 2.031
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Interleukin 6, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.216
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.602
	Confidence Interval	(2-Sided) 95%; 0.750 to 3.423
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.195
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.926
	Confidence Interval	(2-Sided) 95%; 0.823 to 1.042
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.851
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.984
	Confidence Interval	(2-Sided) 95%; 0.829 to 1.168
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.637
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.956
	Confidence Interval	(2-Sided) 95%; 0.790 to 1.158
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.915
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.010
	Confidence Interval	(2-Sided) 95%; 0.833 to 1.225
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.157
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.857
	Confidence Interval	(2-Sided) 95%; 0.690 to 1.064
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.142
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.849
	Confidence Interval	(2-Sided) 95%; 0.681 to 1.059
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MDC, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.929
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.013
	Confidence Interval	(2-Sided) 95%; 0.745 to 1.378
	Estimation Comments	[Not Specified]

5. Primary Outcome

Title	Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Description	Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chitinase 3 Like 1 and MMP-3. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Chitinase 3 Like 1 and MMP-3 log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of predictive biomarker
Chitinase 3 Like 1, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.033; (13.97%)	0.917; (8.13%)
Chitinase 3 Like 1, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.013; (15.05%)	0.966; (8.55%)
Chitinase 3 Like 1, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.961; (17.14%)	1.088; (9.96%)
Chitinase 3 Like 1, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		0.897; (17.08%)	1.031; (8.80%)
Chitinase 3 Like 1, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.851; (18.24%)	0.947; (9.70%)
Chitinase 3 Like 1, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.066; (21.53%)	1.071; (11.64%)
Chitinase 3 Like 1, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.735; (16.87%)	1.019; (9.75%)
MMP 3, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.076; (6.72%)	0.984; (3.88%)
MMP-3, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.067; (7.26%)	1.024; (4.09%)
MMP-3, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		1.112; (8.30%)	1.016; (4.73%)
MMP-3, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.005; (26.26%)	0.804; (13.44%)
MMP-3, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.939; (15.43%)	1.088; (8.21%)
MMP-3, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.000; (13.57%)	0.951; (7.35%)
MMP-3, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.803; (16.05%)	0.984; (9.00%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.463
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.887
	Confidence Interval	(2-Sided) 95%; 0.640 to 1.231
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.782
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.953
	Confidence Interval	(2-Sided) 95%; 0.672 to 1.352
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.533
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.132
	Confidence Interval	(2-Sided) 95%; 0.759 to 1.690
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.473
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.149
	Confidence Interval	(2-Sided) 95%; 0.779 to 1.694
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.608
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.112
	Confidence Interval	(2-Sided) 95%; 0.733 to 1.687
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.985
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.005
	Confidence Interval	(2-Sided) 95%; 0.613 to 1.645
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Chitinase 3 Like 1, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.102
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.386
	Confidence Interval	(2-Sided) 95%; 0.934 to 2.057
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.259
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.915
	Confidence Interval	(2-Sided) 95%; 0.781 to 1.071
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.621
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.959
	Confidence Interval	(2-Sided) 95%; 0.809 to 1.137
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.354
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.914
	Confidence Interval	(2-Sided) 95%; 0.752 to 1.110
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.448
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.800
	Confidence Interval	(2-Sided) 95%; 0.443 to 1.444
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.402
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.160
	Confidence Interval	(2-Sided) 95%; 0.813 to 1.653
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.745
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.951
	Confidence Interval	(2-Sided) 95%; 0.695 to 1.301
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-3, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.279
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.226
	Confidence Interval	(2-Sided) 95%; 0.837 to 1.796
	Estimation Comments	[Not Specified]

6. Primary Outcome

Title	Change From Baseline in Cartilage Biomarkers
Description	Blood samples were collected and analyzed for markers that may be predictive of rheumatoid arthritis disease activity. Cartilage biomarkers included analysis of ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin (CMDV), MMP-Degraded C Reactive Protein (CRP), MMP-Degraded Type I Collagen (MD1C), MMP-Degraded Type II Collagen (MD2C), MMP-Degraded Type III Collagen (MD3C). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin, MMP-Degraded CRP, MMP-Degraded Type I Collagen, MMP-Degraded Type II Collagen and MMP-Degraded Type III Collagen log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of cartilage biomarker
ARGS Neo-Epitope, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.979; (16.10%)	1.075; (9.67%)
ARGS Neo-Epitope, Week 2, n=8, 25	Number Analyzed	8 participants	25 participants
		0.790; (17.38%)	1.249; (9.87%)
ARGS Neo-Epitope, Week 4, n=8, 26	Number Analyzed	8 participants	26 participants
		0.904; (17.02%)	1.104; (10.05%)
ARGS Neo-Epitope, Week 6, n=6, 26	Number Analyzed	6 participants	26 participants
		0.894; (14.28%)	1.164; (7.82%)
ARGS Neo-Epitope, Week 8, n=7, 24	Number Analyzed	7 participants	24 participants
		0.854; (26.42%)	1.238; (14.20%)
ARGS Neo-Epitope, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.913; (13.97%)	1.156; (7.78%)
ARGS Neo-Epitope, 12-Week FU, n=8, 21	Number Analyzed	8 participants	21 participants
		1.129; (17.44%)	1.124; (9.86%)
CMDV, Week 1,n=9,27	Number Analyzed	9 participants	27 participants
		0.981; (24.12%)	0.876; (13.80%)
CMDV,Week 2,n=8,26	Number Analyzed	8 participants	26 participants
		0.820; (28.46%)	0.714; (15.89%)
CMDV, Week 4,n=9,27	Number Analyzed	9 participants	27 participants
		0.715; (27.30%)	0.801; (15.52%)
CMDV, Week 6,n=7,27	Number Analyzed	7 participants	27 participants
		1.099; (30.47%)	0.726; (15.94%)
CMDV, Week 8,n=7,25	Number Analyzed	7 participants	25 participants
		0.929; (24.72%)	0.759; (13.39%)
CMDV, Week12,n=7,24	Number Analyzed	7 participants	24 participants
		1.123; (29.34%)	0.917; (16.00%)
CMDV, 12-Week FU,n=7,21	Number Analyzed	7 participants	21 participants
		0.936; (28.05%)	0.769; (15.81%)
MMP-Degraded CRP, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.971; (6.83%)	1.021; (3.99%)
MMP-Degraded CRP, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.970; (5.55%)	1.000; (3.07%)
MMP-Degraded CRP, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.992; (6.01%)	1.004; (3.49%)
MMP-Degraded CRP, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.122; (6.55%)	1.099; (3.50%)
MMP-Degraded CRP, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.977; (7.37%)	1.087; (4.05%)
MMP-Degraded CRP, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.006; (7.13%)	1.108; (3.95%)
MMP-Degraded CRP, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		1.075; (8.01%)	1.129; (4.48%)
MD1C, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.079; (9.60%)	0.858; (5.63%)
MD1C, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.028; (11.98%)	0.907; (6.63%)
MD1C, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		1.142; (14.57%)	0.896; (8.35%)
MD1C, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.392; (12.64%)	0.889; (6.98%)
MD1C, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		1.131; (13.05%)	0.904; (7.23%)
MD1C, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.148; (13.74%)	1.023; (7.81%)
MD1C, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		1.095; (14.21%)	0.952; (8.31%)
MD2C, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		1.059; (11.83%)	1.038; (6.88%)
MD2C, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		1.046; (11.27%)	1.015; (6.28%)
MD2C, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		1.035; (10.18%)	1.003; (5.86%)
MD2C, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.158; (12.07%)	1.064; (6.30%)
MD2C, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		1.091; (11.42%)	1.023; (6.12%)
MD2C, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		1.174; (10.73%)	1.072; (5.87%)
MD2C, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		1.338; (13.10%)	1.041; (7.50%)
MD3C, Week 1, n=9, 27	Number Analyzed	9 participants	27 participants
		0.950; (6.44%)	0.959; (3.74%)
MD3C, Week 2, n=8, 26	Number Analyzed	8 participants	26 participants
		0.920; (6.82%)	0.954; (3.91%)
MD3C, Week 4, n=9, 27	Number Analyzed	9 participants	27 participants
		0.940; (8.06%)	0.886; (4.68%)
MD3C, Week 6, n=7, 27	Number Analyzed	7 participants	27 participants
		1.013; (8.09%)	0.894; (4.34%)
MD3C, Week 8, n=7, 25	Number Analyzed	7 participants	25 participants
		0.918; (9.04%)	0.881; (4.84%)
MD3C, Week 12, n=7, 24	Number Analyzed	7 participants	24 participants
		0.929; (9.28%)	0.910; (5.08%)
MD3C, 12-Week FU, n=7, 21	Number Analyzed	7 participants	21 participants
		0.847; (9.75%)	0.910; (5.46%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.621
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.098
	Confidence Interval	(2-Sided) 95%; 0.750 to 1.606
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.031
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.581
	Confidence Interval	(2-Sided) 95%; 1.046 to 2.388
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.317
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.222
	Confidence Interval	(2-Sided) 95%; 0.817 to 1.827
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.113
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.302
	Confidence Interval	(2-Sided) 95%; 0.936 to 1.810
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.217
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.450
	Confidence Interval	(2-Sided) 95%; 0.795 to 2.645
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.147
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.266
	Confidence Interval	(2-Sided) 95%; 0.916 to 1.750
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	ARGS Neo-Epitope, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.985
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.996
	Confidence Interval	(2-Sided) 95%; 0.662 to 1.499
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.681
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.892
	Confidence Interval	(2-Sided) 95%; 0.511 to 1.560
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.668
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.870
	Confidence Interval	(2-Sided) 95%; 0.454 to 1.669
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.717
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.120
	Confidence Interval	(2-Sided) 95%; 0.597 to 2.101
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.227
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.661
	Confidence Interval	(2-Sided) 95%; 0.333 to 1.310
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.471
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.817
	Confidence Interval	(2-Sided) 95%; 0.464 to 1.437
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.541
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.816
	Confidence Interval	(2-Sided) 95%; 0.417 to 1.597
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CMDV, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.544
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.822
	Confidence Interval	(2-Sided) 95%; 0.422 to 1.602
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.537
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.051
	Confidence Interval	(2-Sided) 95%; 0.895 to 1.233
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.635
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.031
	Confidence Interval	(2-Sided) 95%; 0.906 to 1.173
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.866
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.012
	Confidence Interval	(2-Sided) 95%; 0.879 to 1.165
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.780
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.979
	Confidence Interval	(2-Sided) 95%; 0.842 to 1.139
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.212
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.113
	Confidence Interval	(2-Sided) 95%; 0.938 to 1.320
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.242
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.102
	Confidence Interval	(2-Sided) 95%; 0.934 to 1.300
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MMP-Degraded CRP, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.597
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.050
	Confidence Interval	(2-Sided) 95%; 0.870 to 1.267
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.047
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.795
	Confidence Interval	(2-Sided) 95%; 0.634 to 0.997
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.367
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.883
	Confidence Interval	(2-Sided) 95%; 0.668 to 1.165
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.155
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.784
	Confidence Interval	(2-Sided) 95%; 0.558 to 1.102
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.638
	Confidence Interval	(2-Sided) 95%; 0.477 to 0.855
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.140
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.799
	Confidence Interval	(2-Sided) 95%; 0.591 to 1.080
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.470
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.891
	Confidence Interval	(2-Sided) 95%; 0.647 to 1.228
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD1C, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.401
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.869
	Confidence Interval	(2-Sided) 95%; 0.621 to 1.217
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.887
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.981
	Confidence Interval	(2-Sided) 95%; 0.742 to 1.296
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.814
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.970
	Confidence Interval	(2-Sided) 95%; 0.744 to 1.263
	Estimation Comments	[Not Specified]

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.794
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.969
	Confidence Interval	(2-Sided) 95%; 0.762 to 1.233
	Estimation Comments	[Not Specified]

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.539
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.919
	Confidence Interval	(2-Sided) 95%; 0.696 to 1.213
	Estimation Comments	[Not Specified]

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.623
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.937
	Confidence Interval	(2-Sided) 95%; 0.719 to 1.221
	Estimation Comments	[Not Specified]

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.467
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.913
	Confidence Interval	(2-Sided) 95%; 0.711 to 1.173
	Estimation Comments	[Not Specified]

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD2C, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.108
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.778
	Confidence Interval	(2-Sided) 95%; 0.570 to 1.061
	Estimation Comments	[Not Specified]

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.897
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.010
	Confidence Interval	(2-Sided) 95%; 0.868 to 1.175
	Estimation Comments	[Not Specified]

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 2
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.644
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.037
	Confidence Interval	(2-Sided) 95%; 0.884 to 1.218
	Estimation Comments	[Not Specified]

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.530
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.943
	Confidence Interval	(2-Sided) 95%; 0.780 to 1.139
	Estimation Comments	[Not Specified]

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 6
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.182
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.882
	Confidence Interval	(2-Sided) 95%; 0.733 to 1.063
	Estimation Comments	[Not Specified]

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 8
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.691
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.960
	Confidence Interval	(2-Sided) 10%; 0.779 to 1.182
	Estimation Comments	[Not Specified]

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.843
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.979
	Confidence Interval	(2-Sided) 95%; 0.790 to 1.214
	Estimation Comments	[Not Specified]

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	MD3C, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.524
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.075
	Confidence Interval	(2-Sided) 95%; 0.855 to 1.351
	Estimation Comments	[Not Specified]

7. Primary Outcome

Title	Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
Description	Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of Helper/Suppressor. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Helper/Suppressor log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of Helper/Suppressor cells
Helper/Suppressor, Week 1, n=8, 25	Number Analyzed	8 participants	25 participants
		1.024; (6.98%)	0.976; (4.00%)
Helper/Suppressor, Week 4, n=8, 25	Number Analyzed	8 participants	25 participants
		1.053; (7.18%)	0.998; (4.11%)
Helper/Suppressor, Week 12, n=6, 25	Number Analyzed	6 participants	25 participants
		1.040; (6.83%)	1.088; (3.49%)
Helper/Suppressor, 12-Week FU, n=6, 21	Number Analyzed	6 participants	21 participants
		1.051; (8.99%)	1.065; (4.88%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Helper/Suppressor, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.558
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.953
	Confidence Interval	(2-Sided) 95%; 0.809 to 1.123
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Helper/Suppressor, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.515
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.801 to 1.120
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Helper/Suppressor, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.565
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.046
	Confidence Interval	(2-Sided) 95%; 0.895 to 1.222
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	Helper/Suppressor, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.897
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.013
	Confidence Interval	(2-Sided) 95%; 0.822 to 1.249
	Estimation Comments	[Not Specified]

8. Primary Outcome

Title	Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
Description	Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of cluster of differentiation (CD)16+CD56+, CD19, CD3, CD3+CD4+. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Repeated measures analysis adjusted for CD16+CD56+, CD19, CD3, CD3+CD4+, CD3+CD8+ and T Cell B Cell NKL log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title		Placebo	GSK3196165 180 mg
Arm/Group Description:		Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.	Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
Overall Number of Participants Analyzed		11	28
Geometric Least Squares Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of biomarker
CD16+CD56+, Week 1, n=8, 25	Number Analyzed	8 participants	25 participants
		0.989; (11.39%)	1.025; (6.30%)
CD16+CD56+, Week 4, n=8, 25	Number Analyzed	8 participants	25 participants
		1.163; (12.97%)	0.951; (7.25%)
CD16+CD56+, Week 12, n=6, 25	Number Analyzed	6 participants	25 participants
		1.193; (15.49%)	0.911; (7.81%)
CD16+CD56+, 12-Week FU, n=6, 21	Number Analyzed	6 participants	21 participants
		1.298; (15.10%)	0.920; (7.98%)
CD19, Week 1, n=8, 25	Number Analyzed	8 participants	25 participants
		0.880; (11.05%)	0.984; (6.23%)
CD19, Week 4, n=8, 25	Number Analyzed	8 participants	25 participants
		1.090; (15.31%)	0.971; (8.60%)
CD19, Week 12, n=6, 25	Number Analyzed	6 participants	25 participants
		1.054; (12.26%)	1.003; (6.51%)
CD19, Week 22, n=6, 21	Number Analyzed	6 participants	21 participants
		0.980; (17.75%)	0.938; (9.75%)
CD3, Week 1, n=8, 25	Number Analyzed	8 participants	25 participants
		0.918; (8.73%)	0.994; (4.95%)
CD3, Week 4, n=8, 25	Number Analyzed	8 participants	25 participants
		0.997; (11.79%)	0.934; (6.66%)
CD3, Week 12, n=6, 25	Number Analyzed	6 participants	25 participants
		0.912; (9.01%)	0.992; (4.60%)
CD3, 12-Week FU, n=6, 21	Number Analyzed	6 participants	21 participants
		0.931; (9.17%)	0.989; (4.98%)
CD3+CD4+, Week 1, n=8, 25	Number Analyzed	8 participants	25 participants
		0.926; (9.56%)	0.991; (5.42%)
CD3+CD4+, Week 4, n=8, 25	Number Analyzed	8 participants	25 participants
		1.028; (12.80%)	0.933; (7.23%)
CD3+CD4+, Week 12, n=6, 25	Number Analyzed	6 participants	25 participants
		0.952; (9.69%)	1.013; (4.94%)
CD3+CD4+, 12-Week FU, n=6, 21	Number Analyzed	6 participants	21 participants
		0.970; (9.92%)	1.000; (5.37%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CD16+CD56+, Week 1
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.786
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.037
	Confidence Interval	(2-Sided) 95%; 0.794 to 1.354
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CD16+CD56+, Week 4
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.188
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.818
	Confidence Interval	(2-Sided) 95%; 0.603 to 1.109
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CD16+CD56+, Week 12
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.129
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.763
	Confidence Interval	(2-Sided) 95%; 0.536 to 1.087
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180 mg
	Comments	CD16+CD56+, 12-Week FU
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.054
	Comments	[Not Specified]
	Method	Repeated measures analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.709
	Confidence Interval	(2-Sided) 95%; 0.499 to 1.006
	Estimation Comments	[Not Specified]