A Rheumatoid Arthritis Study in Participants

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of LY2127399 in Patients With Rheumatoid Arthritis (RA) With or Without Background Disease-Modifying Anti-rheumatic Drug (DMARD) Therapy (FLEX O)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01202760

Acronym

FLEX O

Enrollment

1004

Registered

2010-09-16

Start date

2011-01-31

Completion date

2013-07-31

Last updated

2018-04-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Brief summary

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis with or without background disease-modifying anti-rheumatic drug (DMARD) therapy. This study is comprised of 2 periods: Period 1 - 24-week blinded treatment Period 2 - 48-week post-treatment follow-up

Detailed description

In consideration of disease severity, all participants were assessed for non-response at Week 16. A total of 66 joints were examined for swelling, and a total of 66 joint were examined for tenderness. For participants who had at least 5 swollen and 5 tender joints at baseline, Week 16 non-responders (NRs) were defined as participants with \<20% improvement from baseline in both tender joint counts and swollen joint counts. For participants who did not have at least 5 swollen and 5 tender joints at baseline, Week 16 NRs were defined as participants who had at least 2 additional tender and 2 additional swollen joints from baseline. All Week 16 NRs and all participants who discontinued study treatment at any time, for any reason, were defined as NRs starting at that timepoint and going forward for all American College of Rheumatology (ACR) imputed analyses, including the Week 24 endpoint.

Interventions

DRUGLY2127399

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years * Global Assessment of Disease Activity visual analog scale (VAS) greater than or equal to 20/100 millimeters (mm) * If on one or more conventional disease-modifying anti-rheumatic Drugs (DMARDs) at randomization, must have been on a stable dose for at least 8 weeks prior to study start. * Women must not be pregnant, breastfeeding, or become pregnant during the study

Exclusion criteria

* Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks * Steroid injection or intravenous (IV) infusion in the last 6 weeks * Use of more than 10 milligrams per day (mg/day) of oral steroids in the last 6 weeks * Use of biologic DMARD concurrently or recently * History of a serious reaction to other biological DMARDs * Use of an oral calcineurin inhibitor (for example, cyclosporin or tacrolimus) in the last 8 weeks * Surgery on a joint or other major surgery less than 2 months prior to study start, or plans to have joint surgery or major surgery during the study * Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA * Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years * Received a live vaccine within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines) * Hepatitis or human immunodeficiency virus (HIV) * A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months * Symptoms of herpes zoster or herpes simplex within the last month * Active or latent tuberculosis (TB) * Current symptoms of a serious disorder or illness * Use of an investigational drug within the last month

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response	Up to 24 weeks	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>=20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)\*100. All non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.

Secondary

Measure	Time frame	Description
Mean Percent Improvement in American College of Rheumatology Percent Improvement (ACR-N)	Up to 24 weeks	ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in rheumatoid arthritis that characterizes percentage of improvement in disease activity from baseline based on ACR core set. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater percent improvement). This index was calculated as minimum of a) percentage of improvement in TJ count, b) percentage of improvement in SJ count, or c) third highest percentage of improvement of remaining 5 ACR core criteria: If \>=3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment, region, tumor necrosis factor-inadequate responder treatment history, and disease-modifying anti-rheumatic drug (DMARD) background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Tender Joint Count (68 Joint Count)	Baseline, up to 24 weeks	Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Swollen Joint Count (66 Joint Count)	Baseline, up to 24 weeks	Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Participant's Assessment of Pain (Visual Analog Scale)	Baseline, up to 24 weeks	Participant's assessment of their current arthritis pain using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Participant's Global Assessment of Disease Activity (Visual Analog Scale)	Baseline, up to 24 weeks	Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Physician's Global Assessment of Disease Activity (Visual Analog Scale)	Baseline, up to 24 weeks	Physician's assessment of the participant's current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Disease Activity Score (Based on 28 Joint Count)-C-Reactive Protein (DAS28-CRP)	Baseline, up to 24 weeks	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and participant global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP was calculated using following formula: DAS28-CRP=0.56\square root (sqrt)(TJC28)+0.28\sqrt(SJC28)+0.36\natural log(CRP+1)+0.014\participant global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI)	Baseline, up to 24 weeks	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area, which ranged from 0 (no disability) to 3 (severe disability), were averaged to calculate HAQ-DI. A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Responses	Up to 24 weeks	ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR50 Responder: had \>=50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and \>=50% improvement in at least 3/5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No) of ACR50 responders/No of Pts treated)\100. ACR70 Responder: had \>=70% improvement from baseline in both TJ and SJ counts and \>=70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response=(No of ACR70 responders/No of Pts treated)\100. All non-responders at Week 16 as well as all Pts who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.
Probability of an ACR20 Response by 24 Weeks	Baseline through 24 weeks	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.
Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR) Response	Up to 24 weeks	EULAR Responder index based on 28 joint count categorizes clinical response based on improvement since baseline in DAS28-CRP. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR28 responder is defined as either DAS28-CRP \<=5.1 and DAS28-CRP change \<-0.6; or DAS28-CRP \>5.1 and DAS28-CRP change \<-1.2. EULAR28 responder index is defined as good response: DAS28-CRP \<=3.2 and DAS28-CRP change \<-1.2; moderate response: DAS28-CRP change \<-1.2 except cases defined in good response; or DAS28-CRP \<=5.1 and DAS28-CRP change \<-0.6 and \>-1.2. EULAR Remission is defined as a DAS28-CRP score of \<2.6.
Change From Baseline to 24 Weeks in Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Survey Domain and Summary Scores	Baseline, up to 24 weeks	The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental \[MCS\] and physical health \[PCS\]). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline in C-reactive Protein (CRP) up to Week 24 Endpoint	Baseline, up to 24 weeks	CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Absolute CD3-CD20+ B-cell Counts	Baseline, up to 24 weeks	Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B-cell count is determined by calculating the average of the 2 pretreatment B-cell counts obtained once during Days -28 through -7 and on Day 0. A positive or negative change indicated an increase or decrease, respectively in B-cell count. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Change From Baseline to 24 Weeks in Serum Immunoglobulin (Ig) Levels	Baseline, up to 24 weeks	Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in immunoglobulin levels. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Population Pharmacokinetics (PK)	Baseline through 24 weeks	Population estimate of constant clearance as determined by population pharmacokinetics (PK) analysis. A 2-compartment model was used in PK modeling.
Percentage of Participants Developing Anti-LY2127399 Antibodies	Baseline through 24 weeks	LY2127399 anti-drug antibodies (ADA) were assessed at baseline, 1, 4, 16, and 24 weeks. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)\*100. Pts with treatment-emergent ADA were Pts who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or Pts who tested negative at baseline and positive post-baseline (at titer of ≥1:20).
Time to American College of Rheumatology 20% (ACR20) Response	Baseline through 24 weeks	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.

Countries

Argentina, Australia, Bulgaria, Colombia, Croatia, Hungary, India, Japan, Lithuania, Malaysia, Mexico, New Zealand, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Sri Lanka, Taiwan, Ukraine, United States

Participant flow

Participants by arm

Arm	Count
120 mg LY2127399 LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks. After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	379
90 mg LY2127399 LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	374
Placebo Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	251
Total	1,004

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	11	9	10
Overall Study	Death	2	1	0
Overall Study	Entry Criteria Not Met	0	3	1
Overall Study	Lack of Efficacy	6	8	7
Overall Study	Lost to Follow-up	0	2	1
Overall Study	Parent / Caregiver Decision	0	1	0
Overall Study	Physician Decision	0	1	0
Overall Study	Protocol Violation	7	5	2
Overall Study	Sponsor Decision	4	4	0
Overall Study	Withdrawal by Subject	17	18	14

Baseline characteristics

Characteristic	120 mg LY2127399	Total	Placebo	90 mg LY2127399
Age, Continuous	52.4 years STANDARD_DEVIATION 11.2	51.4 years STANDARD_DEVIATION 11.8	51.0 years STANDARD_DEVIATION 12	50.6 years STANDARD_DEVIATION 12.2
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants	109 Participants	24 Participants	47 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	193 Participants	511 Participants	133 Participants	185 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	148 Participants	384 Participants	94 Participants	142 Participants
Race (NIH/OMB) American Indian or Alaska Native	13 Participants	43 Participants	9 Participants	21 Participants
Race (NIH/OMB) Asian	96 Participants	248 Participants	59 Participants	93 Participants
Race (NIH/OMB) Black or African American	12 Participants	39 Participants	14 Participants	13 Participants
Race (NIH/OMB) More than one race	2 Participants	17 Participants	6 Participants	9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	2 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	4 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	254 Participants	651 Participants	162 Participants	235 Participants
Region of Enrollment Argentina	7 Participants	18 Participants	5 Participants	6 Participants
Region of Enrollment Australia	2 Participants	7 Participants	2 Participants	3 Participants
Region of Enrollment Bulgaria	13 Participants	38 Participants	12 Participants	13 Participants
Region of Enrollment Colombia	9 Participants	23 Participants	5 Participants	9 Participants
Region of Enrollment Croatia	2 Participants	6 Participants	3 Participants	1 Participants
Region of Enrollment Hungary	3 Participants	21 Participants	6 Participants	12 Participants
Region of Enrollment India	14 Participants	32 Participants	9 Participants	9 Participants
Region of Enrollment Japan	44 Participants	114 Participants	28 Participants	42 Participants
Region of Enrollment Lithuania	14 Participants	35 Participants	11 Participants	10 Participants
Region of Enrollment Malaysia	2 Participants	7 Participants	1 Participants	4 Participants
Region of Enrollment Mexico	20 Participants	60 Participants	15 Participants	25 Participants
Region of Enrollment New Zealand	6 Participants	14 Participants	6 Participants	2 Participants
Region of Enrollment Poland	27 Participants	61 Participants	12 Participants	22 Participants
Region of Enrollment Romania	0 Participants	4 Participants	3 Participants	1 Participants
Region of Enrollment Russia	14 Participants	35 Participants	8 Participants	13 Participants
Region of Enrollment Slovakia	8 Participants	13 Participants	2 Participants	3 Participants
Region of Enrollment South Africa	32 Participants	94 Participants	24 Participants	38 Participants
Region of Enrollment South Korea	7 Participants	18 Participants	5 Participants	6 Participants
Region of Enrollment Sri Lanka	4 Participants	10 Participants	2 Participants	4 Participants
Region of Enrollment Taiwan	9 Participants	23 Participants	3 Participants	11 Participants
Region of Enrollment Ukraine	16 Participants	37 Participants	6 Participants	15 Participants
Region of Enrollment United States	126 Participants	334 Participants	83 Participants	125 Participants
Sex: Female, Male Female	293 Participants	797 Participants	209 Participants	295 Participants
Sex: Female, Male Male	86 Participants	207 Participants	42 Participants	79 Participants
Swollen Joint Count (66 Count)	14.8 joint count STANDARD_DEVIATION 11.6	14.8 joint count STANDARD_DEVIATION 11.4	14.3 joint count STANDARD_DEVIATION 10.6	15.3 joint count STANDARD_DEVIATION 11.6
Tender Joint Count (68 Count)	22.8 joint count STANDARD_DEVIATION 15.5	23.2 joint count STANDARD_DEVIATION 16	22.8 joint count STANDARD_DEVIATION 15.2	23.7 joint count STANDARD_DEVIATION 17.1

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	174 / 379	154 / 371	98 / 250	23 / 81	16 / 72	9 / 56	12 / 40	17 / 45	13 / 37	5 / 7	2 / 12
serious Total, serious adverse events	14 / 379	8 / 371	7 / 250	5 / 81	0 / 72	0 / 56	0 / 40	4 / 45	3 / 37	1 / 7	2 / 12

Outcome results

Primary

Percentage of Participants With American College of Rheumatology 20% (ACR20) Response

ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>=20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)\*100. All non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.

Time frame: Up to 24 weeks

Population: All randomized participants with at least 5/68 tender joints and 5/66 swollen joints at baseline and with evaluable ACR20 data. If participant's CRP was missing, last postbaseline value was used. If ACR was missing after carrying forward CRP, last postbaseline ACR response was used. Data after Week 16 for Week 16 non-responders was not included.

Arm	Measure	Value (NUMBER)
120 mg LY2127399	Percentage of Participants With American College of Rheumatology 20% (ACR20) Response	34.4 percentage of participants
90 mg LY2127399	Percentage of Participants With American College of Rheumatology 20% (ACR20) Response	33.5 percentage of participants
Placebo	Percentage of Participants With American College of Rheumatology 20% (ACR20) Response	31.5 percentage of participants

Secondary

Change From Baseline in C-reactive Protein (CRP) up to Week 24 Endpoint

CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.