Rheumatoid Arthritis
Conditions
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 in participants with an inadequate response to one or more tumor necrosis factor-alpha (TNF-α) inhibitors. This study is comprised of 2 periods: Period 1: 24-week blinded treatment Period 2: 48-week post-treatment follow-up
Interventions
DRUGLY2127399
Administered Subcutaneously (SC)
DRUGPlacebo Q4W
Administered SC
DRUGPlacebo Q2W
Administered SC
Sponsors
Eli Lilly and Company
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
No
Inclusion criteria
* Diagnosis of RA of more than 6 months and less than 15 years * At least 8 tender and swollen joints * An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR) * Positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody * Previously treated with biologic TNF-α inhibitor therapy (infliximab, certolizumab, golimumab, etanercept, adalimumab) and stopped treatment due to insufficient efficacy or intolerance * Regular use of at least 1 conventional disease-modifying anti-rheumatic drug (DMARD), with a stable dose for at least 8 weeks prior to study start * Woman must not be pregnant, breastfeeding, or become pregnant during the study
Exclusion criteria
* Use of unstable doses of non-steroidal anti-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/day (mg/day) of oral steroids in the last 6 weeks * 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 ago, 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 received 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 | Baseline through Week 24 | ACR Responder Index: composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: a ≥20% improvement from baseline in both 68 tender joint counts (TJC) and 66 swollen joint counts (SJC) and a ≥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 NR at Week 16, as well as all participants who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology Percent Improvement (ACR-N) | Baseline through Week 24 | ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJC, b) % change in SJC, or c) the median % change 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. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline Disease Activity Score based on 28 joint counts -CRP (DAS28-CRP) as a covariate. |
| Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count) | Baseline, Week 24 | 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 was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count) | Baseline, Week 24 | 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 and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)] | Baseline, Week 24 | Participant's assessment of their current arthritis pain using 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 and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS) | Baseline, Week 24 | Participant's assessment of their current arthritis disease activity using VAS ranged from 0 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 and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS) | Baseline, Week 24 | Physician's assessment of the participant's current arthritis disease activity using VAS ranged from 0 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 and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline, Week 24 | 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 were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) | Baseline, Week 24 | 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), CRP (milligrams per liter), and participant's global assessment of disease activity using VAS (participant global VAS). 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 from 1.0 to 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 and region as fixed factors and baseline as a covariate. |
| Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Baseline through Week 24 | EULAR Responder index categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP=0.56\*sqrt(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response = ( number of participants with specific response) / (number of participants analyzed in the group) \* 100. |
| Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | Baseline through Week 24 | ACR Responder Index: composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had a ≥50% improvement from baseline in both 68 TJC and 66 SJC and a ≥50% improvement in at least 3 of 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 a ≥70% improvement from baseline in both TJC and SJC and a ≥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 NR at Week 16, as well as all Pts who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint. |
| Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Baseline, Week 24 | The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, the first item is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Baseline, Week 24 | The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24 hours and pain based on the pain right now, with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in the past 24 hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life \[each item scored from 0 (does not interfere) to 10 (completely interferes)\]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes) | Baseline, Week 24 | The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Time to ACR20 Response | Baseline through Week 24 | — |
| Change From Baseline to Week 24 in Absolute B Cell Counts | Baseline, Week 24 | 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 the average of the values on or prior to the date of first injection of study treatment, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | Baseline, Week 24 | Immunoglobulin (Ig), 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 in serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. |
| Population Pharmacokinetics (PK): Constant Clearance | Baseline through Week 24 | Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum. |
| Percentage of Participants Developing Anti-LY2127399 Antibodies | Baseline through Week 24 | Participants with treatment-emergent anti-drug antibody (ADA) were participants who had any sample from baseline up to and through Week 52 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Percentage of participants with ADA = (number of participants with treatment-emergent ADA) / (number of participants assessed) \* 100. |
| Change From Baseline to Week 24 in CRP | Baseline, Week 24 | 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 and region as fixed factors and baseline as a covariate. |
| Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Baseline, Week 24 | 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, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. If \< 50% of the questions within a domain were answered, the raw score were not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher score indicating better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate. |
Countries
Argentina, Australia, Brazil, Colombia, France, Germany, Greece, Italy, Japan, Malaysia, Mexico, New Zealand, Poland, Russia, South Africa, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Study had a treatment period (Weeks 0-24) and a post-treatment follow-up period (24-48 weeks in length). All participants were assessed for nonresponse at Week 16 with non-responders (NR) defined as participants with \<20% improvement from baseline in both tender and swollen joint counts.
Participants by arm
| Arm | Count |
|---|---|
| 120 mg LY2127399 A loading dose of 240 mg (2 injections of 120 mg) of LY2127399 followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 24 weeks. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 24-week treatment period. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.
At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period. | 153 |
| 90 mg LY2127399 A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 24 weeks.
At Week 16, both responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period. | 148 |
| Placebo A loading dose of 2 injections of placebo followed by maintenance dosing of 1 injection of placebo administered SC Q2W for 24 weeks. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period.
At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period. | 155 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 5 |
| Overall Study | Entry Criteria Not Met | 2 | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 4 | 9 |
| Overall Study | Lost to Follow-up | 1 | 2 | 2 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 11 | 6 | 10 |
| Overall Study | Sponsor Decision | 19 | 20 | 23 |
| Overall Study | Withdrawal by Subject | 13 | 6 | 5 |
Baseline characteristics
| Characteristic | 120 mg LY2127399 | 90 mg LY2127399 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 11.6 | 51.3 years STANDARD_DEVIATION 11.7 | 54.0 years STANDARD_DEVIATION 11.1 | 53.2 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants | 36 Participants | 33 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 95 Participants | 101 Participants | 289 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants | 17 Participants | 21 Participants | 59 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 9 Participants | 6 Participants | 23 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 9 Participants | 13 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 16 Participants | 18 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 119 Participants | 108 Participants | 112 Participants | 339 Participants |
| Region of Enrollment Argentina | 5 Participants | 4 Participants | 4 Participants | 13 Participants |
| Region of Enrollment Australia | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Brazil | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Region of Enrollment Colombia | 10 Participants | 7 Participants | 12 Participants | 29 Participants |
| Region of Enrollment France | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Germany | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Region of Enrollment Greece | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Japan | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Region of Enrollment Malaysia | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Mexico | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Region of Enrollment New Zealand | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Poland | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Region of Enrollment Russia | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Region of Enrollment South Africa | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment South Korea | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Spain | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Taiwan | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 89 Participants | 90 Participants | 89 Participants | 268 Participants |
| Sex: Female, Male Female | 124 Participants | 126 Participants | 131 Participants | 381 Participants |
| Sex: Female, Male Male | 29 Participants | 22 Participants | 24 Participants | 75 Participants |
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 | 71 / 153 | 51 / 147 | 61 / 154 | 10 / 23 | 11 / 33 | 16 / 37 | 6 / 43 | 11 / 36 | 14 / 44 | 0 / 3 | 1 / 7 |
| serious Total, serious adverse events | 7 / 153 | 6 / 147 | 6 / 154 | 1 / 23 | 2 / 33 | 1 / 37 | 1 / 43 | 1 / 36 | 3 / 44 | 0 / 3 | 0 / 7 |
Outcome results
Primary
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
ACR Responder Index: composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: a ≥20% improvement from baseline in both 68 tender joint counts (TJC) and 66 swollen joint counts (SJC) and a ≥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 NR at Week 16, as well as all participants who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint.
Time frame: Baseline through Week 24
Population: All randomized participants with evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 120 mg LY2127399 | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | 17.6 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | 24.3 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | 20.0 percentage of participants |
Secondary
American College of Rheumatology Percent Improvement (ACR-N)
ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJC, b) % change in SJC, or c) the median % change 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. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline Disease Activity Score based on 28 joint counts -CRP (DAS28-CRP) as a covariate.
Time frame: Baseline through Week 24
Population: All randomized participants with evaluable ACR-N data. Modified Baseline Observation Carried Forward (mBOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | American College of Rheumatology Percent Improvement (ACR-N) | -9.03 percentage of improvement | Standard Error 4 |
| 90 mg LY2127399 | American College of Rheumatology Percent Improvement (ACR-N) | -8.03 percentage of improvement | Standard Error 4.11 |
| Placebo | American College of Rheumatology Percent Improvement (ACR-N) | -12.72 percentage of improvement | Standard Error 4 |
Secondary
Change From Baseline to Week 24 in Absolute B Cell Counts
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 the average of the values on or prior to the date of first injection of study treatment, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable CD3-CD20+ B cell counts. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Absolute B Cell Counts | -55.3 cells/microliter (cells/µL) | Standard Error 9.9 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Absolute B Cell Counts | -65.8 cells/microliter (cells/µL) | Standard Error 10.1 |
| Placebo | Change From Baseline to Week 24 in Absolute B Cell Counts | 3.2 cells/microliter (cells/µL) | Standard Error 9.8 |
Secondary
Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores
The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, the first item is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable BFI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Now | -0.68 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Usual | -0.65 units on a scale | Standard Error 0.11 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Worst | -0.75 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | General Activity | -0.55 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Mood | -0.54 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Walking Ability | -0.53 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Normal Work | -0.60 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Relations with Other People | -0.41 units on a scale | Standard Error 0.12 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Enjoyment of Life | -0.53 units on a scale | Standard Error 0.13 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue Impact Subscale | -0.52 units on a scale | Standard Error 0.11 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Enjoyment of Life | -0.55 units on a scale | Standard Error 0.13 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Now | -0.55 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Walking Ability | -0.38 units on a scale | Standard Error 0.13 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Mood | -0.35 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Usual | -0.58 units on a scale | Standard Error 0.11 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue Impact Subscale | -0.43 units on a scale | Standard Error 0.11 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Relations with Other People | -0.43 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Worst | -0.65 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Normal Work | -0.46 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | General Activity | -0.50 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Relations with Other People | -0.29 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | General Activity | -0.52 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Mood | -0.35 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Walking Ability | -0.36 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Enjoyment of Life | -0.41 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Normal Work | -0.42 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Now | -0.60 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue Impact Subscale | -0.39 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Usual | -0.56 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores | Fatigue - Worst | -0.72 units on a scale | Standard Error 0.12 |
Secondary
Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores
The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24 hours and pain based on the pain right now, with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in the past 24 hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life \[each item scored from 0 (does not interfere) to 10 (completely interferes)\]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable BPI-SF scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Worst | -0.9 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Least | -0.5 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Average | -0.7 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Now | -0.8 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | General Activity | -0.7 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Mood | -0.6 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Walking Ability | -0.8 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Normal Work | -0.7 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Relations with Other People | -0.3 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Sleep | -0.7 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Enjoyment of Life | -0.7 units on a scale | Standard Error 0.2 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain Interference Score | -0.6 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain Interference Score | -0.3 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Worst | -0.8 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Walking Ability | -0.4 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Relations with Other People | -0.2 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Least | -0.5 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Mood | -0.2 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Enjoyment of Life | -0.4 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Average | -0.7 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Normal Work | -0.4 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | General Activity | -0.4 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Now | -0.5 units on a scale | Standard Error 0.2 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Sleep | -0.3 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Now | -0.3 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | General Activity | -0.3 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Sleep | -0.4 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Mood | -0.0 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Walking Ability | -0.4 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Normal Work | -0.2 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Enjoyment of Life | -0.4 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Worst | -0.4 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Least | -0.1 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Relations with Other People | -0.1 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain - Average | -0.3 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores | Pain Interference Score | -0.3 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline to Week 24 in CRP
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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in CRP | 2.91 milligrams/liter (mg/L) | Standard Error 1.83 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in CRP | 0.95 milligrams/liter (mg/L) | Standard Error 1.87 |
| Placebo | Change From Baseline to Week 24 in CRP | 2.93 milligrams/liter (mg/L) | Standard Error 1.81 |
Secondary
Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)
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), CRP (milligrams per liter), and participant's global assessment of disease activity using VAS (participant global VAS). 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 from 1.0 to 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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable DAS28-CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) | -0.76 units on a scale | Standard Error 0.12 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) | -0.79 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) | -0.72 units on a scale | Standard Error 0.12 |
Secondary
Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)
The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable morning stiffness data; mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes) | -20.6 minutes | Standard Error 11.5 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes) | -1.0 minutes | Standard Error 11.7 |
| Placebo | Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes) | -18.0 minutes | Standard Error 11.9 |
Secondary
Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)
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 were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable HAQ-DI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.13 units on a scale | Standard Error 0.05 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.09 units on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.08 units on a scale | Standard Error 0.05 |
Secondary
Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores
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, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. If \< 50% of the questions within a domain were answered, the raw score were not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher score indicating better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable SF-36 domain and summary scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Physical Functioning | 1.81 units on a scale | Standard Error 0.78 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Bodily Pain | 2.36 units on a scale | Standard Error 0.75 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Physical Problems | 1.92 units on a scale | Standard Error 0.72 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Emotional Problems | 1.07 units on a scale | Standard Error 0.97 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | General Health Perception | 1.90 units on a scale | Standard Error 0.64 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Mental Health | 0.83 units on a scale | Standard Error 0.85 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Social Function | 2.51 units on a scale | Standard Error 0.87 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Vitality | 2.71 units on a scale | Standard Error 0.77 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | PCS | 2.30 units on a scale | Standard Error 0.71 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | MCS | 1.22 units on a scale | Standard Error 0.87 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | PCS | 1.83 units on a scale | Standard Error 0.74 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Physical Functioning | 1.78 units on a scale | Standard Error 0.82 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Mental Health | 1.57 units on a scale | Standard Error 0.88 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | General Health Perception | 0.91 units on a scale | Standard Error 0.67 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Bodily Pain | 2.95 units on a scale | Standard Error 0.78 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | MCS | 1.86 units on a scale | Standard Error 0.9 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Vitality | 2.40 units on a scale | Standard Error 0.8 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Physical Problems | 2.08 units on a scale | Standard Error 0.75 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Social Function | 1.68 units on a scale | Standard Error 0.91 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Emotional Problems | 2.55 units on a scale | Standard Error 1.01 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Vitality | 2.05 units on a scale | Standard Error 0.76 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Emotional Problems | 1.19 units on a scale | Standard Error 0.96 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | General Health Perception | 1.88 units on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Mental Health | 0.98 units on a scale | Standard Error 0.84 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | PCS | 1.21 units on a scale | Standard Error 0.71 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Social Function | 1.32 units on a scale | Standard Error 0.86 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Physical Functioning | 1.00 units on a scale | Standard Error 0.77 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | MCS | 1.38 units on a scale | Standard Error 0.86 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Bodily Pain | 1.97 units on a scale | Standard Error 0.74 |
| Placebo | Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores | Role Limitations due to Physical Problems | 0.35 units on a scale | Standard Error 0.72 |
Secondary
Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)]
Participant's assessment of their current arthritis pain using 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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable participant's assessment of pain data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)] | -9.89 mm | Standard Error 2.1 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)] | -9.15 mm | Standard Error 2.15 |
| Placebo | Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)] | -5.76 mm | Standard Error 2.1 |
Secondary
Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS)
Participant's assessment of their current arthritis disease activity using VAS ranged from 0 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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable participant's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS) | -11.29 mm | Standard Error 2.14 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS) | -8.72 mm | Standard Error 2.19 |
| Placebo | Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS) | -7.12 mm | Standard Error 2.13 |
Secondary
Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS)
Physician's assessment of the participant's current arthritis disease activity using VAS ranged from 0 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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable physician's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS) | -15.90 mm | Standard Error 2.16 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS) | -16.38 mm | Standard Error 2.23 |
| Placebo | Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS) | -13.17 mm | Standard Error 2.13 |
Secondary
Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels
Immunoglobulin (Ig), 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 in serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable serum Ig data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgG | -0.955 grams/liter (g/L) | Standard Error 0.161 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgA | -0.330 grams/liter (g/L) | Standard Error 0.049 |
| 120 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgM | -0.273 grams/liter (g/L) | Standard Error 0.043 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgG | -0.978 grams/liter (g/L) | Standard Error 0.163 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgA | -0.324 grams/liter (g/L) | Standard Error 0.05 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgM | -0.239 grams/liter (g/L) | Standard Error 0.044 |
| Placebo | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgA | 0.003 grams/liter (g/L) | Standard Error 0.049 |
| Placebo | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgM | -0.019 grams/liter (g/L) | Standard Error 0.042 |
| Placebo | Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels | IgG | 0.058 grams/liter (g/L) | Standard Error 0.158 |
Secondary
Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count)
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 and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable swollen joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count) | -6.02 joint counts | Standard Error 0.98 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count) | -5.64 joint counts | Standard Error 1 |
| Placebo | Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count) | -5.41 joint counts | Standard Error 0.98 |
Secondary
Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)
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 was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time frame: Baseline, Week 24
Population: All randomized participants with evaluable tender joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count) | -6.37 joint counts | Standard Error 1.4 |
| 90 mg LY2127399 | Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count) | -6.08 joint counts | Standard Error 1.42 |
| Placebo | Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count) | -6.56 joint counts | Standard Error 1.38 |
Secondary
Percentage of Participants Developing Anti-LY2127399 Antibodies
Participants with treatment-emergent anti-drug antibody (ADA) were participants who had any sample from baseline up to and through Week 52 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Percentage of participants with ADA = (number of participants with treatment-emergent ADA) / (number of participants assessed) \* 100.
Time frame: Baseline through Week 24
Population: All randomized participants who received at least 1 dose of study drug with an evaluable baseline ADA result and a post-baseline ADA result. Participants missing an evaluable baseline result with all negative post-baseline results were included. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 120 mg LY2127399 | Percentage of Participants Developing Anti-LY2127399 Antibodies | 3.9 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants Developing Anti-LY2127399 Antibodies | 4.8 percentage of participants |
| Placebo | Percentage of Participants Developing Anti-LY2127399 Antibodies | 3.9 percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
ACR Responder Index: composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had a ≥50% improvement from baseline in both 68 TJC and 66 SJC and a ≥50% improvement in at least 3 of 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 a ≥70% improvement from baseline in both TJC and SJC and a ≥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 NR at Week 16, as well as all Pts who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint.
Time frame: Baseline through Week 24
Population: All randomized participants with evaluable ACR50 or ACR70 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 120 mg LY2127399 | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 | 7.2 percentage of participants |
| 120 mg LY2127399 | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 | 2.6 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 | 5.4 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 | 2.0 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 | 3.9 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 | 0.6 percentage of participants |
Secondary
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response
EULAR Responder index categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP=0.56\*sqrt(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response = ( number of participants with specific response) / (number of participants analyzed in the group) \* 100.
Time frame: Baseline through Week 24
Population: All randomized participants with evaluable EULAR response data. Modified Last Observation Carried Forward (mLOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 120 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Moderate | 36.2 percentage of participants |
| 120 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Good | 11.8 percentage of participants |
| 120 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | No response | 52.0 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Moderate | 36.3 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Good | 9.6 percentage of participants |
| 90 mg LY2127399 | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | No response | 54.1 percentage of participants |
| Placebo | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Good | 8.6 percentage of participants |
| Placebo | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | No response | 55.3 percentage of participants |
| Placebo | Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response | Moderate | 36.2 percentage of participants |
Secondary
Population Pharmacokinetics (PK): Constant Clearance
Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.
Time frame: Baseline through Week 24
Population: All randomized participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 | Population Pharmacokinetics (PK): Constant Clearance | 4.16 milliliters/hour (mL/h) | Standard Error 3.58 |
Secondary
Time to ACR20 Response
Time frame: Baseline through Week 24
Population: Zero participants analyzed. Time to ACR20 data not collected for analysis.