Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to determine whether baricitinib 4 milligram (mg) once daily (QD) is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had inadequate response to or are intolerant to at least 1 conventional disease-modifying antirheumatic drug (cDMARD)(cDMARD-IR \[inadequate response\] participants) and who have not received a biologic disease-modifying antirheumatic drug (DMARD).
Interventions
DRUGPlacebo
Administered orally
DRUGBaricitinib
Administered orally
DRUGcDMARD
Conventional disease-modifying anti-rheumatic drug as a background therapy
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of adult-onset Rheumatoid Arthritis (RA) as defined by the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria for the Classification of RA * Have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints * Have a C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP) measurement ≥ (greater than or equal to) 1.2 times the upper limit of normal (ULN) * Have had an insufficient response or are intolerant to conventional disease-modifying antirheumatic drugs (cDMARDs) and either: * Have had regular use of a cDMARD for at least the 12 weeks prior to study entry with a continuous, nonchanging dose for at least 8 weeks prior to study entry * For participants not receiving a cDMARD at the time of entry, the investigator will document in the participant's history that the participant had failed, was unable to tolerate, or had a contraindication to treatment with a cDMARD
Exclusion criteria
* Are currently receiving corticosteroids at doses \> (greater than)10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization * Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization * Are currently receiving concomitant treatment with methotrexate (MTX), hydroxychloroquine, and sulfasalazine or combination of any 3 cDMARDs * Have ever received any biologic DMARD * Have received interferon therapy within 4 weeks prior to study entry or are anticipated to require interferon therapy during the study * Have received any parenteral corticosteroid administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study * Have had 3 or more joints injected with intraarticular corticosteroids or hyaluronic acid within 2 weeks prior to study entry or within 6 weeks prior to planned randomization * Have active fibromyalgia that, in the investigator's opinion, would make it difficult to appropriately assess RA activity for the purposes of this study * Have a diagnosis of any systemic inflammatory condition other than RA, such as, but not limited to juvenile chronic arthritis,spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, active vasculitis or gout(participants with secondary Sjogren's syndrome are not excluded.) * Have a diagnosis of Felty's syndrome * Have had any major surgery within 8 weeks of study entry or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the participant * Have experienced any of the following within 12 weeks of study entry: myocardial infarction, unstable ischemic heart disease, stroke, or have New York Heart Association stage IV heart failure * Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data * Are largely or wholly incapacitated permitting little or no self care, such as, being bedridden or confined to a wheelchair * Have an estimated glomerular filtration rate (eGFR) based on the most recent available serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of \< (less than) 40 milliliter per minute per 1.73 m\^2 (mL/min/1.73 m\^2) * Have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the ULN or the most recent available total bilirubin \>/=1.5 times the ULN * Have a history of, lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for \<5 years * Have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination) * Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection * Have had symptomatic herpes zoster infection within 12 weeks prior to study entry * Have a history of disseminated/complicated herpes zoster (eg, multidermatomal involvement, ophthalmic zoster, central nervous system involvement, postherpetic neuralgia) * Are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study * Have a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) * Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population or investigative site that, in the opinion of the investigator, pose an unacceptable risk for the participant's participation in the study * Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the participant's participation in the study (eg, Fridericia's corrected QT interval \>500 millisecond \[msec\] for men and \>520 msec for women) * Have symptomatic herpes simplex at the time of study enrollment * Have evidence of active or latent tuberculosis (TB)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | Week 12 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). ACR20 Responder is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | Baseline, Week 12 | 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 Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (participant global VAS). DAS28 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\*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. |
| Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3 | Week 12 | SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Participant's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3. |
| Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries | Week 12 | Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes into daily electronic diaries. If MJS duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. The average value across the 7 days preceding each visit is calculated. A decrease in duration of MJS indicated an improvement in the participant's condition. |
| Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | Week 12 | Participants rated the severity of their MJS by selecting a number from 0 to 10 that best described their overall level of MJS from the time they woke up, where 0 represents no joint stiffness and 10 represents joint stiffness as bad as you can imagine. Participants reported their severity daily in electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in severity rating indicated an improvement in the participant's condition. |
| Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | Week 12 | Participants rated their tiredness by selecting a number from 0 to 10 that best described their level of worst tiredness during the past 24 hours, where 0 represents no tiredness and 10 represents as bad as you can imagine. Participants reported their worst tiredness in daily electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in tiredness severity rating indicated an improvement in the participant's condition. |
| Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | Week 12 | Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents no pain and 10 represents pain as bad as you can imagine. Participants reported their worst joint pain in daily electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in joint pain severity rating indicated an improvement in the participant's condition. |
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12, Week 24 | ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. ACR50 Responder is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders. |
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12, Week 24 | ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. ACR70 Responder is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders. |
| Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score | Baseline, Week 24 | • The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Baseline, Week 12 | 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 the HAQ-DI score, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. |
| Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Baseline, Week 12 | DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), Erythrocyte Sedimentation Rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-ESR=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.70\*natural log(ESR)+0.014\*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. |
| Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 12 | The ACR/EULAR definitions of RA remission includes a Boolean-based definition. The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Baseline, Week 12; Baseline Week 24 | The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (Not at all) to 4 (Very much) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. |
| Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Baseline, Week 12; Baseline, Week 24 | 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 \[PCS\]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning. |
| Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Baseline Week 12; Baseline Week 24 | European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. |
| Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Baseline Week 12; Baseline Week 24 | A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine. |
| Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Baseline, Week 12; Baseline, Week 24 | The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment. |
| Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24:predose | — |
| Population PK: Maximum Concentration at Steady State of Dosing (AUC,ss) of LY3009104 | Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24; predose | — |
| Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score | Baseline, Week 24 | The SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. The SDAI is expressed as a score on a scale with the minimum score=0 (best) to maximum score=86 (worst). A negative change from baseline indicates an improvement. |
Countries
Argentina, Australia, Belgium, Canada, Croatia, Czechia, Germany, Hungary, India, Italy, Japan, Mexico, Poland, Portugal, Puerto Rico, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Participants who did not respond (nonresponders) to study drug were eligible for rescue treatment beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered orally (PO) once daily (QD) through Week 24.
Participants continued to take background cDMARD therapy throughout study. | 228 |
| Baricitinib 2 mg Baricitinib 2 mg PO QD through week 24.
Participants continued to take background cDMARD therapy throughout study. | 229 |
| Baricitinib 4 mg Baricitinib 4 mg PO QD through week 24.
Participants continued to take background cDMARD therapy throughout study. | 227 |
| Total | 684 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Rescue Period | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Rescue Period | Lack of Efficacy | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Treatment Period | Adverse Event | 7 | 10 | 12 | 0 | 0 | 0 | 0 |
| Treatment Period | Death | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Lack of Efficacy | 7 | 3 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Physician Decision | 0 | 1 | 3 | 0 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 11 | 5 | 8 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Baricitinib 2 mg | Baricitinib 4 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 12.3 | 52.2 years STANDARD_DEVIATION 12.3 | 51.8 years STANDARD_DEVIATION 12.1 | 51.4 years STANDARD_DEVIATION 12.5 |
| Duration of Rheumatoid Arthritis | 7.5 years STANDARD_DEVIATION 7.6 | 7.6 years STANDARD_DEVIATION 7.6 | 7.7 years STANDARD_DEVIATION 7.9 | 7.2 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 15 Participants | 17 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 131 Participants | 43 Participants | 43 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 509 Participants | 171 Participants | 167 Participants | 171 Participants |
| High Sensitivity C-Reactive Protein (hsCRP) | 16.7 milligram per Liter (mg/L) STANDARD_DEVIATION 19.1 | 18.2 milligram per Liter (mg/L) STANDARD_DEVIATION 21.5 | 14.2 milligram per Liter (mg/L) STANDARD_DEVIATION 14.5 | 17.7 milligram per Liter (mg/L) STANDARD_DEVIATION 20.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 2 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 180 Participants | 61 Participants | 59 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 9 Participants | 9 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 457 Participants | 156 Participants | 148 Participants | 153 Participants |
| Region of Enrollment Argentina | 64 Participants | 21 Participants | 18 Participants | 25 Participants |
| Region of Enrollment Australia | 15 Participants | 1 Participants | 6 Participants | 8 Participants |
| Region of Enrollment Belgium | 11 Participants | 4 Participants | 6 Participants | 1 Participants |
| Region of Enrollment Canada | 28 Participants | 10 Participants | 8 Participants | 10 Participants |
| Region of Enrollment Croatia | 4 Participants | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Czech Republic | 15 Participants | 5 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Germany | 9 Participants | 2 Participants | 3 Participants | 4 Participants |
| Region of Enrollment Hungary | 20 Participants | 8 Participants | 5 Participants | 7 Participants |
| Region of Enrollment India | 58 Participants | 19 Participants | 20 Participants | 19 Participants |
| Region of Enrollment Italy | 10 Participants | 3 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Japan | 21 Participants | 6 Participants | 7 Participants | 8 Participants |
| Region of Enrollment Korea, Republic of | 17 Participants | 7 Participants | 4 Participants | 6 Participants |
| Region of Enrollment Mexico | 22 Participants | 8 Participants | 11 Participants | 3 Participants |
| Region of Enrollment Poland | 51 Participants | 13 Participants | 20 Participants | 18 Participants |
| Region of Enrollment Portugal | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Romania | 6 Participants | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Russian Federation | 20 Participants | 10 Participants | 6 Participants | 4 Participants |
| Region of Enrollment Slovakia | 11 Participants | 5 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Spain | 34 Participants | 10 Participants | 10 Participants | 14 Participants |
| Region of Enrollment Taiwan | 82 Participants | 28 Participants | 28 Participants | 26 Participants |
| Region of Enrollment United Kingdom | 5 Participants | 4 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 176 Participants | 58 Participants | 60 Participants | 58 Participants |
| Sex: Female, Male Female | 560 Participants | 184 Participants | 187 Participants | 189 Participants |
| Sex: Female, Male Male | 124 Participants | 45 Participants | 40 Participants | 39 Participants |
| Swollen Joint Count of 66 Evaluable Joints | 13.4 Number of Joints STANDARD_DEVIATION 7.6 | 13.6 Number of Joints STANDARD_DEVIATION 8.7 | 13.5 Number of Joints STANDARD_DEVIATION 6.9 | 13.1 Number of Joints STANDARD_DEVIATION 7.2 |
| Tender Joint Count of 68 Evaluable Joints | 24.0 Number of Joints STANDARD_DEVIATION 14.3 | 23.5 Number of Joints STANDARD_DEVIATION 14.1 | 24.3 Number of Joints STANDARD_DEVIATION 14 | 24.3 Number of Joints STANDARD_DEVIATION 15 |
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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 105 / 228 | 108 / 229 | 127 / 227 | 21 / 91 | 2 / 17 | 0 / 19 | 4 / 22 |
| serious Total, serious adverse events | 13 / 228 | 6 / 229 | 12 / 227 | 1 / 91 | 1 / 17 | 0 / 19 | 1 / 22 |
Outcome results
Primary
Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). ACR20 Responder is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Time frame: Week 12
Population: Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using non-responder imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 39.5 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 65.9 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 61.7 percentage of participants |
p-value: 0.001Regression, Logistic
Secondary
Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR)
DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), Erythrocyte Sedimentation Rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-ESR=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.70\*natural log(ESR)+0.014\*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Time frame: Baseline, Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR) | -1.16 units on a scale | Standard Deviation 1.27 |
| Baricitinib 2 mg | Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR) | -1.89 units on a scale | Standard Deviation 1.23 |
| Baricitinib 4 mg | Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR) | -1.97 units on a scale | Standard Deviation 1.16 |
Secondary
Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores
European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state.
Time frame: Baseline Week 12; Baseline Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug , with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 12 | 0.054 units on a scale | Standard Deviation 0.155 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.051 units on a scale | Standard Deviation 0.149 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.074 units on a scale | Standard Deviation 0.23 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.075 units on a scale | Standard Deviation 0.218 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.162 units on a scale | Standard Deviation 0.254 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 12 | 0.117 units on a scale | Standard Deviation 0.151 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.167 units on a scale | Standard Deviation 0.221 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.113 units on a scale | Standard Deviation 0.172 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.185 units on a scale | Standard Deviation 0.25 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.129 units on a scale | Standard Deviation 0.173 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.159 units on a scale | Standard Deviation 0.237 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 12 | 0.109 units on a scale | Standard Deviation 0.165 |
Secondary
Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)
A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine.
Time frame: Baseline Week 12; Baseline Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug , with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 12 | 5.7 mm | Standard Deviation 23.8 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 24 | 8.4 mm | Standard Deviation 25.1 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 12 | 13.4 mm | Standard Deviation 21.8 |
| Baricitinib 2 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 24 | 13.1 mm | Standard Deviation 25.8 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 12 | 11.5 mm | Standard Deviation 25.2 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health, Week 24 | 10.4 mm | Standard Deviation 28.8 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores.
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (Not at all) to 4 (Very much) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.
Time frame: Baseline, Week 12; Baseline Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug , with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 12 | 7.6 units on a scale | Standard Deviation 10.3 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 24 | 7.8 units on a scale | Standard Deviation 11 |
| Baricitinib 2 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 12 | 8.7 units on a scale | Standard Deviation 11.1 |
| Baricitinib 2 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 24 | 9.2 units on a scale | Standard Deviation 10.7 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 12 | 8.8 units on a scale | Standard Deviation 10.6 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores. | Week 24 | 9.7 units on a scale | Standard Deviation 10.8 |
Secondary
Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score
• The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.
Time frame: Baseline, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified last observation carried forward (mLOCF) .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score | -14.29 units on a scale | Standard Deviation 16.04 |
| Baricitinib 2 mg | Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score | -20.99 units on a scale | Standard Deviation 14.48 |
| Baricitinib 4 mg | Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score | -23.18 units on a scale | Standard Deviation 13.47 |
Secondary
Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score
The SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. The SDAI is expressed as a score on a scale with the minimum score=0 (best) to maximum score=86 (worst). A negative change from baseline indicates an improvement.
Time frame: Baseline, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score | -14.55 units on a scale | Standard Deviation 16.37 |
| Baricitinib 2 mg | Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score | -21.87 units on a scale | Standard Deviation 14.99 |
| Baricitinib 4 mg | Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score | -23.78 units on a scale | Standard Deviation 13.94 |
Secondary
Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)
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 \[PCS\]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
Time frame: Baseline, Week 12; Baseline, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug , with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, MCS | 3.3 units on a scale | Standard Deviation 10.6 |
| Placebo | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, MCS | 2.7 units on a scale | Standard Deviation 11.5 |
| Placebo | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, PCS | 4.1 units on a scale | Standard Deviation 7.3 |
| Placebo | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, PCS | 4.9 units on a scale | Standard Deviation 8 |
| Baricitinib 2 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, PCS | 8.5 units on a scale | Standard Deviation 9 |
| Baricitinib 2 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, MCS | 3.6 units on a scale | Standard Deviation 10.5 |
| Baricitinib 2 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, PCS | 7.7 units on a scale | Standard Deviation 8.5 |
| Baricitinib 2 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, MCS | 3.0 units on a scale | Standard Deviation 10.4 |
| Baricitinib 4 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, PCS | 8.6 units on a scale | Standard Deviation 9 |
| Baricitinib 4 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 24, MCS | 3.3 units on a scale | Standard Deviation 11.3 |
| Baricitinib 4 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, PCS | 7.0 units on a scale | Standard Deviation 8.3 |
| Baricitinib 4 mg | Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) | Week 12, MCS | 3.3 units on a scale | Standard Deviation 11 |
Secondary
Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)
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 Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (participant global VAS). DAS28 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\*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Time frame: Baseline, Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | -1.05 units on a scale | Standard Deviation 1.23 |
| Baricitinib 2 mg | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | -1.83 units on a scale | Standard Deviation 1.22 |
| Baricitinib 4 mg | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | -1.91 units on a scale | Standard Deviation 1.21 |
Secondary
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
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 the HAQ-DI score, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time frame: Baseline, Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified baseline observation carried forward (mBOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | -0.30 units on a scale | Standard Deviation 0.45 |
| Baricitinib 2 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | -0.52 units on a scale | Standard Deviation 0.59 |
| Baricitinib 4 mg | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | -0.52 units on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment.
Time frame: Baseline, Week 12; Baseline, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Change from baseline includes participants with a baseline value and an observed value at the time point being summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | 2.6 percentage of impairment | Standard Deviation 23.5 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | -2.1 percentage of impairment | Standard Deviation 13.9 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -8 percentage of impairment | Standard Deviation 26 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -17 percentage of impairment | Standard Deviation 26 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 | -4.2 percentage of impairment | Standard Deviation 27.7 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Producivity Loss Week 24 | -15.9 percentage of impairment | Standard Deviation 26.1 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -13 percentage of impairment | Standard Deviation 25 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -18 percentage of impairment | Standard Deviation 27 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -17 percentage of impairment | Standard Deviation 25 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -19 percentage of impairment | Standard Deviation 27 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -20 percentage of impairment | Standard Deviation 23 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 | -17.6 percentage of impairment | Standard Deviation 30.4 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Producivity Loss Week 24 | -19.6 percentage of impairment | Standard Deviation 25 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | -6.3 percentage of impairment | Standard Deviation 26.5 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | -3.8 percentage of impairment | Standard Deviation 28.2 |
| Baricitinib 2 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -23 percentage of impairment | Standard Deviation 28 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -15 percentage of impairment | Standard Deviation 27 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | 4.0 percentage of impairment | Standard Deviation 27.2 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | 2.5 percentage of impairment | Standard Deviation 24.7 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -17 percentage of impairment | Standard Deviation 21 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -19 percentage of impairment | Standard Deviation 25 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Producivity Loss Week 24 | -14.3 percentage of impairment | Standard Deviation 23 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 | -9.9 percentage of impairment | Standard Deviation 23.7 |
| Baricitinib 4 mg | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -21 percentage of impairment | Standard Deviation 27 |
Secondary
Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries
Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes into daily electronic diaries. If MJS duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. The average value across the 7 days preceding each visit is calculated. A decrease in duration of MJS indicated an improvement in the participant's condition.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries | 60.0 minutes |
| Baricitinib 2 mg | Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries | 44.4 minutes |
| Baricitinib 4 mg | Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries | 34.6 minutes |
Secondary
Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries
Participants rated the severity of their MJS by selecting a number from 0 to 10 that best described their overall level of MJS from the time they woke up, where 0 represents no joint stiffness and 10 represents joint stiffness as bad as you can imagine. Participants reported their severity daily in electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in severity rating indicated an improvement in the participant's condition.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 4.2 units on a scale | Standard Deviation 2.3 |
| Baricitinib 2 mg | Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.5 units on a scale | Standard Deviation 2.5 |
| Baricitinib 4 mg | Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.4 units on a scale | Standard Deviation 2.2 |
Secondary
Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries
Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents no pain and 10 represents pain as bad as you can imagine. Participants reported their worst joint pain in daily electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in joint pain severity rating indicated an improvement in the participant's condition.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 4.7 units on a scale | Standard Deviation 2.2 |
| Baricitinib 2 mg | Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.9 units on a scale | Standard Deviation 2.5 |
| Baricitinib 4 mg | Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.8 units on a scale | Standard Deviation 2.2 |
Secondary
Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries
Participants rated their tiredness by selecting a number from 0 to 10 that best described their level of worst tiredness during the past 24 hours, where 0 represents no tiredness and 10 represents as bad as you can imagine. Participants reported their worst tiredness in daily electronic diaries. The average value across the 7 days preceding each visit is calculated. A decrease in tiredness severity rating indicated an improvement in the participant's condition.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 4.5 units on a scale | Standard Deviation 2.2 |
| Baricitinib 2 mg | Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 4.0 units on a scale | Standard Deviation 2.5 |
| Baricitinib 4 mg | Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 4.0 units on a scale | Standard Deviation 2.3 |
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. ACR50 Responder is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Time frame: Week 12, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 12.7 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 21.5 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 33.6 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 41.5 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 33.5 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 44.1 percentage of participants |
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. ACR70 Responder is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Time frame: Week 12, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 3.1 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 7.9 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 17.9 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 25.3 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 18.1 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 24.2 percentage of participants |
Secondary
Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission
The ACR/EULAR definitions of RA remission includes a Boolean-based definition. The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | 0.4 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | 7.0 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | 6.6 percentage of participants |
Secondary
Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3
SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Participant's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3.
Time frame: Week 12
Population: mITT population: all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3 | 0.9 percentage of participants |
| Baricitinib 2 mg | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3 | 9.2 percentage of participants |
| Baricitinib 4 mg | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3 | 8.8 percentage of participants |
Secondary
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Time frame: Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24:predose
Population: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 70.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.2 |
| Baricitinib 2 mg | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 138 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25.7 |
Secondary
Population PK: Maximum Concentration at Steady State of Dosing (AUC,ss) of LY3009104
Time frame: Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24; predose
Population: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Population PK: Maximum Concentration at Steady State of Dosing (AUC,ss) of LY3009104 | 637 nanograms per mL per hour (ng/mL*h) | Geometric Coefficient of Variation 44.5 |
| Baricitinib 2 mg | Population PK: Maximum Concentration at Steady State of Dosing (AUC,ss) of LY3009104 | 1210 nanograms per mL per hour (ng/mL*h) | Geometric Coefficient of Variation 47 |