Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to determine whether baricitinib 4 milligram (mg) once daily is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had an inadequate response to a tumor necrosis factor (TNF) inhibitor, despite ongoing treatment with conventional disease-modifying antirheumatic drugs (cDMARDs).
Interventions
DRUGPlacebo
Administered orally
DRUGBaricitinib
Administered orally
DRUGcDMARD
Participants will continue to take background cDMARD therapy throughout study.
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 times the upper limit of normal (ULN) * Have been treated at approved doses with at least 1 biologic tumor necrosis factor (TNF)- alpha inhibitor for at least 3 months and either: * experienced insufficient efficacy or loss of efficacy * experienced intolerance of such treatment * Have had regular use of at least 1 conventional disease-modifying antirheumatic drugs (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
Exclusion criteria
* Have received a biologic treatment for RA within 28 days of planned randomization; have received rituximab within 6 months of planned randomization * 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 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 (e.g. Fridericia's corrected QT interval \>500 millisecond \[msec\]) * 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% (ACR20) Response - Placebo Versus Baricitinib 4 mg | Week 12 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg | Baseline, Week 12 | DAS-28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), high sensitivity C-reactive protein (hsCRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-hsCRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*Patient's Global VAS+0.96. Total scores ranged from 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 - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg | Week 12 | The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity. |
| Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg | Week 12 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. |
| Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg | 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. Total scores 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 the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg | Baseline, Week 12 | DAS28 consisted of composite score of following variables: TJC28, SJC28, hsCRP (mg/mL), and Patient's Global Assessment of Disease Activity. 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. |
| Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg | Week 12 | The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity. |
| Percentage of Participants Achieving ACR20 Response | Week 24 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. |
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 and Week 24 | ACR50 Responder Index is a 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's 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 time point are deemed non-responders. |
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 and Week 24 | ACR70 Responder Index is a 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's 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 time point are deemed non-responders. |
| Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR) | Baseline, Week 12 | DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. |
| Change From Baseline in Clinical Disease Activity Index 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 HAQ-DI Score - Placebo Versus Baricitinib 4 mg | 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. |
| Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission | Week 24 | 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 Duration of Participant Reported Outcome - Morning Joint Stiffness | Baseline, Week 24 | Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on that day. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition. |
| Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) | Baseline, Week 24 | A participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no tiredness) and 10 representing (as bad as you can imagine). Participants rate their tiredness by selecting the one number that describes their worst level of tiredness during the past 24 hours. Total scores ranged from 0-10. |
| Change From Baseline in Worst Joint Pain NRS | Baseline, Week 24 | Participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no joint pain) and 10 representing (pain as bad as you can imagine). Participants rate their joint pain by selecting the one number that describes their worst level of joint pain during the past 24 hours. Total scores ranged from 0-10. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Baseline, Week 12, 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, 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. |
| Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Baseline, Week 12, Week 24 | European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The first component is 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. The second component is a self-perceived health score which is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. |
| Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Baseline, Week 12, Week 24 | The WPAI-RA participant 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. Using 6 questions, it yields four types of scores: absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment, with outcomes expressed as impairment percentages. Percentage work time missed absenteeism: Q2/(Q2+Q4)\*100, Percentage impairment while working presenteeism: Q5/10\*100; Percentage overall work impairment work productivity loss: Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))x(Q5/10)\]\*100; Percentage activity impairment activity impairment: Q6/10\*100. Higher numbers indicate greater impairment and less productivity, that is, worse outcomes. |
| Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib | Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose. | — |
| Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib | Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose. | — |
| Change From Baseline in Measures of 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, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Participants who did not adequately respond (nonresponders) to study drug were eligible for rescue treatment with baricitinib 4 mg 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 PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. | 176 |
| Baricitinib 2 mg Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. | 174 |
| Baricitinib 4 mg Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. | 177 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period | Adverse Event | 7 | 7 | 10 |
| Treatment Period | Death | 0 | 0 | 1 |
| Treatment Period | Lack of Efficacy | 16 | 4 | 4 |
| Treatment Period | Lost to Follow-up | 0 | 0 | 1 |
| Treatment Period | Physician Decision | 1 | 0 | 2 |
| Treatment Period | Protocol Violation | 1 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 7 | 6 | 1 |
Baseline characteristics
| Characteristic | Baricitinib 2 mg | Baricitinib 4 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 55.1 Years STANDARD_DEVIATION 11.1 | 55.9 Years STANDARD_DEVIATION 11.3 | 56.0 Years STANDARD_DEVIATION 10.7 | 55.7 Years STANDARD_DEVIATION 11 |
| Duration of Rheumatoid Arthritis | 13.7 Years STANDARD_DEVIATION 8 | 14.3 Years STANDARD_DEVIATION 9.4 | 14.0 Years STANDARD_DEVIATION 9.6 | 14.0 Years STANDARD_DEVIATION 9 |
| High Sensitivity C-Reactive Protein (hsCRP) | 19.87 milligrams/liter (mg/L) STANDARD_DEVIATION 22.48 | 19.76 milligrams/liter (mg/L) STANDARD_DEVIATION 24.84 | 20.64 milligrams/liter (mg/L) STANDARD_DEVIATION 25.26 | 20.09 milligrams/liter (mg/L) STANDARD_DEVIATION 24.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 12 Participants | 11 Participants | 9 Participants | 32 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 12 Participants | 11 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 7 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 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 | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 144 Participants | 144 Participants | 147 Participants | 435 Participants |
| Region of Enrollment Argentina | 5 Participants | 7 Participants | 9 Participants | 21 Participants |
| Region of Enrollment Australia | 9 Participants | 4 Participants | 8 Participants | 21 Participants |
| Region of Enrollment Austria | 3 Participants | 8 Participants | 5 Participants | 16 Participants |
| Region of Enrollment Belgium | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Canada | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Region of Enrollment Denmark | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Region of Enrollment France | 10 Participants | 7 Participants | 7 Participants | 24 Participants |
| Region of Enrollment Germany | 5 Participants | 6 Participants | 8 Participants | 19 Participants |
| Region of Enrollment Greece | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Israel | 8 Participants | 13 Participants | 9 Participants | 30 Participants |
| Region of Enrollment Italy | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Region of Enrollment Japan | 6 Participants | 8 Participants | 6 Participants | 20 Participants |
| Region of Enrollment Mexico | 12 Participants | 10 Participants | 9 Participants | 31 Participants |
| Region of Enrollment Netherlands | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Poland | 13 Participants | 9 Participants | 10 Participants | 32 Participants |
| Region of Enrollment South Korea | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Region of Enrollment Spain | 7 Participants | 10 Participants | 10 Participants | 27 Participants |
| Region of Enrollment Switzerland | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Region of Enrollment Turkey | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 74 Participants | 75 Participants | 77 Participants | 226 Participants |
| Sex: Female, Male Female | 137 Participants | 149 Participants | 145 Participants | 431 Participants |
| Sex: Female, Male Male | 37 Participants | 28 Participants | 31 Participants | 96 Participants |
| Swollen Joint Count of 66 Evaluable Joints | 18.6 Number of Joints STANDARD_DEVIATION 12.3 | 16.3 Number of Joints STANDARD_DEVIATION 8.9 | 17.2 Number of Joints STANDARD_DEVIATION 10.8 | 17.4 Number of Joints STANDARD_DEVIATION 10.8 |
| Tender Joint Count of 68 Evaluable Joints | 31.0 Number of Joints STANDARD_DEVIATION 16.3 | 28.1 Number of Joints STANDARD_DEVIATION 15.6 | 28.3 Number of Joints STANDARD_DEVIATION 16.4 | 29.1 Number of Joints STANDARD_DEVIATION 16.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 79 / 176 | 105 / 174 | 102 / 177 | 6 / 127 | 2 / 19 | 4 / 9 | 1 / 20 |
| serious Total, serious adverse events | 14 / 176 | 8 / 174 | 19 / 177 | 2 / 127 | 1 / 19 | 1 / 9 | 0 / 20 |
Outcome results
Primary
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. 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% (ACR20) Response - Placebo Versus Baricitinib 4 mg | 27.3 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg | 55.4 Percentage of Participants |
p-value: 0.001Regression, Logistic
Secondary
Change From Baseline in Clinical Disease Activity Index 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 includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 Clinical Disease Activity Index Score | -12.19 Units on a Scale | Standard Deviation 16.96 |
| Baricitinib 4 mg | Change From Baseline in Clinical Disease Activity Index Score | -17.17 Units on a Scale | Standard Deviation 16.96 |
| Baricitinib 4 mg | Change From Baseline in Clinical Disease Activity Index Score | -20.30 Units on a Scale | Standard Deviation 16.29 |
p-value: 0.001ANCOVA
p-value: 0.009ANCOVA
Secondary
Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)
DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time frame: Baseline, Week 12
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 DAS28 - Erythrocyte Sedimentation Rate (ESR) | -0.92 Units on a Scale | Standard Deviation 1.21 |
| Baricitinib 4 mg | Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR) | -1.52 Units on a Scale | Standard Deviation 1.37 |
| Baricitinib 4 mg | Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR) | -1.80 Units on a Scale | Standard Deviation 1.44 |
p-value: 0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness
Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on that day. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
Time frame: Baseline, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness | -8.0 Minutes |
| Baricitinib 4 mg | Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness | -25.5 Minutes |
| Baricitinib 4 mg | Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness | -27.0 Minutes |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.004Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The first component is 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. The second component is a self-perceived health score which is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine.
Time frame: Baseline, Week 12, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 Scores | Index Score (US Algorithm) Wk 12 (N=168,168,173) | 0.035 Units on a Scale | Standard Deviation 0.167 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (US Algorithm) Wk 24 (N=167,168,173) | 0.042 Units on a Scale | Standard Deviation 0.166 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 12 (N=168,168,173) | 0.052 Units on a Scale | Standard Deviation 0.25 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 24 (N=167,168,173) | 0.064 Units on a Scale | Standard Deviation 0.245 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 12 (N=168,168,173) | 4.1 Units on a Scale | Standard Deviation 29 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 24 (N=167,168,173) | 3.8 Units on a Scale | Standard Deviation 27.8 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 24 (N=167,168,173) | 11.4 Units on a Scale | Standard Deviation 26.5 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (US Algorithm) Wk 12 (N=168,168,173) | 0.080 Units on a Scale | Standard Deviation 0.152 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 24 (N=167,168,173) | 0.122 Units on a Scale | Standard Deviation 0.25 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 12 (N=168,168,173) | 14.1 Units on a Scale | Standard Deviation 24.2 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (US Algorithm) Wk 24 (N=167,168,173) | 0.082 Units on a Scale | Standard Deviation 0.17 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 12 (N=168,168,173) | 0.116 Units on a Scale | Standard Deviation 0.224 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (US Algorithm) Wk 24 (N=167,168,173) | 0.128 Units on a Scale | Standard Deviation 0.157 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 12 (N=168,168,173) | 0.191 Units on a Scale | Standard Deviation 0.224 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 24 (N=167,168,173) | 13.3 Units on a Scale | Standard Deviation 29 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (UK Algorithm) Wk 24 (N=167,168,173) | 0.192 Units on a Scale | Standard Deviation 0.237 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Index Score (US Algorithm) Wk 12 (N=168,168,173) | 0.128 Units on a Scale | Standard Deviation 0.148 |
| Baricitinib 4 mg | Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores | Self-Perceived Health Wk 12 (N=168,168,173) | 10.3 Units on a Scale | Standard Deviation 27.3 |
Comparison: Week 12, US Algorithmp-value: 0.001ANCOVA
Comparison: Week 12, US Algorithmp-value: 0.001ANCOVA
Comparison: Week 24, US Algorithmp-value: 0.001ANCOVA
Comparison: Week 24, US Algorithmp-value: 0.003ANCOVA
Comparison: Week 12, UK Algorithmp-value: 0.001ANCOVA
Comparison: Week 12, UK Algorithmp-value: 0.001ANCOVA
Comparison: Week 24, UK Algorithmp-value: 0.001ANCOVA
Comparison: Week 24, UK Algorithmp-value: 0.002ANCOVA
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale 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, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 Scale Scores | Week 24 | 6.6 Units on a Scale | Standard Deviation 10.7 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Week 12 | 5.9 Units on a Scale | Standard Deviation 10.5 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Week 12 | 8.8 Units on a Scale | Standard Deviation 10 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Week 24 | 8.8 Units on a Scale | Standard Deviation 10.4 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Week 12 | 8.5 Units on a Scale | Standard Deviation 9.9 |
| Baricitinib 4 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores | Week 24 | 9.7 Units on a Scale | Standard Deviation 10.7 |
Comparison: Week 12p-value: 0.005ANCOVA
Comparison: Week 12p-value: 0.004ANCOVA
Comparison: Week 24p-value: 0.002ANCOVA
Comparison: Week 24p-value: 0.026ANCOVA
Secondary
Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg
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. Total scores 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 includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 HAQ-DI Score - Placebo Versus Baricitinib 2 mg | -0.20 Units on a Scale | Standard Deviation 0.5 |
| Baricitinib 4 mg | Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg | -0.38 Units on a Scale | Standard Deviation 0.51 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg
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 includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 HAQ-DI Score - Placebo Versus Baricitinib 4 mg | -0.20 Units on a Scale | Standard Deviation 0.5 |
| Baricitinib 4 mg | Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg | -0.42 Units on a Scale | Standard Deviation 0.49 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Measures of 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 includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 SDAI Score | -12.07 Units on a Scale | Standard Deviation 17.5 |
| Baricitinib 4 mg | Change From Baseline in Measures of SDAI Score | -17.80 Units on a Scale | Standard Deviation 17.5 |
| Baricitinib 4 mg | Change From Baseline in Measures of SDAI Score | -21.26 Units on a Scale | Standard Deviation 17.01 |
p-value: 0.001ANCOVA
p-value: 0.003ANCOVA
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.
Time frame: Baseline, Week 12, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
| 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 PCS | 3.3 Units on a Scale | Standard Deviation 8 |
| 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 | 1.6 Units on a Scale | Standard Deviation 10.7 |
| 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 | 2.4 Units on a Scale | Standard Deviation 8.2 |
| 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 | 2.5 Units on a Scale | Standard Deviation 10.8 |
| 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 | 6.3 Units on a Scale | Standard Deviation 8.8 |
| 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 | 3.2 Units on a Scale | Standard Deviation 11.5 |
| 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 | 6.4 Units on a Scale | Standard Deviation 8.9 |
| 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 12 MCS | 3.4 Units on a Scale | Standard Deviation 9.7 |
| 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 | 7.0 Units on a Scale | Standard Deviation 9.3 |
| 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 | 2.4 Units on a Scale | Standard Deviation 10 |
| 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 10.6 |
| 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 | 6.4 Units on a Scale | Standard Deviation 8.8 |
Comparison: MCS Week 12p-value: 0.448ANCOVA
Comparison: MCS Week 12p-value: 0.058ANCOVA
Comparison: MCS Week 24p-value: 0.446ANCOVA
Comparison: MCS Week 24p-value: 0.401ANCOVA
Comparison: PCS Week 12p-value: 0.001ANCOVA
Comparison: PCS Week 12p-value: 0.001ANCOVA
Comparison: PCS Week 24p-value: 0.001ANCOVA
Comparison: PCS Week 24p-value: 0.001ANCOVA
Secondary
Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg
DAS28 consisted of composite score of following variables: TJC28, SJC28, hsCRP (mg/mL), and Patient's Global Assessment of Disease Activity. 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time frame: Baseline, Week 12
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg | -0.85 Units on a Scale | Standard Deviation 1.19 |
| Baricitinib 4 mg | Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg | -1.53 Units on a Scale | Standard Deviation 1.34 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg
DAS-28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), high sensitivity C-reactive protein (hsCRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-hsCRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*Patient's Global VAS+0.96. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time frame: Baseline, Week 12
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg | -0.85 Units on a Scale | Standard Deviation 1.19 |
| Baricitinib 4 mg | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg | -1.81 Units on a Scale | Standard Deviation 1.43 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Worst Joint Pain NRS
Participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no joint pain) and 10 representing (pain as bad as you can imagine). Participants rate their joint pain by selecting the one number that describes their worst level of joint pain during the past 24 hours. Total scores ranged from 0-10.
Time frame: Baseline, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 Worst Joint Pain NRS | -1.2 Units on a Scale | Standard Deviation 2.4 |
| Baricitinib 4 mg | Change From Baseline in Worst Joint Pain NRS | -2.1 Units on a Scale | Standard Deviation 2.5 |
| Baricitinib 4 mg | Change From Baseline in Worst Joint Pain NRS | -2.5 Units on a Scale | Standard Deviation 2.7 |
p-value: 0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)
A participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no tiredness) and 10 representing (as bad as you can imagine). Participants rate their tiredness by selecting the one number that describes their worst level of tiredness during the past 24 hours. Total scores ranged from 0-10.
Time frame: Baseline, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 Worst Tiredness Numeric Rating Scale (NRS) | -1.1 Units on a Scale | Standard Deviation 2.3 |
| Baricitinib 4 mg | Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) | -1.8 Units on a Scale | Standard Deviation 2.7 |
| Baricitinib 4 mg | Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) | -2.0 Units on a Scale | Standard Deviation 2.6 |
p-value: 0.001ANCOVA
p-value: 0.018ANCOVA
Secondary
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
The WPAI-RA participant 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. Using 6 questions, it yields four types of scores: absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment, with outcomes expressed as impairment percentages. Percentage work time missed absenteeism: Q2/(Q2+Q4)\*100, Percentage impairment while working presenteeism: Q5/10\*100; Percentage overall work impairment work productivity loss: Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))x(Q5/10)\]\*100; Percentage activity impairment activity impairment: Q6/10\*100. Higher numbers indicate greater impairment and less productivity, that is, worse outcomes.
Time frame: Baseline, Week 12, Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | 3.2 Percentage of Impairment | Standard Deviation 23.8 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | 0.9 Percentage of Impairment | Standard Deviation 12.4 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -4.1 Percentage of Impairment | Standard Deviation 26.4 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -7.1 Percentage of Impairment | Standard Deviation 30.5 |
| Placebo | Percentage 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 27.8 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 | -6.0 Percentage of Impairment | Standard Deviation 33.4 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -10.4 Percentage of Impairment | Standard Deviation 22.8 |
| Placebo | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -15.7 Percentage of Impairment | Standard Deviation 25.5 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -12.0 Percentage of Impairment | Standard Deviation 24 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -16.0 Percentage of Impairment | Standard Deviation 25.5 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -11.4 Percentage of Impairment | Standard Deviation 24.9 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 | -13.7 Percentage of Impairment | Standard Deviation 26.7 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 | -13.2 Percentage of Impairment | Standard Deviation 27.6 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | -6.7 Percentage of Impairment | Standard Deviation 26.6 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | -1.9 Percentage of Impairment | Standard Deviation 31.4 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -20.8 Percentage of Impairment | Standard Deviation 23.7 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 | -10.5 Percentage of Impairment | Standard Deviation 24 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 | -2.3 Percentage of Impairment | Standard Deviation 29.5 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 | -6.5 Percentage of Impairment | Standard Deviation 22.1 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 | -15.6 Percentage of Impairment | Standard Deviation 25.4 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 | -18.1 Percentage of Impairment | Standard Deviation 24.8 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 | -14.8 Percentage of Impairment | Standard Deviation 32.4 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 | -12.3 Percentage of Impairment | Standard Deviation 24.8 |
| Baricitinib 4 mg | Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 | -25.8 Percentage of Impairment | Standard Deviation 25.2 |
Comparison: Absenteeism Week 12p-value: 0.362ANCOVA
Comparison: Absenteeism Week 12p-value: 0.17ANCOVA
Comparison: Absenteeism Week 24p-value: 0.753ANCOVA
Comparison: Absenteeism Week 24p-value: 0.715ANCOVA
Comparison: Presenteeism Week 12p-value: 0.077ANCOVA
Comparison: Presenteeism Week 12p-value: 0.058ANCOVA
Comparison: Presenteeism Week 24p-value: 0.232ANCOVA
Comparison: Presenteeism Week 24p-value: 0.534ANCOVA
Comparison: Work Productivity Loss Week 12p-value: 0.079ANCOVA
Comparison: Work Productivity Loss Week 12p-value: 0.07ANCOVA
Comparison: Work Productivity Loss Week 24p-value: 0.327ANCOVA
Comparison: Work Productivity Loss Week 24p-value: 0.479ANCOVA
Comparison: Activity Impairment Week 12p-value: 0.001ANCOVA
Comparison: Activity Impairment Week 12p-value: 0.005ANCOVA
Comparison: Activity Impairment Week 24p-value: 0.001ANCOVA
Comparison: Activity Impairment Week 24p-value: 0.03ANCOVA
Secondary
Percentage of Participants Achieving ACR20 Response
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time frame: Week 24
Population: Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. 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 ACR20 Response | 27.3 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR20 Response | 44.8 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR20 Response | 46.3 Percentage of Participants |
p-value: 0.001Regression, Logistic
p-value: 0.001Regression, Logistic
Secondary
Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time frame: Week 12
Population: Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. 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 ACR20 Response - Placebo Versus Baricitinib 2 mg | 27.3 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg | 48.9 Percentage of Participants |
p-value: 0.001Regression, Logistic
Secondary
Percentage of Participants Achieving 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 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 ACR/EULAR Remission - Boolean Remission | 1.1 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission | 4.0 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission | 6.8 Percentage of Participants |
p-value: 0.012Regression, Logistic
p-value: 0.104Regression, Logistic
Secondary
Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg
The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity.
Time frame: Week 12
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized or assigned per protocol. 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 ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg | 1.7 Percent of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg | 2.3 Percent of Participants |
p-value: 0.723Regression, Logistic
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 Responder Index is a 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's 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 time point are deemed non-responders.
Time frame: Week 12 and Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 | 8.0 Percentage of Participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 13.1 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 20.1 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 23.0 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 28.2 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 24 | 29.4 Percentage of Participants |
Comparison: Week 12p-value: 0.001Regression, Logistic
Comparison: Week 12p-value: 0.002Regression, Logistic
Comparison: Week 24p-value: 0.001Regression, Logistic
Comparison: Week 24p-value: 0.015Regression, Logistic
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 Responder Index is a 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's 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 time point are deemed non-responders.
Time frame: Week 12 and Week 24
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 | 2.3 Percentage of Participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 3.4 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 12.6 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 13.2 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 11.3 Percentage of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 16.9 Percentage of Participants |
Comparison: Week 12p-value: 0.002Regression, Logistic
Comparison: Week 12p-value: 0.001Regression, Logistic
Comparison: Week 24p-value: 0.001Regression, Logistic
Comparison: Week 24p-value: 0.001Regression, Logistic
Secondary
Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg
The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity.
Time frame: Week 12
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized or assigned per protocol. 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 - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg | 1.7 Percent of Participants |
| Baricitinib 4 mg | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg | 5.1 Percent of Participants |
p-value: 0.14Regression, Logistic
Secondary
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib
Time frame: Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
Population: All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data. Participants who initially received 2 mg with renal impairment were randomized to 4mg (N=11). Participants starting on 4mg (N=177) and participants rescued to 4mg (N=33) are included in the PK baricitinib 4 mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib | 65.6 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 21.4 |
| Baricitinib 4 mg | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib | 130 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 19.3 |
Secondary
Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
Time frame: Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
Population: All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib | 615 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 43.1 |
| Baricitinib 4 mg | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib | 1140 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 38.7 |