Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to determine whether baricitinib is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had an inadequate response to methotrexate (MTX) treatment.
Interventions
DRUGAdalimumab
Administered SC
DRUGBaricitinib
Administered orally
DRUGMethotrexate
Administered orally
Adalimumab placebo administered SC.
Baricitinib placebo administered orally.
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 ≥6 milligram per Liter (mg/L) * Have had regular use of methotrexate (MTX) for at least the 12 weeks prior to study entry at a dose that is considered acceptable to adequately assess clinical response. * Have at least 1 joint erosion in hand, wrist, or foot joints based on radiographic interpretation by the central reader and be rheumatoid factor or anticyclic citrullinated peptide (anti-CCP) antibody positive; or have at least 3 joint erosions in hand, wrist, or foot joints based on radiographic interpretation by the central reader regardless of rheumatoid factor or anti-CCP antibody status
Exclusion criteria
* Are currently receiving corticosteroids at doses \>10 mg of prednisone per day (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 MTX, hydroxychloroquine, and sulfasalazine or combination of any 3 conventional disease-modifying antirheumatic drugs (cDMARDs) * Are currently receiving or have received cDMARDs (eg, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine (up to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 4 weeks prior to study entry * Have received leflunomide in the 12 weeks prior to study entry * Have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry * Have ever received any biologic disease-modifying antirheumatic drugs (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 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 any condition or contraindication for adalimumab that would preclude the participant from participating in this protocol * Have active fibromyalgia that 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 Sjögren's syndrome are not excluded) * Have a diagnosis of Felty's syndrome * Have had any major surgery within 8 weeks prior to 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 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 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, or 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 * 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 discontinued study or drug or were rescued before analysis timepoint were deemed non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Modified Total Sharp Score (mTSS) | Baseline, Week 24 | X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS. This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448. |
| 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 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 American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | Week 12, Week 24, Week 52 | ACR50 and ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR50 and ACR70 Responder is a participant who has at least 50% or 70% improvement, respectively, 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 discontinued study or drug or were rescued before analysis time point were deemed non-responders. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline, Week 12, Week 24, Week 52 | 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. |
| Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries | Week 12 | Participants recorded the duration of their morning joint stiffness (MJS) in hours and minutes into electronic diaries daily. If morning joint stiffness 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 was calculated. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition. |
| Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 12, Week 24, Week 52 | 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 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 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 morning joint stiffness by selecting a number from 0 to 10 that best described their overall level of morning joint stiffness 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 was calculated. |
| 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 worst tiredness during the last 24 hours, where 0 represents no tiredness and 10 represents as bad as you can imagine. Participants reported their worst tiredness in electronic diaries. The average value across the 7 days preceding each visit is calculated. |
| Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 12, Week 24, Week 52 | 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) Scale Scores | Baseline, Week 12, Week 24, Week 52 | 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, Week 52 | 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, Week 24, Week 52 | 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, Week 24, Week 52 | 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, Week 24, Week 52 | 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. |
| Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Baseline, Week 24, Week 52 | X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion). |
| Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib | Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 12; Week 24; Week 32: Pre-dose | — |
| Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib | Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 12; Week 24; Week 32: Pre-dose | — |
| Mean Worst Joint Pain 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 was calculated. |
Countries
Argentina, Belgium, Canada, China, Croatia, Czechia, France, Germany, Greece, Hungary, Japan, Latvia, Lithuania, Mexico, Poland, Portugal, Puerto Rico, Romania, Russia, Slovakia, Slovenia, South Africa, South Korea, Spain, Switzerland, 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 Week16. Participants not rescued at Week 16 may be rescued at the discretion of the investigator anytime thereafter. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered orally once daily through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50.
At Week 24, participants were given baricitinib 4 milligram (mg) orally once daily through Week 52.
Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52.
Participants continued to take background methotrexate (MTX) therapy throughout study. | 488 |
| Baricitinib Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50.
Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52.
Participants continued to take background MTX therapy throughout study. | 487 |
| Adalimumab Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52.
Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52.
Participants continued to take background MTX) therapy throughout study. | 330 |
| Total | 1,305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Rescue Period | Adverse Event | 0 | 15 | 0 |
| Rescue Period | Death | 0 | 1 | 0 |
| Rescue Period | Lack of Efficacy | 0 | 7 | 0 |
| Rescue Period | Withdrawal by Subject | 0 | 8 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Adverse Event | 15 | 18 | 7 |
| Treatment Period Part A (Weeks 0 to 24) | Death | 0 | 2 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Entry Criteria Not Met | 0 | 1 | 1 |
| Treatment Period Part A (Weeks 0 to 24) | Lack of Efficacy | 15 | 1 | 3 |
| Treatment Period Part A (Weeks 0 to 24) | Lost to Follow-up | 0 | 1 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Physician Decision | 1 | 0 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Randomized But Not Treated | 1 | 1 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Sponsor Decision | 4 | 0 | 0 |
| Treatment Period Part A (Weeks 0 to 24) | Withdrawal by Subject | 15 | 5 | 12 |
| Treatment Period Part B (Weeks 24 to 52) | Adverse Event | 10 | 16 | 5 |
| Treatment Period Part B (Weeks 24 to 52) | Death | 1 | 0 | 1 |
| Treatment Period Part B (Weeks 24 to 52) | Lack of Efficacy | 0 | 0 | 1 |
| Treatment Period Part B (Weeks 24 to 52) | Lost to Follow-up | 0 | 0 | 1 |
| Treatment Period Part B (Weeks 24 to 52) | Physician Decision | 0 | 1 | 0 |
| Treatment Period Part B (Weeks 24 to 52) | Sponsor Decision | 1 | 2 | 0 |
| Treatment Period Part B (Weeks 24 to 52) | Withdrawal by Subject | 4 | 3 | 7 |
Baseline characteristics
| Characteristic | Total | Placebo | Baricitinib | Adalimumab |
|---|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 12.1 | 53.4 years STANDARD_DEVIATION 11.8 | 53.5 years STANDARD_DEVIATION 12.2 | 52.9 years STANDARD_DEVIATION 12.3 |
| Duration of Rheumatoid Arthritis | 10.1 years STANDARD_DEVIATION 8.7 | 10.4 years STANDARD_DEVIATION 8.7 | 10.3 years STANDARD_DEVIATION 8.8 | 9.6 years STANDARD_DEVIATION 8.5 |
| High Sensitivity C-Reactive Protein (hsCRP) | 21.14 milligrams per liter (mg/L) STANDARD_DEVIATION 21.67 | 19.66 milligrams per liter (mg/L) STANDARD_DEVIATION 20.97 | 22.20 milligrams per liter (mg/L) STANDARD_DEVIATION 22.85 | 21.78 milligrams per liter (mg/L) STANDARD_DEVIATION 20.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 63 Participants | 26 Participants | 19 Participants | 18 Participants |
| Race (NIH/OMB) Asian | 392 Participants | 148 Participants | 143 Participants | 101 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 21 Participants | 7 Participants | 11 Participants | 3 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 818 Participants | 302 Participants | 312 Participants | 204 Participants |
| Region of Enrollment Argentina | 255 Participants | 91 Participants | 107 Participants | 57 Participants |
| Region of Enrollment Belgium | 8 Participants | 2 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Canada | 11 Participants | 5 Participants | 4 Participants | 2 Participants |
| Region of Enrollment China | 54 Participants | 21 Participants | 22 Participants | 11 Participants |
| Region of Enrollment Croatia | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Czechia | 36 Participants | 16 Participants | 10 Participants | 10 Participants |
| Region of Enrollment France | 23 Participants | 8 Participants | 8 Participants | 7 Participants |
| Region of Enrollment Germany | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Greece | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Hungary | 37 Participants | 18 Participants | 11 Participants | 8 Participants |
| Region of Enrollment Japan | 249 Participants | 93 Participants | 93 Participants | 63 Participants |
| Region of Enrollment Latvia | 9 Participants | 2 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Lithuania | 26 Participants | 4 Participants | 12 Participants | 10 Participants |
| Region of Enrollment Mexico | 125 Participants | 50 Participants | 36 Participants | 39 Participants |
| Region of Enrollment Poland | 80 Participants | 26 Participants | 35 Participants | 19 Participants |
| Region of Enrollment Portugal | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Romania | 16 Participants | 8 Participants | 6 Participants | 2 Participants |
| Region of Enrollment Russia | 78 Participants | 27 Participants | 28 Participants | 23 Participants |
| Region of Enrollment Slovakia | 20 Participants | 8 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Slovenia | 5 Participants | 4 Participants | 1 Participants | 0 Participants |
| Region of Enrollment South Africa | 56 Participants | 24 Participants | 21 Participants | 11 Participants |
| Region of Enrollment South Korea | 57 Participants | 21 Participants | 21 Participants | 15 Participants |
| Region of Enrollment Spain | 31 Participants | 15 Participants | 11 Participants | 5 Participants |
| Region of Enrollment Taiwan | 18 Participants | 6 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United Kingdom | 8 Participants | 2 Participants | 6 Participants | 0 Participants |
| Region of Enrollment United States | 94 Participants | 34 Participants | 36 Participants | 24 Participants |
| Sex: Female, Male Female | 1008 Participants | 382 Participants | 375 Participants | 251 Participants |
| Sex: Female, Male Male | 297 Participants | 106 Participants | 112 Participants | 79 Participants |
| Swollen Joint Count of 66 Evaluable Joints | 15.3 Number of Joints STANDARD_DEVIATION 8.9 | 15.5 Number of Joints STANDARD_DEVIATION 9.4 | 15.0 Number of Joints STANDARD_DEVIATION 8.2 | 15.4 Number of Joints STANDARD_DEVIATION 9.1 |
| Tender Joint Count of 68 Evaluable Joints | 23.4 Number of Joints STANDARD_DEVIATION 13.3 | 23.3 Number of Joints STANDARD_DEVIATION 13.5 | 23.4 Number of Joints STANDARD_DEVIATION 13 | 23.4 Number of Joints STANDARD_DEVIATION 13.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 177 / 488 | 196 / 487 | 132 / 330 | 58 / 306 | 70 / 424 | 38 / 267 | 46 / 227 | 3 / 33 | 0 / 76 | 3 / 20 |
| serious Total, serious adverse events | 26 / 488 | 26 / 487 | 7 / 330 | 12 / 306 | 16 / 424 | 9 / 267 | 17 / 227 | 2 / 33 | 0 / 76 | 0 / 20 |
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 discontinued study or drug or were rescued before analysis timepoint were deemed non-responders.
Time frame: Week 12
Population: Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using nonresponder imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 40.2 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 69.6 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) | 61.2 percentage of participants |
p-value: 0.001Regression, Logistic
Secondary
Change From Baseline in 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 12, Week 24, Week 52
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 | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 24 | -14.21 units on a scale | Standard Deviation 15.13 |
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 12 | -13.53 units on a scale | Standard Deviation 13.88 |
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 52 | NA units on a scale | — |
| Baricitinib | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 24 | -25.04 units on a scale | Standard Deviation 13.61 |
| Baricitinib | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 12 | -23.00 units on a scale | Standard Deviation 12.66 |
| Baricitinib | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 52 | -26.44 units on a scale | Standard Deviation 14.42 |
| Adalimumab | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 12 | -20.42 units on a scale | Standard Deviation 13.47 |
| Adalimumab | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 52 | -23.48 units on a scale | Standard Deviation 15.28 |
| Adalimumab | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Week 24 | -22.92 units on a scale | Standard Deviation 14.63 |
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, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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 | 0.073 units on a scale | Standard Deviation 0.151 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.065 units on a scale | Standard Deviation 0.168 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 52 | NA units on a scale | — |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.107 units on a scale | Standard Deviation 0.221 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.094 units on a scale | Standard Deviation 0.247 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 52 | NA units on a scale | — |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 52 | 0.215 units on a scale | Standard Deviation 0.235 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 12 | 0.132 units on a scale | Standard Deviation 0.156 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.188 units on a scale | Standard Deviation 0.228 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.203 units on a scale | Standard Deviation 0.244 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.143 units on a scale | Standard Deviation 0.168 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 52 | 0.152 units on a scale | Standard Deviation 0.163 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 24 | 0.137 units on a scale | Standard Deviation 0.167 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 52 | 0.141 units on a scale | Standard Deviation 0.189 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 52 | 0.198 units on a scale | Standard Deviation 0.273 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 12 | 0.186 units on a scale | Standard Deviation 0.232 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (US Algorithm) Week 12 | 0.130 units on a scale | Standard Deviation 0.159 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores | Index Score (UK Algorithm) Week 24 | 0.195 units on a scale | Standard Deviation 0.245 |
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, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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 24 | 5.6 millimeter | Standard Deviation 27.1 |
| 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 | 7.9 millimeter | Standard Deviation 26.2 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 52 | NA millimeter | — |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 24 | 17.5 millimeter | Standard Deviation 28.3 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 12 | 14.9 millimeter | Standard Deviation 25.8 |
| Baricitinib | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 52 | 19.9 millimeter | Standard Deviation 28 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 12 | 10.7 millimeter | Standard Deviation 26.9 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 52 | 13.3 millimeter | Standard Deviation 29.7 |
| Adalimumab | Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) | Self-Perceived Health Week 24 | 12.6 millimeter | Standard Deviation 28.9 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) 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, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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) Scale Scores | Week 24 | 6.6 units on a scale | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 12 | 6.8 units on a scale | Standard Deviation 9.9 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 52 | NA units on a scale | — |
| Baricitinib | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 24 | 10.4 units on a scale | Standard Deviation 10.8 |
| Baricitinib | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 12 | 9.6 units on a scale | Standard Deviation 10.4 |
| Baricitinib | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 52 | 10.8 units on a scale | Standard Deviation 10.9 |
| Adalimumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 12 | 9.5 units on a scale | Standard Deviation 10.1 |
| Adalimumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 52 | 9.8 units on a scale | Standard Deviation 10.8 |
| Adalimumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores | Week 24 | 9.9 units on a scale | Standard Deviation 11.2 |
Secondary
Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores
X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion).
Time frame: Baseline, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessment. Missing values due to discontinuation of study, rescue, or missing data were imputed using LE.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 24 (n= 452, 470, 312) | 0.27 units on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 24 (n=452, 470, 312) | 0.57 units on a scale | Standard Deviation 1.58 |
| Placebo | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 52 (n= 452, 473, 312) | 1.15 units on a scale | Standard Deviation 3.21 |
| Placebo | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 52 (n= 452, 473, 312) | 0.56 units on a scale | Standard Deviation 2.33 |
| Baricitinib | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 24 (n= 452, 470, 312) | 0.10 units on a scale | Standard Deviation 0.74 |
| Baricitinib | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 52 (n= 452, 473, 312) | 0.18 units on a scale | Standard Deviation 1.02 |
| Baricitinib | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 24 (n=452, 470, 312) | 0.25 units on a scale | Standard Deviation 1.12 |
| Baricitinib | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 52 (n= 452, 473, 312) | 0.42 units on a scale | Standard Deviation 1.91 |
| Adalimumab | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 24 (n=452, 470, 312) | 0.20 units on a scale | Standard Deviation 1.08 |
| Adalimumab | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 24 (n= 452, 470, 312) | 0.09 units on a scale | Standard Deviation 0.52 |
| Adalimumab | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Joint Space Narrowing Week 52 (n= 452, 473, 312) | 0.17 units on a scale | Standard Deviation 1 |
| Adalimumab | Change From Baseline in Joint Space Narrowing (JSN) and Bone Erosion Scores | Bone Erosion Score Week 52 (n= 452, 473, 312) | 0.34 units on a scale | Standard Deviation 2 |
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, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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) | MCS Week 12 | 3.2 units on a scale | Standard Deviation 10.3 |
| 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) | MCS Week 24 | 2.2 units on a scale | Standard Deviation 11.4 |
| 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) | MCS Week 52 | NA units on a scale | — |
| 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) | PCS Week 12 | 4.3 units on a scale | Standard Deviation 7.1 |
| 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) | PCS Week 24 | 4.6 units on a scale | Standard Deviation 7.8 |
| 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) | PCS Week 52 | NA units on a scale | — |
| Baricitinib | 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) | PCS Week 52 | 10.4 units on a scale | Standard Deviation 9 |
| Baricitinib | 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) | MCS Week 12 | 3.3 units on a scale | Standard Deviation 10.5 |
| Baricitinib | 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) | PCS Week 12 | 8.9 units on a scale | Standard Deviation 8.1 |
| Baricitinib | 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) | PCS Week 24 | 9.9 units on a scale | Standard Deviation 8.2 |
| Baricitinib | 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) | MCS Week 24 | 3.8 units on a scale | Standard Deviation 10.9 |
| Baricitinib | 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) | MCS Week 52 | 4.0 units on a scale | Standard Deviation 10.8 |
| Adalimumab | 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) | MCS Week 24 | 3.9 units on a scale | Standard Deviation 11.6 |
| Adalimumab | 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) | MCS Week 52 | 3.7 units on a scale | Standard Deviation 11.2 |
| Adalimumab | 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) | PCS Week 52 | 9.0 units on a scale | Standard Deviation 9.2 |
| Adalimumab | 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) | PCS Week 12 | 7.6 units on a scale | Standard Deviation 8.2 |
| Adalimumab | 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) | MCS Week 12 | 3.8 units on a scale | Standard Deviation 10.8 |
| Adalimumab | 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) | PCS Week 24 | 8.3 units on a scale | Standard Deviation 9.1 |
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 includes 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) | -1.01 units on a scale | Standard Deviation 1.12 |
| Baricitinib | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | -2.27 units on a scale | Standard Deviation 1.22 |
| Adalimumab | Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) | -1.98 units on a scale | Standard Deviation 1.28 |
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 includes 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 | -0.33 units on a scale | Standard Deviation 0.51 |
| Baricitinib | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | -0.65 units on a scale | Standard Deviation 0.59 |
| Adalimumab | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | -0.56 units on a scale | Standard Deviation 0.54 |
Secondary
Change From Baseline in the Modified Total Sharp Score (mTSS)
X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS. This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448.
Time frame: Baseline, Week 24
Population: mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessments. Missing values due to discontinuation of study, rescue, or missing data were imputed using linear extrapolation (LE).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Modified Total Sharp Score (mTSS) | 0.84 units on a scale | Standard Deviation 2.32 |
| Baricitinib | Change From Baseline in the Modified Total Sharp Score (mTSS) | 0.35 units on a scale | Standard Deviation 1.59 |
| Adalimumab | Change From Baseline in the Modified Total Sharp Score (mTSS) | 0.29 units on a scale | Standard Deviation 1.47 |
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, Week 24, Week 52
Population: mITT population includes all randomized participants who received at least 1 dose of the study drug, 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 (n=160,168,118) | 0.5 percentage of impairment | Standard Deviation 27.7 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 (n=118,139,102) | -1.6 percentage of impairment | Standard Deviation 24.5 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 52 (n=0,124,92) | NA percentage of impairment | — |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 (n=147,160,113) | -11 percentage of impairment | Standard Deviation 23 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 (n=110,134,99) | -11 percentage of impairment | Standard Deviation 22 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 52 (n=0,119,88) | NA percentage of impairment | — |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 (n=147,160,113) | -10.4 percentage of impairment | Standard Deviation 24.3 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 (n=110,134,99) | -9.0 percentage of impairment | Standard Deviation 24.9 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 52 (n=0,119,88) | NA percentage of impairment | — |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 (n=458,474,315) | -11 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 (n=333,430,272) | -16 percentage of impairment | Standard Deviation 26 |
| Placebo | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 52 (n=0,396,240) | NA percentage of impairment | — |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 52 (n=0,396,240) | -30 percentage of impairment | Standard Deviation 27 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 (n=160,168,118) | -4.9 percentage of impairment | Standard Deviation 20.6 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 (n=147,160,113) | -21.6 percentage of impairment | Standard Deviation 28 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 52 (n=0,119,88) | -24.4 percentage of impairment | Standard Deviation 30.1 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 (n=118,139,102) | -1.8 percentage of impairment | Standard Deviation 25.2 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 52 (n=0,119,88) | -25 percentage of impairment | Standard Deviation 27 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 (n=333,430,272) | -28 percentage of impairment | Standard Deviation 27 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 52 (n=0,124,92) | -3.8 percentage of impairment | Standard Deviation 25.1 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 (n=110,134,99) | -22.1 percentage of impairment | Standard Deviation 30.2 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 (n=110,134,99) | -23 percentage of impairment | Standard Deviation 27 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 (n=147,160,113) | -21 percentage of impairment | Standard Deviation 26 |
| Baricitinib | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 (n=458,474,315) | -25 percentage of impairment | Standard Deviation 26 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 12 (n=147,160,113) | -16 percentage of impairment | Standard Deviation 24 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 24 (n=110,134,99) | -22 percentage of impairment | Standard Deviation 26 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 12 (n=458,474,315) | -20 percentage of impairment | Standard Deviation 25 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Presenteeism Week 52 (n=0,119,88) | -25 percentage of impairment | Standard Deviation 27 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 12 (n=147,160,113) | -14.0 percentage of impairment | Standard Deviation 25.6 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 24 (n=110,134,99) | -21.4 percentage of impairment | Standard Deviation 27.2 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 24 (n=333,430,272) | -26 percentage of impairment | Standard Deviation 26 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 12 (n=160,168,118) | -0.5 percentage of impairment | Standard Deviation 25.7 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 24 (n=118,139,102) | -3.2 percentage of impairment | Standard Deviation 23.8 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Work Productivity Loss Week 52 (n=0,119,88) | -24.6 percentage of impairment | Standard Deviation 29.8 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Absenteeism Week 52 (n=0,124,92) | -3.7 percentage of impairment | Standard Deviation 24.3 |
| Adalimumab | Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores | Activity Impairment Week 52 (n=0,396,240) | -28 percentage of impairment | Standard Deviation 27 |
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 morning joint stiffness by selecting a number from 0 to 10 that best described their overall level of morning joint stiffness 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 was calculated.
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 | 4.1 units on a scale | Standard Deviation 2.3 |
| Baricitinib | Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.0 units on a scale | Standard Deviation 2.2 |
| Adalimumab | 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 2.3 |
Secondary
Mean Worst Joint Pain 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 was calculated.
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 NRS in the Prior 7 Days as Collected in Electronic Diaries | 4.6 units on a scale | Standard Deviation 2.2 |
| Baricitinib | Mean Worst Joint Pain NRS in the Prior 7 Days as Collected in Electronic Diaries | 3.4 units on a scale | Standard Deviation 2.2 |
| Adalimumab | Mean Worst Joint Pain NRS in the Prior 7 Days as Collected in Electronic Diaries | 4.0 units on a scale | Standard Deviation 2.3 |
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 worst tiredness during the last 24 hours, where 0 represents no tiredness and 10 represents as bad as you can imagine. Participants reported their worst tiredness in electronic diaries. The average value across the 7 days preceding each visit is calculated.
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 | 4.4 units on a scale | Standard Deviation 2.3 |
| Baricitinib | Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.6 units on a scale | Standard Deviation 2.2 |
| Adalimumab | Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries | 3.9 units on a scale | Standard Deviation 2.3 |
Secondary
Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries
Participants recorded the duration of their morning joint stiffness (MJS) in hours and minutes into electronic diaries daily. If morning joint stiffness 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 was calculated. A decrease in duration of morning joint stiffness 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 | Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries | 60.0 Minutes |
| Baricitinib | Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries | 27.1 Minutes |
| Adalimumab | Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries | 36.6 Minutes |
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
ACR50 and ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR50 and ACR70 Responder is a participant who has at least 50% or 70% improvement, respectively, 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 discontinued study or drug or were rescued before analysis time point were deemed non-responders.
Time frame: Week 12, Week 24, Week 52
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) and 70% (ACR70) Response | ACR50 Week 24 | 19.3 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 52 | NA percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 24 | 8.0 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 12 | 16.8 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 12 | 4.7 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 52 | NA percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 12 | 18.9 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 24 | 29.8 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 52 | 37.2 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 24 | 50.5 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 52 | 55.9 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 12 | 45.0 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 52 | 30.6 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 24 | 45.5 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 12 | 34.8 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR50 Week 52 | 47.0 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 12 | 12.7 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response | ACR70 Week 24 | 21.8 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, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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 European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 24 | 2.7 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 12 | 1.0 percentage of participants |
| Placebo | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 52 | NA percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 24 | 12.1 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 12 | 7.2 percentage of participants |
| Baricitinib | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 52 | 15.6 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 12 | 5.2 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 52 | 13.0 percentage of participants |
| Adalimumab | Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission | Week 24 | 10.0 percentage of participants |
Secondary
Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤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), Patient'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, Week 24, Week 52
Population: mITT population: all randomized participants who received at least 1 dose of 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 Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 24 | 3.1 percentage of participants |
| Placebo | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 12 | 1.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 52 | NA percentage of participants |
| Baricitinib | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 24 | 16.0 percentage of participants |
| Baricitinib | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 12 | 8.4 percentage of participants |
| Baricitinib | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 52 | 22.6 percentage of participants |
| Adalimumab | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 12 | 7.3 percentage of participants |
| Adalimumab | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 52 | 17.9 percentage of participants |
| Adalimumab | Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3 | Week 24 | 13.6 percentage of participants |
Secondary
Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib
Time frame: Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 12; Week 24; Week 32: 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 Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib | 143 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 19.7 |
Secondary
Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
Time frame: Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 12; Week 24; Week 32: 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 Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib | 1220 nanomole*hr/Liter (nmol*hr/L) | Geometric Coefficient of Variation 45.8 |