An Extension Study in Participants With Moderate to Severe Rheumatoid Arthritis (RA-BEYOND)

• ClinicalTrials.gov Identifier: NCT01885078
• Recruitment Status: Completed
• First Posted: June 24, 2013
• Results First Posted: February 1, 2022
• Last Update Posted: April 25, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: June 19, 2013
• First Posted Date: June 24, 2013
• Results First Submitted Date: November 11, 2021
• Results First Posted Date: February 1, 2022
• Last Update Posted Date: April 25, 2022
• Actual Study Start Date: June 27, 2013
• Actual Primary Completion Date: November 12, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 2022)

Number of Participants Who Experienced Adverse Events (AEs) or Serious AE [ Time Frame: Baseline through 84 Months ]

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (i.e., abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Non-serious AEs are reported at a threshold of 5%. An SAE is an AE from this study that results in any of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability/incapacity, congenital anomaly/birth defect, considered significant by the investigator for any other reason A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.

• Original Primary Outcome Measures (submitted: June 19, 2013): Number of Participants with One or More Drug Related Adverse Events (AEs) or any Serious AEs [ Time Frame: Baseline through 2 Years ]

Current Secondary Outcome Measures (submitted: January 2, 2022)

• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20 [ Time Frame: Year 1 after entry into JADY ]
  ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20 [ Time Frame: Year 3 after entry into JADY ]
  ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20 [ Time Frame: Year 5 after entry into JADY ]
  ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR50 [ Time Frame: Year 1 after entry into JADY ]
  ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR50 [ Time Frame: Year 3 after entry into JADY ]
  ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR50 [ Time Frame: Year 5 after entry into JADY ]
  ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR70 [ Time Frame: Year 1 after entry into JADY ]
  ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR70 [ Time Frame: Year 3 after entry into JADY ]
  ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR70 [ Time Frame: Year 5 after entry into JADY ]
  ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) ≤3.2 [ Time Frame: Year 1 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) ≤3.2 [ Time Frame: Year 3 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP) ≤3.2 [ Time Frame: Year 5 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP)<2.6 [ Time Frame: Year 1 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP)<2.6 [ Time Frame: Year 3 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a Disease Activity Score (DAS28) High-Sensitivity C-Reactive Protein (hsCRP)<2.6 [ Time Frame: Year 5 after entry into JADY ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). 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 from 1.0-9.4, where lower scores indicated less disease activity, low disease activity was DAS28-CRP ≤3.2 and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Score of ≤3.2 [ Time Frame: Year 1 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Score of ≤3.2 [ Time Frame: Year 3 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Score of ≤3.2 [ Time Frame: Year 5 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Sore of <2.6 [ Time Frame: Year 1 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Sore of <2.6 [ Time Frame: Year 3 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a DAS28-Erythrocyte Sedimentation Rate (ESR) Sore of <2.6 [ Time Frame: Year 5 after entry into JADY ]
  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.
• Percentage of Participants Maintaining American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission Response [ Time Frame: Year 1 after entry into JADY ]
  Boolean-based definition of remission, all 4 criteria below must be met: tender joint count (TJC28 ) <=1, swollen joint count (SJC28) <=1, hsCRP <=1 milligram per deciliter (mg/dL), Patient Global Assessment of Disease Activity using visual analog scale (VAS) <=1 cm.
• Percentage of Participants Maintaining American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission Response [ Time Frame: Year 3 after entry into JADY ]
  Boolean-based definition of remission, all 4 criteria below must be met: tender joint count (TJC28 ) <=1, swollen joint count (SJC28) <=1, hsCRP <=1 milligram per deciliter (mg/dL), Patient Global Assessment of Disease Activity using visual analog scale (VAS) <=1 cm.
• Percentage of Participants Maintaining American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission Response [ Time Frame: Year 5 after entry into JADY ]
  Boolean-based definition of remission, all 4 criteria below must be met: tender joint count (TJC28 ) <=1, swollen joint count (SJC28) <=1, hsCRP <=1 milligram per deciliter (mg/dL), Patient Global Assessment of Disease Activity using visual analog scale (VAS) <=1 cm.
• Change From Baseline of Originating Study in Modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Year 1 ]
  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 (JSN) 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. Least Squares Mean (LSM) was calculated using a mixed model for repeated measures (MMRM) with treatment, visit, treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
• Change From Baseline of Originating Study in Modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Year 3 ]
  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 (JSN) 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. Least Squares Mean (LSM) was calculated using a mixed model for repeated measures (MMRM) with treatment, visit, treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
• Change From Baseline of Originating Study in Modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Year 5 ]
  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 (JSN) 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. Least Squares Mean (LSM) was calculated using a mixed model for repeated measures (MMRM) with treatment, visit, treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
• Percentage of Participants With mTSS Change ≤0 [ Time Frame: Year 1 after entry into JADY ]
  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 (JSN) 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, with higher scores representing greater damage.
• Percentage of Participants With mTSS Change ≤0 [ Time Frame: Year 3 after entry into JADY ]
  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 (JSN) 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, with higher scores representing greater damage.
• Percentage of Participants With mTSS Change ≤0 [ Time Frame: Year 5 after entry into JADY ]
  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 (JSN) 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, with higher scores representing greater damage.
• Change From Baseline of Originating Study in Joint Space Narrowing at Year 1 [ Time Frame: Baseline, Year 1 ]
  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.
• Change From Baseline of Originating Study in Joint Space Narrowing at Year 3 [ Time Frame: Baseline, Year 3 ]
  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.
• Change From Baseline of Originating Study in Joint Space Narrowing at Year 5 [ Time Frame: Baseline, Year 5 ]
  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
• Change From Baseline of Originating Study in Duration of Morning Stiffness [ Time Frame: Baseline, Year 1 ]
  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 the day of the study visit. 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 of Originating Study in Duration of Morning Stiffness [ Time Frame: Baseline, Year 3 ]
  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 the day of the study visit. 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 of Originating Study in Duration of Morning Stiffness [ Time Frame: Baseline, Year 5 ]
  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 the day of the study visit. 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 of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores [ Time Frame: Baseline, Year 1 ]
  The 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.
• Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores [ Time Frame: Baseline, Year 3 ]
  The 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.
• Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores [ Time Frame: Baseline, Year 5 ]
  The 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.
• Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) [ Time Frame: Baseline, Year 1 ]
  The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. 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.
• Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) [ Time Frame: Baseline, Year 3 ]
  The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. 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.
• Change From Baseline of Originating Study in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) [ Time Frame: Baseline, Year 5 ]
  The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. 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 of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10 [ Time Frame: Year 1 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10 [ Time Frame: Year 3 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10 [ Time Frame: Years 5 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤ 2.8 [ Time Frame: Year 1 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤2.8 [ Time Frame: Year 3 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤2.8 [ Time Frame: Year 5 after entry into JADY ]
  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.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.22 [ Time Frame: Year 1 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.22 [ Time Frame: Year 3 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.22 [ Time Frame: Year 5 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.3 [ Time Frame: Year 1 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.3 [ Time Frame: Year 3 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Percentage of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement ≥0.3 [ Time Frame: Year 5 after entry into JADY ]
  The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. An improvement of 0.22 or 0.3 points on the HAQ-DI has been identified as a minimal clinically important difference in Rheumatoid Arthritis participants.
• Change From Baseline of Originating Study in Bone Erosion Score [ Time Frame: Baseline, Year 1 ]
  The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. The maximum erosion score for a hand joint is 5 and for a foot joint is 10. Thus, the maximal erosion score is 280 for a timepoint (160 for both hands/ wrists and 120 for both 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. The highest score (5 for the hand and 10 for the foot) indicates extensive loss of bone from more than one half of the articulating bone. A score of 0 in either the hand or foot joints indicates no erosion. LSM was calculated using an MMRM model with treatment, baseline value, visit, and the interactions of baseline-by-visit and treatment-by-visit as fixed factors.
• Change From Baseline of Originating Study in Bone Erosion Score [ Time Frame: Baseline, Year 3 ]
  The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. The maximum erosion score for a hand joint is 5 and for a foot joint is 10. Thus, the maximal erosion score is 280 for a timepoint (160 for both hands/ wrists and 120 for both 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. The highest score (5 for the hand and 10 for the foot) indicates extensive loss of bone from more than one half of the articulating bone. A score of 0 in either the hand or foot joints indicates no erosion. LSM was calculated using an MMRM model with treatment, baseline value, visit, and the interactions of baseline-by-visit and treatment-by-visit as fixed factors.
• Change From Baseline of Originating Study in Bone Erosion Score [ Time Frame: Baseline, Year 5 ]
  The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. The maximum erosion score for a hand joint is 5 and for a foot joint is 10. Thus, the maximal erosion score is 280 for a timepoint (160 for both hands/ wrists and 120 for both 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. The highest score (5 for the hand and 10 for the foot) indicates extensive loss of bone from more than one half of the articulating bone. A score of 0 in either the hand or foot joints indicates no erosion. LSM was calculated using an MMRM model with treatment, baseline value, visit, and the interactions of baseline-by-visit and treatment-by-visit as fixed factors.
• Healthcare Resource Utilization [ Time Frame: Baseline up to 84 Months ]
  Number of visits to medical care providers related to treatment of Rheumatoid Arthritis (RA) outside of the clinical study. Reported here are healthcare consultations and emergency room consultations from end of originating study to end of participation in study JADY.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤11 [ Time Frame: Year 1 after entry into JADY ]
  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). Low disease activity is defined as a SDAI score ≤11.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤11 [ Time Frame: Year 3 after entry into JADY ]
  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). Low disease activity is defined as a SDAI score ≤11.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤11 [ Time Frame: Year 5 after entry into JADY ]
  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). Low disease activity is defined as a SDAI score ≤11.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤3.3 [ Time Frame: Year 1 after entry into JADY ]
  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). Disease remission is defined as an SDAI score of ≤3.3.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤3.3 [ Time Frame: Year 3 after entry into JADY ]
  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). Disease remission is defined as an SDAI score of ≤3.3.
• Percentage of Participants Maintaining a Simplified Disease Activity Index (SDAI) ≤3.3 [ Time Frame: Year 5 after entry into JADY ]
  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). Disease remission is defined as an SDAI score of ≤3.3.
• Percentage of Participants With Relapse Event During the 96-Week Step-Down Period [ Time Frame: Week 0 through Week 96 of Step-down ]
  Relapse is defined as a Clinical Disease Activity Index score > 10. 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. Total number of participants at risk multiplied by estimate of cumulative event probability would need to be rounded up or down to get a whole number.

Original Secondary Outcome Measures (submitted: June 19, 2013)

• Proportion of Participants Maintaining an American College of Rheumatology (ACR) Response of ACR20, ACR50, and ACR70 [ Time Frame: Baseline through Months 12, 24, 36, 48, 54 ]
• Proportion of Participants Maintaining a Disease Activity Score (DAS28) high-sensitivity C-Reactive Protein (hsCRP)/DAS28-Erythrocyte Sedimentation Rate (ESR) ≤3.2 [ Time Frame: Baseline through Months 12, 24, 36, 48, 54 ]
• Change from Baseline in modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Month 12, 24, 36, 48 ]
• Proportion of Participants with mTSS change ≤0 [ Time Frame: Baseline through Months 12, 24, 36, 48 ]
• Change from Baseline in Joint Space Narrowing [ Time Frame: Baseline, Month 12, 24, 36, 48 ]
• Change from Baseline in Duration of Morning Stiffness [ Time Frame: Baseline, Month 12, 24, 36, 48, 54 ]
• Change from Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores [ Time Frame: Baseline, 2 Years ]
• Proportion of Participants Maintaining a Clinical Disease Activity Index Score (CDAI) ≤10 [ Time Frame: Baseline through Months 12, 24, 36, 48, 54 ]
• Proportion of Participants Maintaining a Health Assessment Questionnaire Disability Index (HAQ-DI) Improvement of ≥0.22 and ≥0.3 [ Time Frame: Baseline through Months 12, 24, 36, 48, 54 ]
• Change from Baseline in Bone Erosion Score [ Time Frame: Baseline, Month 12, 24, 36, 48 ]
• Healthcare Resource Utilization [ Time Frame: Baseline through 2 Years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study in Participants With Moderate to Severe Rheumatoid Arthritis
• Official Title: A Phase 3, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Patients With Rheumatoid Arthritis

Brief Summary

The purpose of this study is to investigate the long-term safety and any side effects of baricitinib in participants who have completed a previous baricitinib rheumatoid arthritis study.

The study provides 7 years of additional treatment with baricitinib.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: Baricitinib
  Administered orally
  Other Names:

  • LY 3009104
  • INCB 028050
• Drug: Placebo
  Administered orally

Study Arms

• Experimental: 4 milligram (mg) Baricitinib

  4 mg Baricitinib administered orally once daily.

  Participants received baricitinib doses according to the dose received at the completion of the originating study. Participants may continue to receive the background non-investigational, open-label conventional disease-modifying antirheumatic drugs (cDMARD), nonsteroidal anti-inflammatory drug (NSAID), corticosteroid, and other analgesic therapies they were receiving at completion of the originating study.

  Interventions:

  • Drug: Baricitinib
  • Drug: Placebo
• Experimental: 2 mg Baricitinib

  2 mg Baricitinib administered orally once daily.

  Participants received baricitinib doses according to the dose received at the completion of the originating study. Participants may continue to receive the background non-investigational, open-label cDMARD, NSAID, corticosteroid, and other analgesic therapies they were receiving at completion of the originating study.

  Interventions:

  • Drug: Baricitinib
  • Drug: Placebo
• Experimental: 2 mg Baricitinib Step-down

  2 mg Baricitinib administered orally once daily in the 96-week Step-down period.

  Participants may continue to receive the background non-investigational, open-label cDMARD, NSAID, corticosteroid, and other analgesic therapies they were receiving at completion of the originating study.

  Intervention: Drug: Baricitinib
• Experimental: 4 mg Baricitinib Step-down

  4 mg Baricitinib administered orally once daily in the 96-week Step-down period.

  Participants may continue to receive the background non-investigational, open-label cDMARD, NSAID, corticosteroid, and other analgesic therapies they were receiving at completion of the originating study.

  Intervention: Drug: Baricitinib

Publications *

• Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.
• Wells AF, Jia B, Xie L, Valenzuela GJ, Keystone EC, Li Z, Quebe AK, Griffing K, Otawa S, Haraoui B. Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study. Rheumatol Ther. 2021 Jun;8(2):987-1001. doi: 10.1007/s40744-021-00317-9. Epub 2021 May 24.
• Fleischmann R, Takeuchi T, Schiff M, Schlichting D, Xie L, Issa M, Stoykov I, Lisse J, Martinez-Osuna P, Rooney T, Zerbini CAF. Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus Methotrexate. Arthritis Care Res (Hoboken). 2020 Aug;72(8):1112-1121. doi: 10.1002/acr.24007.
• Tanaka Y, Fautrel B, Keystone EC, Ortmann RA, Xie L, Zhu B, Issa M, Patel H, Gaich CL, de Bono S, Rooney TP, Taylor PC. Clinical outcomes in patients switched from adalimumab to baricitinib due to non-response and/or study design: phase III data in patients with rheumatoid arthritis. Ann Rheum Dis. 2019 Jul;78(7):890-898. doi: 10.1136/annrheumdis-2018-214529. Epub 2019 Apr 30.
• Winthrop KL, Bingham CO 3rd, Komocsar WJ, Bradley J, Issa M, Klar R, Kartman CE. Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy. Arthritis Res Ther. 2019 Apr 18;21(1):102. doi: 10.1186/s13075-019-1883-1.
• Smolen JS, Genovese MC, Takeuchi T, Hyslop DL, Macias WL, Rooney T, Chen L, Dickson CL, Riddle Camp J, Cardillo TE, Ishii T, Winthrop KL. Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment. J Rheumatol. 2019 Jan;46(1):7-18. doi: 10.3899/jrheum.171361. Epub 2018 Sep 15. Erratum In: J Rheumatol. 2019 Dec;46(12):1648-1649.
• Tanaka Y, McInnes IB, Taylor PC, Byers NL, Chen L, de Bono S, Issa M, Macias WL, Rogai V, Rooney TP, Schlichting DE, Zuckerman SH, Emery P. Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis. Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680. Epub 2018 Oct 22.
• Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 2, 2022): 2877
• Original Estimated Enrollment (submitted: June 19, 2013): 2347
• Actual Study Completion Date: November 12, 2020
• Actual Primary Completion Date: November 12, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have completed the final active treatment in study JADV (NCT01710358), JADZ (NCT01711359), JADX (NCT01721057), JADW (NCT01721044), JADA (NCT01185353) or JAGS (NCT02265705)

Exclusion Criteria:

• Have significant uncontrolled cerebro-cardiovascular (eg, myocardial infarction [MI], unstable angina, unstable arterial hypertension, severe heart failure, or cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or abnormal laboratory values that developed during a previous baricitinib study that, in the opinion of the investigator, pose an unacceptable risk to the participant if investigational product continues to be administered
• Have a known hypersensitivity to baricitinib or any component of this investigational product
• Had investigational product permanently discontinued at any time during a previous baricitinib study
• Had temporary investigational product interruption at the final study visit of a previous baricitinib study and, in the opinion of the investigator, this poses an unacceptable risk for participation in the study
• Have any other condition that, in the opinion of the investigator, renders the participant unable to understand the nature, scope, and possible consequences of the study or precludes the participant from following and completing the protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01885078
• Other Study ID Numbers: 14060; I4V-MC-JADY ( Other Identifier: Eli Lilly and Company ); 2012-003686-17 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2022