A Study To Compare The Effectiveness Of Tofacitinib 11 Mg Once A Day To Tofacitinib 5 Mg Twice A Day

Study Overview
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Brief Summary
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It is hypothesized that patients prescribed tofacitinib 11 mg Modified Release (MR) formulation once daily (QD) will achieve similar benefit to those prescribed tofacitinib 5 mg twice a day (BID) dosage in real world use. This study will therefore seek to compare the effectiveness of the MR 11 mg QD regimen to the IR 5 mg BID regimen for the treatment of RA in a real-world registry of RA patients.

Official Title
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Compare Effectiveness of Tofacitinib 11 mg QD to Tofacitinib 5 mg BID

Conditions
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Arthritis Rheumatoid

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All US Corrona RA Registry patients who initiated tofacitinib 5 mg twice a day (BID) or tofacitinib 11 mg once daily (QD) after it became available in February 2016 Patients must have a follow-up visit at 6 months (+/- 3 months) after tofacitinib initiation. These 6 month visits are part of routine practice and is not associated with this protocol. Patients must have a valid clinical disease activity index (CDAI) at initiation and at 6-month follow-up visit Exclusion Criteria: There are no exclusion criteria for this study.

Ages Eligible for Study
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Minimum Age: 0 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Corrona US RA Registry 11 mg<br>patients with RA who have been exposed to tofacitinib 11 mg QD tablet | |
| Corrona US RA Registry 5 mg<br>patients with RA who have been exposed to tofacitinib 5 mg BID tablet | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Minimally Clinically Important Difference (MCID) Improvement From Baseline Upto 6 Months | MCID improvement assessed based on Clinical disease activity index (CDAI). CDAI: numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment (PtGA) and physician global assessment (PGA) assessed on 0-10 centimeter (cm) Visual analogue scale (VAS); CDAI total score = 0-76, higher scores=greater affection due to disease activity (DA). CDAI less than or equal to (<=) 2.8 indicates disease remission, greater than (>) 2.8 to 10 = low DA, >10 to 22 = moderate DA, and >22 = high DA. MCID improvement defined by difference in CDAI from baseline (at time of tofacitinib initiation) to 6 month visit. Participants were considered to show improvement from baseline on 3 cut points (1) greater than or equal (>=) to 2 (for participants in low DA at baseline); (2) >= 6 (moderate DA at baseline, and (3) >= 11 (high DA at baseline). Here, overall number of participants who showed improvement have been reported. | Baseline Up to 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Month 6 | CDAI is the numerical sum of 4 outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 to 10 cm VAS; CDAI total score = 0 to 76, higher scores=greater affection due to disease activity. CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Here, all participants who achieved remission (CDAI <=2.8) at Month 6 have been reported. | Baseline, Month 6 | 
| Number of Participants Achieving Remission at Month 6 (All Participants) | CDAI is the numerical sum of 4 outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 to 10 cm VAS; CDAI total score = 0 to 76, higher scores=greater affection due to disease activity. CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Here, all participants who achieved remission (CDAI <=2.8) at Month 6 have been reported. | Month 6 | 
| Number of Participants Achieving Remission at Month 6 (For Participants With Baseline CDAI >2.8) | CDAI is the numerical sum of 4 outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 to 10 cm VAS; CDAI total score = 0 to 76, higher scores=greater affection due to disease activity. CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Here, only those participants who had baseline CDAI greater than 2.8, and who achieved remission (CDAI <= 2.8) at Month 6 have been reported. | Month 6 | 
| Number of Participants Achieving Low Disease Activity at Month 6 (All Participants) | CDAI is the numerical sum of 4 outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 to 10 cm VAS; CDAI total score = 0 to 76, higher scores=greater affection due to disease activity. CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Here, all participants who achieved low disease activity (CDAI > 2.8 to 10) at Month 6 have been reported. | Month 6 | 
| Number of Participants Achieving Low Disease Activity at Month 6 (Participants With Baseline CDAI >10) | CDAI is the numerical sum of 4 outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 to 10 cm VAS; CDAI total score = 0 to 76, higher scores=greater affection due to disease activity. CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity. Here, only those participants who had baseline CDAI greater than 10, and who achieved low disease activity (CDAI > 2.8 to 10) at Month 6 have been reported. | Month 6 | 
| Number of Participants With Decrease From Baseline in Modified Health Assessment Questionnaire (mHAQ) Score at Month 6 | Modified HAQ: participant-reported questionnaire for the assessment of ability to perform tasks due to rheumatoid arthritis. It comprised of 8 questions on 8 categories of daily living activities: dress/groom; arise; eat; grip; walk; hygiene; reach; and common activities over past week before specified time point. Eight items were rated on a 4-point Likert scale from 0 to 3, where 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranged from 0 to 3, where 0 = least difficulty and 3 = extreme difficulty, higher scores indicating worse functioning. Participants who had a baseline mHAQ score of >=0.25 were evaluable for this outcome measure and number of participants who had decrease from baseline in mHAQ score at Month 6 were reported. | Month 6 | 
| Number of Participants With Decrease From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 6 | HAQ: participant-reported questionnaire for the assessment of rheumatoid arthritis. It comprised of 20 questions in 8 categories of activities: dress/groom; arise; eat; grip; walk; hygiene; reach; and activities over past week. Each activity was assessed on a 4-point Likert scale from 0 to 3, where 0 = without difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranged from 0 to 3, where 0 = least difficulty and 3 = extreme difficulty, higher scores indicating worse functioning. Participants who had a baseline HAQ score of >=0.22 were evaluable for this outcome measure and number of participants who had decrease from baseline in HAQ score at Month 6 were reported. | Month 6 | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 6: Dichotomous Variable |  | Baseline, Month 6 | 
| Change From Baseline in Modified Health Assessment Questionnaire (mHAQ) Score at Month 6 | Modified HAQ: participant-reported questionnaire for the assessment of ability to perform tasks due to rheumatoid arthritis. It comprised of 8 questions in 8 categories of daily living activities: dress/groom; arise; eat; grip; walk; hygiene; reach; and common activities over past week. Eight item were rated on a 4-point Likert scale from 0 to 3, where 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranged from 0 to 3, where 0 = least difficulty and 3 = extreme difficulty, higher scores indicating worse functioning. | Baseline, Month 6 | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 6 | HAQ: participant-reported questionnaire for the assessment of rheumatoid arthritis. It comprised of 20 questions in 8 categories of activities: dress/groom; arise; eat; grip; walk; hygiene; reach; and activities over past week. Each activity was assessed on a 4-point Likert scale from 0 to 3, where 0 = without difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranged from 0 to 3, where 0 = least difficulty and 3 = extreme difficulty, higher scores indicating worse functioning. | Baseline, Month 6 | 
| Change From Baseline in Modified Disease Activity Score Based on 28-joints Count (mDAS28) at Month 6 | Modified DAS28: Indicator of disease activity calculated as weighted average of six components: tender joint counts (TJC), swollen joint counts (SJC), mHAQ measure of disease activity, participant reported pain, physician reported global health assessment (PGA) and participant reported global health assessment (PtGA). TJC and SJC calculated using 28 joints count; mHAQ scored on a scale of 0 to 3 (0 = least difficulty, 3 = extreme difficulty); participant reported pain scored on a scale of 0 to 100 (0 = no pain, 100= pain as bad as it could be); PGA and PtGA recorded on a visual analog scale (VAS) of 0 millimeter (mm) to 100 mm (0 = no disease activity and 100=high disease activity). Transformed mDAS28 score ranged from 0 to 9.4, where higher scores indicated more disease activity. | Baseline, Month 6 | 
| Change From Baseline in Disease Activity Score Based on 28-joints Count (DAS28) Erythrocyte Sedimentation Rate (ESR) at Month 6 | DAS28 is a measure of disease activity in participants with rheumatoid arthritis, derived using differential weighting given to each of the four components. The components of the DAS28 (ESR) assessment included: TJC with 28 joints assessed, SJC with 28 joints assessed, ESR (millimeters per hour) and PtGA recorded on 100mm VAS (scores ranging 0 [very well] to 100 mm [extremely bad]). DAS28 (ESR) was calculated as 0.56*sqrt (TJC28) + 0.28*sqrt (SJC28) + 0.70*ln(ESR [mm/hour] + 0.014*PtGA [mm]; where, ln = natural logarithm, sqrt = square root of. Total score range: 0 to 9.4, higher score indicated more disease activity. | Baseline, Month 6 | 
| Change From Baseline in Disease Activity Score Based on 28-joints Count (DAS28) C- Reactive Protein (CRP) at 6 Month | DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter [mg/L]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). DAS28 (CRP) was calculated as = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96.Total DAS28 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. | Baseline, 6 months | 
| Change From Baseline in Participant Pain Score at Month 6 | Participants were asked the following question to answer on a numeric rating scale (NRS): How much pain have you had because of your arthritis in the past week? The scale ranged from 0-100, where 0=no pain and 100=pain as bad as it could be. Higher scores indicated worsening of condition. | Baseline, Month 6 | 
| Change From Baseline in Participant Fatigue Score at Month 6 | Participants were asked the following question to answer on NRS: How much of a problem has unusual fatigue of tiredness been for you in the past week? The scale ranged from 0-100, where 0=no fatigue and 100=fatigue as bad as it could be. Higher scores indicated worsening of condition. | Baseline, Month 6 | 
| Change From Baseline in European Quality of Life- 5 Dimension (EQ-5D) Index at Month 6 | EQ-5D index: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. It assesses level of current health in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension had 3 levels: no problems (1), some problems (2) and severe problems (3). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range 0 to 1, where 0=death and 1=perfect health; higher score indicates a better health state. | Baseline, Month 6 | 
| Number of Participants Achieving Modified American College of Rheumatology 20% (mACR20) Response | mACR20 response: >= 20 percent (%) improvement in tender and swollen joint count and 20% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain) ; 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the mHAQ (scored from 0 to 3, higher scores indicated worsening of function). | Month 6 | 
| Number of Participants Achieving Modified American College of Rheumatology 50% (mACR50) Response | mACR50 response: >= 50% improvement in tender and swollen joint count and 50% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain) ; 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the mHAQ (scored from 0 to 3, higher scores indicated worsening of function). | Month 6 | 
| Number of Participants Achieving Modified American College of Rheumatology 70% (mACR70) Response | mACR70 response: >= 70% improvement in tender and swollen joint count and 70% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain) ; 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the mHAQ (scored from 0 to 3, higher scores indicated worsening of function). | Month 6 |