Comparative Effectiveness Of Tumor Necrosis Factor Inhibitors And Tofacitinib Use In Earlier Lines Of Therapy And Use As Monotherapy.

Study Overview
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Brief Summary
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This study is to investigate if there has been a shift in treatment with tofacitinib, assessing real world patient data and entered in the Corrona registry between 2016 and 2020.

Official Title
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Comparative Effectiveness of Tumor Necrosis Factor (TNF) Inhibitors and Tofacitinib, Overall, by Line of Therapy and by Combination Therapy

Conditions
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Arthritis Rheumatoid

Intervention / Treatment
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* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RA patients in Corrona initiating tofacitinib or a TNF biologic (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) after 06 November 2012 (market approval of Tofacitinib) during follow-up in Corrona with no prior use of tofacitinib. Only the patient's first initiation after 06 November 2012 will be included in the analysis Have a 6 and / or 12-month follow-up visit (with +/- 2 month window) Have Clinical Disease Activity Index (CDAI) measures at baseline and at the follow-up visit Exclusion Criteria: Patients who have not failed methotrexate (MTX) or another csDMARD (ie 1st line initiators)
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 |
| --- | --- |
| Patients with Rheumatoid Arthritis (RA)<br> | Drug: Tofacitinib<br>* Patients who received Tofacitinib for RA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants achieving low disease activity at 6 months | 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 <=10) at Month 6 have been reported. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants achieving remission 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. | 6 months | 
| Number of participants achieving remission at month 12 | 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 12 have been reported. | 12 months | 
| Number of participants achieving low disease activity at 6 months | 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. Here, all participants who achieved remission (DAS28-ESR <=3.2) at Month 6 have been reported | 6 months | 
| Number of participants achieving low disease activity at 12 months | 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. Here, all participants who achieved remission (DAS28-ESR <=3.2) at Month 6 have been reported | 12 months | 
| Number of participants achieving low disease activity at month 12 | 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 <=10) at Month 12 have been reported. | 12 months | 
| 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. | 6 months | 
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Month 12 | 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. | 12 months | 
| 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) | 6 months | 
| 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). | 6 months | 
| 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). | 6 months | 
| 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) | 12 months | 
| 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). | 12 months | 
| 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). | 12 months | 
| 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. | 6 months | 
| Change From Baseline in Participant Fatigue Score at Month 12 | 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. | 12 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. | 6 months | 
| Change From Baseline in Participant Pain Score at Month 12 | 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. | 12 months | 
| 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. | 6 month | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 12 | 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. | 12 month | 
| 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. | 6 months | 
| Change From Baseline in Modified Health Assessment Questionnaire (mHAQ) Score at Month 12 | 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. | 12 months | 
| Number of Participants Achieving Minimally Clinically Important Difference (MCID) Improvement From Baseline up to 6 months | MCID improvement assessed based on HAQ. 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. MCID improvement defined by difference in HAQ from baseline (at time of tofacitinib initiation) to 6 month visit of at least 0.22 | 6 months | 
| Number of Participants Achieving Minimally Clinically Important Difference (MCID) Improvement From Baseline up to 12 months | MCID improvement assessed based on HAQ. 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. | 12 months | 
| Number of Participants with mild pain | 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. Participants who had a baseline pain score of >= 20 were evaluable for this outcome measure and number of participants who a pain score less than or equal to 20 at Month 6 were reported. | 6 months | 
| Number of Participants with mild pain | 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. Participants who had a baseline pain score of >= 20 were evaluable for this outcome measure and number of participants who a pain score less than or equal to 20 at Month 12 were reported. | 12 months | 
| Change from baseline in Participant morning stiffness | Participants were asked the following question to answer: If you have morning stiffness, how long does it take until you feel as limber as you will for the day? in hours and minutes. Higher scores indicated a worsening of conditions. Total hours were reported for all participants at 6 months who reported morning stiffness >0 at baseline | 6 months | 
| Change from baseline in Participant morning stiffness | Participants were asked the following question to answer: If you have morning stiffness, how long does it take until you feel as limber as you will for the day? in hours and minutes. Higher scores indicated a worsening of conditions. Total hours were reported for all participants at 12 months who reported morning stiffness >0 at baseline | 12 months |