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

• ClinicalTrials.gov Identifier: NCT04721821
• Recruitment Status: Completed
• First Posted: January 25, 2021
• Last Update Posted: December 13, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Arthritis Rheumatoid	Drug: Tofacitinib

Study Design

• Study Type: Observational
• Actual Enrollment: 1 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Comparative Effectiveness of Tumor Necrosis Factor (TNF) Inhibitors and Tofacitinib, Overall, by Line of Therapy and by Combination Therapy
• Actual Study Start Date: January 22, 2021
• Actual Primary Completion Date: November 29, 2021
• Actual Study Completion Date: November 29, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Patients with Rheumatoid Arthritis (RA)	Drug: Tofacitinib; Patients who received Tofacitinib for RA

Outcome Measures

Primary Outcome Measures :

1. Number of participants achieving low disease activity at 6 months [ Time Frame: 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 <=10) at Month 6 have been reported.

Secondary Outcome Measures :

1. Number of participants achieving remission at month 6 [ Time Frame: 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 <=2.8) at Month 6 have been reported.
2. Number of participants achieving remission at month 12 [ Time Frame: 12 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 <=2.8) at Month 12 have been reported.
3. Number of participants achieving low disease activity at 6 months [ Time Frame: 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
4. Number of participants achieving low disease activity at 12 months [ Time Frame: 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
5. Number of participants achieving low disease activity at month 12 [ Time Frame: 12 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 12 have been reported.
6. Change From Baseline in Clinical Disease Activity Index (CDAI) at Month 6 [ Time Frame: 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.
7. Change From Baseline in Clinical Disease Activity Index (CDAI) at Month 12 [ Time Frame: 12 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.
8. Number of Participants Achieving Modified American College of Rheumatology 20% (mACR20) Response [ Time Frame: 6 months ]
   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)
9. Number of Participants Achieving Modified American College of Rheumatology 50% (mACR50) Response [ Time Frame: 6 months ]
   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).
10. Number of Participants Achieving Modified American College of Rheumatology 70% (mACR70) Response [ Time Frame: 6 months ]
    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).
11. Number of Participants Achieving Modified American College of Rheumatology 20% (mACR20) Response [ Time Frame: 12 months ]
    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. Number of Participants Achieving Modified American College of Rheumatology 50% (mACR50) Response [ Time Frame: 12 months ]
    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).
13. Number of Participants Achieving Modified American College of Rheumatology 70% (mACR70) Response [ Time Frame: 12 months ]
    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).
14. Change From Baseline in Participant Fatigue Score at Month 6 [ Time Frame: 6 months ]
    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.
15. Change From Baseline in Participant Fatigue Score at Month 12 [ Time Frame: 12 months ]
    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.
16. Change From Baseline in Participant Pain Score at Month 6 [ Time Frame: 6 months ]
    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.
17. Change From Baseline in Participant Pain Score at Month 12 [ Time Frame: 12 months ]
    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.
18. Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 6 [ Time Frame: 6 month ]
    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.
19. Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Month 12 [ Time Frame: 12 month ]
    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.
20. Change From Baseline in Modified Health Assessment Questionnaire (mHAQ) Score at Month 6 [ Time Frame: 6 months ]
    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.
21. Change From Baseline in Modified Health Assessment Questionnaire (mHAQ) Score at Month 12 [ Time Frame: 12 months ]
    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.
22. Number of Participants Achieving Minimally Clinically Important Difference (MCID) Improvement From Baseline up to 6 months [ Time Frame: 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
23. Number of Participants Achieving Minimally Clinically Important Difference (MCID) Improvement From Baseline up to 12 months [ Time Frame: 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.
24. Number of Participants with mild pain [ Time Frame: 6 months ]
    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.
25. Number of Participants with mild pain [ Time Frame: 12 months ]
    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.
26. Change from baseline in Participant morning stiffness [ Time Frame: 6 months ]
    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
27. Change from baseline in Participant morning stiffness [ Time Frame: 12 months ]
    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

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Data will be collected from the Corrona RA Registry. The Corrona RA Registry is a prospective, multicenter, observational disease-based registry.

Criteria

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)

Contacts and Locations

Locations

United States, New York

Pfizer

New York, New York, United States, 10017

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04721821
• Other Study ID Numbers: A3921389
• First Posted: January 25, 2021
• Last Update Posted: December 13, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Additional relevant MeSH terms:

Arthritis, Rheumatoid; Necrosis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Pathologic Processes; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Tofacitinib; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action