Patient-Reported Outcomes In Rheumatoid Arthritis Patients Treated With Tofacitinib Or Biological Disease-Modifying Antirheumatic Drugs (DMARDs) In Real Life Conditions

Study Overview
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Brief Summary
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This study is aimed to describe the outcomes related to physical activity, activity of disease, quality of life, work productivity and safety in Latin-American patients with Rheumatoid Arthritis (RA) treated with tofacitinib or biological DMARDs after failure to respond to conventional DMARDs in real-life conditions. This will be a non-interventional, hybrid study (prospective and retrospective data collection) comparing tofacitinib to biologic DMARD treatments in patients with RA after failure of conventional DMARDs. The population will be composed by adult patients over 18 years of age diagnosed with RA and who have been prescribed tofacitinib or any biological DMARDs.

Official Title
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PATIENT-REPORTED OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB OR BIOLOGICAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) IN REAL LIFE CONDITIONS

Conditions
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Arthritis, Rheumatoid

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age at the time of recruitment Patient diagnosed with moderate to severe RA ≥ 6 months before enrollment Patients who have had an inadequate response to the continuous use of methotrexate or combination of conventional DMARDs for at least 12 weeks before the study without dose change within the last 8 weeks before enrollment in the study Patients with no biological DMARDs use in patient history. Patients prescribed with tofacitinib or biological DMARDs in the last two weeks at doses established in ACR guidelines published in 2015 and following medical criteria. Acceptance for patients to participate in the study and signing of the informed consent. Exclusion Criteria: Patients who do not have the ability to answer the questionnaires by themselves or who have any kind of mental disorder that may affect their answers. Patients diagnosed with autoimmune rheumatic diseases other than RA and Sjogren's syndrome. Patients treated with biological DMARDs in monotherapy. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks or 5 half-lives (whichever is longer) after discontinuation of the investigational compound before the current study begins and/or during study participation. Patients with any current malignancy or a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Patients with lymphoproliferative disorders (e.g., Epstein Barr Virus (EBV) related lymphoproliferative disorder), a history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.

Ages Eligible for Study
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Minimum Age: 18 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Month 6 | Disease activity was assessed using RAPID3, which was based on participant-reported multi-dimensional health assessment questionnaire (MDHAQ). RAPID3 included 3 core data set measures of physical function, pain, and patient global estimate. Physical function=mean of scores from 10 individual questions on activities of daily living (each question scored from '0'=no difficulty to '3'=much difficulty), scores were transformed to give a total score=0 to 10, higher scores=greater difficulty. Pain and global estimate of health measured on Likert scale from '0'=no pain/feeling very well to '10'=pain as bad as it could be/ feeling very poorly, higher scores=greater difficulty/ worsening of condition. RAPID3 composite score: mean of physical function, pain, and global assessment scores, ranging from 0 to 10, higher values=greater disease activity. Data has been provided in terms of adjusted (consider impact of co-variables) and unadjusted mean (does not consider co-variables impact). | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adapted Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Month 6 | Functional status of participants was assessed using adapted HAQ-DI. Adapted HAQ-DI is a participant-reported questionnaire for the assessment of ability to perform tasks in 8 categories of daily living activities due to rheumatoid arthritis: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point Likert scale from 0 to 3, where 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by total 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. Data has been provided in terms of adjusted (consider impact of co-variables) and unadjusted mean (does not consider co-variables impact). | Month 6 | 
| Change From Baseline in Adapted Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Month 6 | Functional status of participants was assessed using adapted HAQ-DI. Adapted HAQ-DI is a participant-reported questionnaire for the assessment of ability to perform tasks in 8 categories of daily living activities due to rheumatoid arthritis: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point Likert scale from 0 to 3, where 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by total 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. Data has been provided in terms of adjusted (consider impact of co-variable) and unadjusted mean (does not consider co-variable impact). | Baseline, Month 6 | 
| European Quality of Life- 5 Dimension-3 Levels (EQ-5D-3L) Index Score at Month 6 | EQ-5D-3L is a standardized, participant-administered measure of self-reported health outcomes. It consists of two parts: EQ-5D index score (Part I) and the EQ-VAS (Part II). For Part I, i.e. EQ-5D-3L index score, participants rated their current health state on 5 single-item dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with each dimension having three levels of measure: 1= no problems, 2= some problems and 3= extreme problems. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total index score range of 0 to 1.00; higher scores indicating a better health state. Data has been provided in terms of adjusted (consider impact of co-variables) and unadjusted mean (does not consider co-variables impact). | Month 6 | 
| Change From Baseline in European Quality of Life- 5 Dimension-3 Levels (EQ-5D-3L) Index Score at Month 6 | EQ-5D-3L is a standardized, participant-administered measure of self-reported health outcomes. It consists of two parts: EQ-5D index score (Part I) and the EQ-VAS (Part II). For Part I, i.e. EQ-5D-3L index score, participants rated their current health state on 5 single-item dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with each dimension having three levels of function:. 1=no problems, 2=some problems and 3=extreme problems. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total index score range of 0 to 1.00; higher scores indicating a better health state. Data has been provided in terms of adjusted (consider impact of co-variables) and unadjusted mean (does not consider co-variables impact). | Baseline, Month 6 | 
| Work Productivity and Activity Impairment Questionnaire for Rheumatoid Arthritis (WPAI:RA) Scores at Month 6 | WPAI-RA: 6-questions participant rated questionnaire that measures effect of participant's RA on general health and symptom severity on work productivity and regular activities. Consisted of 6 questions, a binary question on current employment, 3 questions on hours of work and work-loss, and 2 questions based on 0-10 point scale to judge how RA affected productivity at work and outside of work (0 = no effect on work and 10 = completely prevented from working). It yielded four sub-scores: percent work time missed due to health (absenteeism), percent impairment while working (presenteeism), percent overall work impairment due to health (work productivity loss) and percent activity impairment due to health (daily activity impairment/loss). Sub-scores were expressed as an impairment percentage range from 0 to 100, where 0 = no impairment, 100 = completely impaired, higher scores=greater impairment and less productivity. Data has been provided in terms of adjusted and unadjusted mean. | Month 6 | 
| Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Rheumatoid Arthritis (WPAI:RA) Scores at Month 6 | WPAI-RA: 6-questions participant rated questionnaire that measures effect of participant's RA on general health and symptom severity on work productivity and regular activities. Consisted of 6 questions, a binary question on current employment, 3 questions on hours of work and work-loss, and 2 questions based on 0-10 point scale to judge how RA affected productivity at work and outside of work (0 = no effect on work and 10 = completely prevented from working). It yielded four sub-scores: percent work time missed due to health (absenteeism), percent impairment while working (presenteeism), percent overall work impairment due to health (work productivity loss) and percent activity impairment due to health (daily activity impairment/loss). Sub-scores were expressed as an impairment percentage range from 0 to 100, where 0 = no impairment, 100 = completely impaired, higher numbers=greater impairment and less productivity. Data has been provided in terms of adjusted and unadjusted mean. | Baseline, Month 6 | 
| Disease Activity Score Based on 28-joints Count (DAS28) at Month 6 | DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, erythrocyte sedimentation rate (ESR) (measured in millimeters per hour [mm/hour]) and patient's global assessment of disease activity according to 100-millimeter (mm) Visual Analog Scale (VAS) (scores ranging 0 [very well] to 100 mm [extremely bad], higher scores=worsening of condition). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 scores ranged from 0 to 10; higher scores indicated greater affectation due to disease activity. Data has been provided in terms of adjusted and unadjusted mean. | Month 6 | 
| Change From Baseline in Disease Activity Score Based on 28-joints Count (DAS28) at Month 6 | DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, erythrocyte sedimentation rate (ESR) (measured in millimeters per hour [mm/hour]) and patient's global assessment of disease activity according to 100-millimeter (mm) Visual Analog Scale (VAS) (scores ranging 0 [very well] to 100 mm [extremely bad], higher scores=worsening of condition). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 scores ranged from 0 to 10; higher scores indicated greater affectation due to disease activity. Data has been provided in terms of adjusted and unadjusted mean. | Baseline, Month 6 | 
| Number of Participants With Serious Adverse Event (SAE) and Non-serious Adverse Events (AEs) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included both serious and non-serious adverse event. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Baseline up to Month 6 | 
| Number of Participants With Serious Infections | Serious infection defined as any infection that requires hospitalization. | Baseline up to Month 6 | 
| Number of Participants Who Withdrew From Study Due to Adverse Events And Due to All Causes | Here, number of participants who withdrew from study due to AEs and due to all causes (withdrawals due to AEs, lost to follow up and unspecified reasons) have been described. | Baseline up to Month 6 |