An Observational Study to Assess the Real-World Effectiveness of Upadacitinib in Adult Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. RA can reduce the ability to perform everyday tasks. This study will assess the clinical and patient-reported outcomes with upadacitinib in adult participants with moderate-to-severe RA in a real-world setting. Upadacitinib is an approved drug for the treatment of adults with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate. Adult participants with moderate-to-severe RA will be enrolled. Around 150 participants will be enrolled in the study in multiple sites in the United Kingdom. Participants will receive upadacitinib per their physician's usual prescription. Individual data will be collected for 6 months. No additional study-related tests will be conducted during the routine physician visits. Only data which are routinely collected during a regular visit will be utilized for this study.

Official Title
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Real World Clinical and Patient-Reported Outcomes of Patients With Moderate-to-Severe Rheumatoid Arthritis Initiating Upadacitinib in the United Kingdom: A Prospective, Observational Cohort Study

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) confirmed diagnosis of rheumatoid arthritis (RA). Moderate RA (defined by National Institute for Health and Care Excellence [NICE] as 28-joint Disease Activity Score [DAS28] C-reactive protein [CRP] >3.2 and ≤5.1) or severe RA (defined by NICE as DAS28 CRP >5.1) at the time of enrollment. Prescribed upadacitinib in line with marketing authorization. Decision to treat with upadacitinib has been made independently and prior to enrolment in the study. Able to read and understand English. Willing and able to participate in the collection of patient-reported data via mobile app. Exclusion Criteria: First dose of upadacitinib received prior to enrollment in the study (same day permitted) or more than 28 days after enrolment into the study. Previously received >4 biologic disease-modifying antirheumatic drugs (bDMARD) (1 switch to a biosimilar for non-clinical reasons is allowed for each bDMARD received) or any Janus kinase (JAK) inhibitor for the treatment of RA. In the opinion of the treating clinician, participant symptoms are predominately being driven by fibromyalgia or unrelated pain component instead of underlying inflammatory disease. Participation in any interventional clinical trial within the 3 months prior to initiation or at any point during the study observation period.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants treated with upadacitinib<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving 28-Joint Disease Activity Score (DAS28) C-reactive protein (CRP) Clinical Remission | The DAS28 CRP is a composite measure of a patient's level of disease activity at a given time. The score ranges from 0-9.4 with a higher score correlating to higher disease activity. Clinical remission is defined as a DAS28 CRP <2.6. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Moderate European League Against Rheumatism (EULAR) Response | The DAS28 CRP is a composite measure of a patient's level of disease activity at a given time. The score ranges from 0-9.4 with a higher score correlating to higher disease activity. A moderate EULAR response is defined as a DAS28 CRP >5.1 with a DAS28 CRP decrease >1.2 or DAS 28 CRP score >3.2 and ≤5.1 with DAS28 CRP decrease >0.6. | 6 Months | 
| Percentage of Participants Achieving DAS28 CRP Clinical Remission | The DAS28 CRP is a composite measure of a patient's level of disease activity at a given time. The score ranges from 0-9.4 with a higher score correlating to higher disease activity. Clinical remission is defined as a DAS28 CRP <2.6. | 3 Months | 
| Percentage of Participants Achieving DAS28 CRP Low Disease Activity | The DAS28 CRP is a composite measure of a patient's level of disease activity at a given time. The score ranges from 0-9.4 with a higher score correlating to higher disease activity. Low disease activity is defined as DAS28 CRP <=3.2. | 3 Months | 
| Percentage of Participants Achieving DAS28 CRP Low Disease Activity | The DAS28 CRP is a composite measure of a patient's level of disease activity at a given time. The score ranges from 0-9.4 with a higher score correlating to higher disease activity. Low disease activity is defined as DAS28 CRP <=3.2. | 6 Months | 
| Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Clinical Remission | The CDAI is a validated measure of RA disease activity. Scores on the CDAI range from 0 (lowest disease activity) to 76 (highest disease activity). Clinical remission is defined as CDAI <=2.8. | 3 Months | 
| Percentage of Participants Achieving CDAI Low Disease Activity | The CDAI is a validated measure of RA disease activity. Scores on the CDAI range from 0 (lowest disease activity) to 76 (highest disease activity). Low disease activity is defined as CDAI <=10. | 3 Months | 
| Percentage of Participants Achieving CDAI Clinical Remission | The CDAI is a validated measure of RA disease activity. Scores on the CDAI range from 0 (lowest disease activity) to 76 (highest disease activity). Clinical remission is defined as CDAI <=2.8. | 6 Months | 
| Percentage of Participants Achieving CDAI Low Disease Activity | The CDAI is a validated measure of RA disease activity. Scores on the CDAI range from 0 (lowest disease activity) to 76 (highest disease activity). Low disease activity is defined as CDAI <=10. | 6 Months | 
| Percentage of Participants Achieving Boolean Remission | Boolean remission is achieved when all of the following conditions are satisfied: tender joint count <=1, swollen joint count <=1, CRP <=1 mg/dL, and patient global assessment <=1 (on a 0-10 scale). | 3 Months | 
| Percentage of Participants Achieving Boolean Remission | Boolean remission is achieved when all of the following conditions are satisfied: tender joint count <=1, swollen joint count <=1, CRP <=1 mg/dL, and patient global assessment <=1 (on a 0-10 scale). | 6 Months | 
| Percentage of Participants Initiating Upadacitinib as Monotherapy | Percentage of participants initiating upadacitinib without conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). | Baseline | 
| Percentage of Participants Initiating Upadacitinib in Combination Therapy | Percentage of participants initiating upadacitinib in combination therapy with csDMARDs. | Baseline | 
| Time to Discontinuation of Upadacitinib | Time from initiation to discontinuation of upadacitinib. | Up to 6 Months | 
| Percentage of Participants Remaining on Treatment | Percentage of participants remaining on upadacitinib 6 months post initiation. | 6 Months | 
| Number of Other (Not Rheumatoid Arthritis [RA]-Related) Concomitant Medications Prescribed | Other (not RA-related) concomitant medications include statins and other non-RA-related concomitant medications. | Baseline | 
| Number of RA-Related Concomitant Medications Prescribed | RA-related concomitant medications include csDMARDS, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), other painkillers, and other RA-related concomitant medications. | Up to 6 Months | 
| Percentage of Participants Who Have Received any COVID-19 or Herpes Zoster Vaccination | Percentage of participants who have received any COVID-19 or Herpes Zoster vaccination and a summary of vaccination details. | Up to 6 Months | 
| Change from Baseline in Pain Visual Analogue Scale (VAS) | The patient's level of pain in the last 24 hours will be measured using a pain VAS. VAS scores range from 0 to 100 points with a higher score indicating more pain. | Up to 6 Months | 
| Change from Baseline in Fatigue VAS Score | A fatigue VAS will be used to assess the patient's level of fatigue on a weekly basis. VAS scores range from 0 to 100 points with a higher score indicating more fatigue. | Up to 6 Months | 
| Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score | The FACIT-Fatigue Scale measures an individual's level of fatigue during their usual daily activities over the past week. on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The score range for FACIT-Fatigue is between 0 and 52. A score of less than 30 indicates severe fatigue. The higher the score, the better the quality of life. | Up to 6 Months | 
| Change from Baseline in Patient Health Questionnaire-2 (PHQ-2) Score | The PHQ-2 screens for the presence of possible depression. The PHQ-2 inquires about the frequency of depressed mood and anhedonia over the past 2 weeks, scoring each component from 0 (not at all) to 3 (nearly every day). | Up to 6 Months | 
| Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | The HAQ-DI assesses physical function in RA. The HAQ-DI score is the average of the highest score in each of eight categories. The total score is between 0-3.0, in 0.125 increments. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment | Up to 6 Months | 
| Change from Baseline in EQ-5D-5L Score | The EQ-5D-5L comprises of five 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. In addition, a vertical VAS is used to assess patient's self-rated health status. The endpoints for the VAS are labelled 'the best health you can imagine' and 'the worst health you can imagine'. The recall period is one day. | Up to 6 Months | 
| Change from Baseline in Work Productivity and Activity Impairment Questionnaire-General Health (WPAI-GH) Score | The WPAI-GH measures the impact of health problems on absenteeism, presenteeism, overall work performance and non-work activities using a 0 to 10 VAS. | Up to 6 Months | 
| Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Pain VAS | The patient's level of pain in the last 24 hours will be measured using a pain VAS. VAS scores range from 0 to 100 points with a higher score indicating more pain. MCID is defined as at least a 10 point difference from baseline. | Up to 6 Months | 
| Percentage of Participants Achieving MCID in Fatigue VAS Score | A fatigue VAS will be used to assess the patient's level of fatigue on a weekly basis. VAS scores range from 0 to 100 points with a higher score indicating more fatigue. MCID is defined as a decrease of -1.12. | Up to 6 Months | 
| Percentage of Participants Achieving MCID in FACIT-Fatigue Score | The FACIT-Fatigue Scale measures an individual's level of fatigue during their usual daily activities over the past week. on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The score range for FACIT-Fatigue is between 0 and 52. A score of less than 30 indicates severe fatigue. The higher the score, the better the quality of life. MCID is defined as a 4-point increase. | Up to 6 Months | 
| Percentage of Participants Achieving MCID in PHQ-2 Score | The PHQ-2 screens for the presence of possible depression. The PHQ-2 inquires about the frequency of depressed mood and anhedonia over the past 2 weeks, scoring each component from 0 (not at all) to 3 (nearly every day). MCID is defined as achievement of a PHQ-2 score <=2 and absence of low mood. | Up to 6 Months | 
| Percentage of Participants Achieving MCID in HAQ-DI Score | The HAQ-DI assesses physical function in RA. The HAQ-DI score is the average of the highest score in each of eight categories. The total score is between 0-3.0, in 0.125 increments. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. MCID is defined as decrease of -0.22. | Up to 6 Months | 
| Time to Achieve MCID in FACIT-Fatigue Score | The FACIT-Fatigue Scale measures an individual's level of fatigue during their usual daily activities over the past week. on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The score range for FACIT-Fatigue is between 0 and 52. A score of less than 30 indicates severe fatigue. The higher the score, the better the quality of life. MCID is defined as a 4-point increase. | Up to 6 Months | 
| Time to Achieve MCID in Pain VAS | The patient's level of pain in the last 24 hours will be measured using a pain VAS. VAS scores range from 0 to 100 points with a higher score indicating more pain. MCID is defined as at least a 10 point difference from baseline. | Up to 6 Months | 
| Time to Achieve MCID in Fatigue VAS Score | A fatigue VAS will be used to assess the patient's level of fatigue on a weekly basis. VAS scores range from 0 to 100 points with a higher score indicating more fatigue. MCID is defined as a decrease of -1.12. | Up to 6 Months | 
| Time to Achieve MCID in PHQ-2 Score | The PHQ-2 screens for the presence of possible depression. The PHQ-2 inquires about the frequency of depressed mood and anhedonia over the past 2 weeks, scoring each component from 0 (not at all) to 3 (nearly every day). MCID is defined as achievement of a PHQ-2 score <=2 and absence of low mood. | Up to 6 Months | 
| Time to Achieve MCID in HAQ-DI Score | The HAQ-DI assesses physical function in RA. The HAQ-DI score is the average of the highest score in each of eight categories. The total score is between 0-3.0, in 0.125 increments. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. MCID is defined as decrease of -0.22. | Up to 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis (RA), Upadacitinib, RINVOQ