A Study to Assess Disease Activity in Adult Participants With Axial Spondyloarthritis Who Receive Upadacitinib in a Real-world Setting

Study Overview
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Brief Summary
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Axial spondyloarthritis (axSpA) is an immune-mediated inflammatory disease primarily affecting the axial skeleton. The most frequent axSpA symptom is chronic, often inflammatory back pain that might be difficult to distinguish from other causes of chronic back pain. Many participants report persistent pain, including back pain, which impacts disease activity and and impairs quality of life while evoking typical disease burden such as sleep disturbance, social isolation, loss of productivity, as well as anxiety and depression. This study will assess the real-world effectiveness of upadacitinib on early and sustained disease control, and the association between pain and clinical/patient-reported outcomes in axSpA participants. Upadacitinib is being developed for the treatment of axSpA. Approximately 352 adult participants with active axSpA will be enrolled in Germany. Participants will receive oral upadacitinib tablets as prescribed by the physician prior to enrolling in this study in accordance with the terms of the local marketing authorization and professional and reimbursement guidelines with regards to dose, population and indication. The overall duration of the study is approximately 52 weeks. There may be a higher burden for participants in this study compared to usual standard of care due to study procedures. Participants will attend regular visits per routine clinical practice. The effect of the treatment will be checked by medical assessments, checking for side effects, and questionnaires.

Official Title
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Effectiveness of Upadacitinib in Patients With Axial Spondyloarthritis Suffering From Typical Disease Activity and Pain in a Real-World Setting

Conditions
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Axial Spondylarthritis (r-axSpA)

Intervention / Treatment
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* Drug: Upadacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of axSpA upon physician's judgement. Physician decision on participant treatment with upadacitinib must have been reached prior to and independently of recruitment in the study. Upadacitinib prescribed in accordance with the local label. Exclusion Criteria: Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). Participants with primary fibromyalgia (upon physician´s judgement) Participation in a clinical trial of an investigational drug, concurrently or within the last 30 days or five half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently enrolled in another clinical study. Participants who cannot be treated with upadacitinib according to the applicable local label.

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 Receiving Upadacitinib.<br> | Drug: Upadacitinib<br>* Tablet; Oral<br>* Other names: RINVOQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Ankylosing Spondylitis Disease Activity Score Low Disease Activity (ASDAS LDA [< 2.1]) | The ASDAS combines the following 5 disease activity variables: back pain (BASDAI Question 2 NRS score 0 - 10), peripheral pain/swelling (BASDAI Question 3 NRS score 0 - 10), duration of morning stiffness (BASDAI Question 6 NRS score 0 - 10), PtGA, and high-sensitivity c reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). Low disease is defined as an ASDAS < 2.1. | Week 24 | 
| Percentage of Participants Achieving ASDAS LDA (< 2.1) (i.e., Maintenance of Response) | The ASDAS combines the following 5 disease activity variables: back pain (BASDAI Question 2 NRS score 0 - 10), peripheral pain/swelling (BASDAI Question 3 NRS score 0 - 10), duration of morning stiffness (BASDAI Question 6 NRS score 0 - 10), PtGA, and high-sensitivity c reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). Low disease is defined as an ASDAS < 2.1. Maintenance of response is defined as those achieving LDA at Week 24 and Week 52. | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Assessment of Spondyloarthritis International Society Health Index (ASAS-HI) Score of 40 | The ASAS-HI has been developed to measure functioning and health in participants with SpA with the aim of defining and comparing the impact of the disease and health based on the biopsychosocial model of disease proposed by the International Classification of Functioning, Disability and Health (ICF). | Up to Week 52 | 
| Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score < 4 | The BASDAI is a commonly used measure to define disease activity levels in axSpA participants. The overall BASDAI score ranges from 0 to 10, with higher scores indicating greater disease activity. | Up to Week 52 | 
| Percentage of Participants Achieving ASDAS Inactive Disease (ID [< 1.3]) | The ASDAS combines the following 5 disease activity variables: back pain (BASDAI Question 2 NRS score 0 - 10), peripheral pain/swelling (BASDAI Question 3 NRS score 0 - 10), duration of morning stiffness (BASDAI Question 6 NRS score 0 - 10), PtGA, and high-sensitivity c reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). Inactive disease is defined as an ASDAS < 1.3. | Up to Week 52 | 
| Percentage of Participants Achieving ASDAS LDA (< 2.1) | The ASDAS is a composite index with proven validity and reliability to assess disease activity in axSpA participants, with LDA defined as a score < 2.1. | Up to Week 52 | 
| Change from Baseline in BASDAI | The BASDAI is a commonly used measure to define disease activity levels in axSpA participants. The overall BASDAI score ranges from 0 to 10, with higher scores indicating greater disease activity. | Up to Week 52 | 
| Change from Baseline in BASDAI at Week 1-4 | The BASDAI is a commonly used measure to define disease activity levels in axSpA participants. The overall BASDAI score ranges from 0 to 10, with higher scores indicating greater disease activity. | Week 4 | 
| Percentage of Participants with Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) for Participants with Baseline Enthesitis | The LEI is a clinical index used to assess enthesitis. It consists of 3 bilateral sites: Achilles tendon insertions, medial femoral condyles, and lateral epicondyles of the humerus. Tenderness at each site is quantified on a dichotomous basis: 0 means nontender and 1 means tender. | Up to Week 52 | 
| Percentage of Participants with Resolution of Dactylitis for Participants with Baseline Dactylitis | Presence of dactylitis (Yes/No) will be assessed by the physician. | Up to Week 52 | 
| Mean Change from Baseline in ASAS-HI | The ASAS-HI has been developed to measure functioning and health in patients with SpA with the aim of defining and comparing the impact of the disease and health based on the biopsychosocial model of disease proposed by the ICF. | Up to Week 52 | 
| Percentage of Participants with ASAS-HI <= 4 | The ASAS-HI has been developed to measure functioning and health in patients with SpA with the aim of defining and comparing the impact of the disease and health based on the biopsychosocial model of disease proposed by the ICF. | Up to Week 52 | 
| Mean Change from Baseline in Nocturnal Back Pain in Past 24 Hours | Pain will be measured using a 0 - 10 numerical rating scale (NRS) for nocturnal back pain (0 = no pain and 10 = most severe pain). | Up to Week 52 | 
| Mean Change from Baseline in Total Back Pain in Past 24 Hours | Pain will be measured using a 0 - 10 numerical rating scale (NRS) for nocturnal back pain (0 = no pain and 10 = most severe pain). | Up to Week 52 | 
| Mean Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | The BASFI is a validated PRO instrument for use in the axSpA participant population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to axSpA participants such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10 with higher scores indicating worse physical functioning in axSpA participants. | Up to Week 52 | 
| Mean Change from Baseline in Patient Health Questionnaire-4 (PHQ-4) | The 4-item PHQ-4 is an ultra-brief self-report questionnaire that consists of a 2-item depression scale (PHQ-2) and a 2-item anxiety scale (GAD-2). It is rated on a 4-point Likert-type scale. Its purpose is to allow for very brief and accurate measurement of depression and anxiety. | Up to Week 52 | 
| Percentage of Participants with Recurrence of Typical Extra-Musculoskeletal Manifestations (EMMs) | Participants with recurrence of typical extra-musculoskeletal manifestations (EMMs. | Up to Week 52 | 
| Percentage of Participants with new onset of typical EMMs | Participants with new onset of typical EMMs | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RINVOQ, Axial Spondylarthritis (axSpA), Upadacitinib