An Observational Study of Infliximab in Participants Suffering From Ankylosing Spondylitis With Hip Involvement

Study Overview
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Brief Summary
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The purpose of this observational (a study that follows participants forward in time) study is to compare the functional improvement of hip joint using Harris hip score between 2 treatment groups (infliximab and conventional therapy) at Week 30 in ankylosing spondylitis (an autoimmune disease causing chronic inflammation at tendon ends and ligament attachment points) participants with hip involvement.

Detailed Description
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This is a multi-center (when more than 1 hospital or medical school team work on a medical research study), observational study to compare the effectiveness of infliximab with conventional therapies in ankylosing spondylitis participants with hip joint involvement. The study will be conducted in 3 parts: a 14-day screening, a 30-week first follow-up (Follow-up 1), and an additional 22-week follow-up (Follow-up 2) up to Week 52. Participants will be assigned to two groups based on the current treatments they are receiving: cohort 1 participants receiving infliximab with or without combination of disease modifying drugs (DMARDs-such as Sulfasalazine, Methotrexate and Thalidomide) and/or non-steroidal anti-inflammatory drugs (NSAIDs) and in cohort 2 who are receiving DMARDs and/or NSAIDs for treatment of pain will be observed. Participants will primarily be assessed for change in harris hip score. Participants' safety will be monitored throughout the study.

Official Title
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A Multicenter and Observational Study to Assess the Effectiveness of Infliximab Comparing With Conventional Therapy in Ankylosing Spondylitis Subjects With Hip Involvement

Conditions
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Spondylitis, Ankylosing

Intervention / Treatment
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* Drug: Infliximab
* Drug: NSAIDs
* Drug: DMARDs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with ankylosing spondylitis (AS) (according to the modified New York Criteria for AS) at least 3 months prior to the Day 1 in the Follow-up I phase with symptoms of active disease atScreening/Baseline Hip pain and duration of hip symptom less than 2 years Harris hip score less than (<) 70 Hip involvement proven by Magnetic resonance imaging (MRI) Being treated with infliximab and conventional therapy for 2 weeks to 6 months Exclusion Criteria: Participant has a history of hip joint disability which was considered irreversible Participant has a history of hip joint replacement Participant has a history of treatment with biologics other than infliximab less than 6 months prior to study entry

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 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 |
| --- | --- |
| Cohort 1: Infliximab and/or NSAIDs and DMRADs<br>Participants receiving intravenous infusion of infliximab with or without non-steroidal anti-inflammatory drugs (NSAIDs: aspirin, ibuprofen and naproxen) and Disease-modifying anti-rheumatic drugs (DMRADs: methotrexate (MTX), sulfasalazine, and thalidomide) will be observed. | Drug: Infliximab<br>* This is an observational study. Participants receiving intravenous infusion of infliximab will be observed.<br>Drug: NSAIDs<br>* This is an observational study. Participants receiving aspirin, ibuprofen and naproxen as NSAIDs will be observed.<br>Drug: DMARDs<br>* This is an observational study. Participants receiving methotrexate (MTX), sulfasalazine, and thalidomide as DMRADs will be observed.<br>|
| Cohort 2: NSAIDs and DMARDs<br>Participants receiving NSAIDs (aspirin, ibuprofen and naproxen) and DMARDs (MTX, sulfasalazine, and thalidomide) will be observed. | Drug: NSAIDs<br>* This is an observational study. Participants receiving aspirin, ibuprofen and naproxen as NSAIDs will be observed.<br>Drug: DMARDs<br>* This is an observational study. Participants receiving methotrexate (MTX), sulfasalazine, and thalidomide as DMRADs will be observed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Harris Hip Score at Week 30 | Harris hip score, a physician-assessed scoring method consisting of 10 items: pain, limp, support, distance walked, sitting, enter public transportation, stairs, put on shoes and socks, absence of deformity and range of motion. The scoring system covers domains like pain, function, absence of deformity and range of motion. The total Harris hip score has a maximum of 100 points with a higher score indicating a better hip function: Excellent (90-100), Good (80-89), Fair (70-79) and Poor (<70). | Baseline and Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Bath Ankylosing Spondylitis Disease Activities Index (BASDAI) Score at Week 30 and 52 | The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10cm visual analog scale (VAS), with 1 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness will be added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. | Baseline, Week 30 and 52 | 
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score at Week 30 and 52 | The BASFI is composed with 10 questions to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. Higher BASFI score indicates more severe functional limitations of the participant due to AS. | Baseline, Week 30 and 52 | 
| Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Score at Week 30 and 52 | The BASMI is an accurate and reproducible metrology index developed to assess the clinical changes in spinal movements of AS participants. This index consists of 5 clinical measurements, including lumber side flexion, tragus to wall, lumbar flexion (modified Schober's), intermalleoar distance and cervical rotation. The potential scores for each measurement are 0, 1, and 2, indicating a disease severity of mild, moderate and severe, respectively. A higher BASMI score indicates a more severe movement limitation due to AS. | Baseline, Week 30 and 52 | 
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 30 and 52 | The ASDAS is composite score based on the calculation of 5 disease activities: 4 are participant's reported outcomes (back pain, duration of morning stiffness, participant global and peripheral pain/swelling) and one serologic inflammation marker (creatinine reactive protein - CRP). The score is the sum of the 5 items with different specified weights, with a minimum of 0 and no upper limit. Thus this index can reflect both long term disease activity and acute phase status. There are 3 cut-offs in score to show: a) the 4 states of disease activity: inactive disease (<1.3), moderate disease activity (1.3-2.1), high disease activity (2.1-3.5) and very high disease activity (>3.5). b) effectiveness of the treatment, two validated cut-offs were developed: a change of 1.1-2.0 (clinically important improvement) and a change >2.0 (major improvement). | Baseline, Week 30 and 52 | 
| Change From Baseline in Harris Hip Score at Week 14 and 52 | Harris hip score, a physician-assessed scoring method consisting of 10 items: pain, limp, support, distance walked, sitting, enter public transportation, stairs, put on shoes and socks, absence of deformity and range of motion. The scoring system covers domains like pain, function, absence of deformity and range of motion. The total Harris hip score has a maximum of 100 points with a higher score indicating a better hip function: Excellent (90-100), Good (80-89), Fair (70-79) and Poor (<70). | Baseline, Week 14 and 52 | 
| Assessment of Improvement in Hip Joint | Radiological improvements of hip joint will be assessed using magnetic resonance imaging (MRI) and X-ray examinations. | Baseline, Week 30 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infliximab, Spondylitis, Ankylosing, Non-steroidal anti-inflammatory drugs, Disease-modifying anti-rheumatic drugs