Lead Investigator: Dafne Capelusnik, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
Title of Proposal Research: Validating a Personalised Ankylosing Spondylitis Metrology Index
Vivli Data Request: 8576
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Radiographic axial spondylarthritis (r-axSpA), also known as Ankylosing Spondylitis, is a disease in which inflammation in the spine can lead to bony fusion between vertebrae and arthritis in the hip joints, leading to a temporary or permanent loss of mobility in these joints. With the aid of a tape measure and a simple goniometer (an instrument for the precise measurement of angles), clinicians started tracking these changes in mobility over the course of the disease by measuring in the neck, spine, and hips.
Since 1944, an index of these measurements was developed, The Bath Ankylosing Spondylitis Metrology Index (BASMI), and its formula has undergone minor modifications (from nominal scales to a continuous scale) being the BASMI Linear the last the version most commonly used in recent clinical trials due to its higher practicability in computer evaluations.
Over the past 15 years, the use of MRI rather than x-ray to achieve an earlier diagnosis has led to the introduction of a new and more inclusive term for the disease ‘axial spondylarthritis’ (axSpA), including patients diagnosed in an earlier stage. Although the BASMI is still widely used, some clinical trials that have focused on patients with early axSpA have often reported a lack of responsiveness of BASMI, suggesting that this outcome tool may no longer be appropriate in this group of patients. Indeed, the Assessment of SpondyloArthritis international Society (ASAS) has recently reviewed the core set for axSpA and determined that the BASMI should no longer be recommended as a core outcome domain for inclusion in all axSpA therapeutic studies. Among the reasons for this change are the floor effect, where patients score at the bottom of the scale, seen in patients with short disease duration, and poor sensitivity to change and a ceiling effect, where patients scope at the top of the scale.
At the time the BASMI was developed, it had not been tested on a group of normal individuals. When this was systematically studied in the MOBILITY study of healthy individuals, it was found that the BASMI was strongly influenced by factors such as height, age and gender. Another important observation in the MOBILITY study was that whilst the occiput to wall distance was zero in 95% of healthy individuals (as expected), not a single one had a normal Tragus to wall distance (TTW) score which had been a reliable measurement used prior to this. The MOBILITY study in the healthy population clearly showed that the BASMI Linear assigns inappropriately high/low readings for spinal mobility to a substantial proportion of people, particularly those who are shorter/taller than average and those patients who are older.
This means that the clinician’s assessment of the severity of mobility restriction can be quite inaccurate as they are unaware of the adjustments that need to be made. In addition, the formula for calculating the Tragus to wall scale in the BASMI Linear is clearly misleading and needs to be corrected. We therefore believe that an adjusted version of the BASMI Linear, taking age, height and gender into account would have better psychometric properties than the ones from the original BASMI Linear.
As a first step of this project, the Personalised Axial Spondylarthritis Metrology Index (PASMI) was developed. The PASMI allows, by adjusting each individual spinal mobility measure for age, height and gender, as appropriate, to deliver a more ‘truthful’ representation of spinal mobility for each individual. The PASMI also redefines the normal limit of the scale using the data from the healthy population and corrects the ‘false floor’ in the TTW score. The PASMI score has been designed to be more ‘truthful’ than BASMI for the individual, and hopefully this will also improve its psychometric properties in comparison to those of the BASMI and the individual spinal mobility measures. We further hypothesized that the TTW measurement will have a large floor effect in cohorts with early axSpA, so we will compare the psychometric properties in both instruments (PASMI and BASMI) stratified by duration of disease/symptoms.
Requested Studies:
A Phase 3, Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis
Data Contributor: AbbVie
Study ID: NCT00195819
Sponsor ID: M03-606
A Randomized, Double-blind Trial of the Efficacy of REMICADE (Infliximab) Compared With Placebo in Subjects With Ankylosing Spondylitis Receiving Standard Anti-inflammatory Drug Therapy
Data Contributor: Johnson & Johnson
Study ID: NCT00207701
Sponsor ID: CR004792
A Randomized, Double-Blind Study Evaluating the Safety and Efficacy of Etanercept and Sulphasalazine in Subjects With Ankylosing Spondylitis
Data Contributor: Pfizer Inc.
Study ID: NCT00247962
Sponsor ID: 0881A3-402
A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFα Monoclonal Antibody, Administered Intravenously, in Subjects With Active Ankylosing Spondylitis
Data Contributor: Johnson & Johnson
Study ID: NCT02186873
Sponsor ID: CR103795
A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFalpha MonoclonalAntibody, Administered Subcutaneously, in Subjects With Active Ankylosing Spondylitis
Data Contributor: Johnson & Johnson
Study ID: NCT00265083
Sponsor ID: CR006337
A Multicenter, Open-label (Part A) Followed by a Randomized, Double-blind, Parallel-group, Placebo Controlled Study (Part B) to Evaluate Maintenance of Remission in Subjects With Active Axial Spondyloarthritis (axSpA) Receiving Either Certolizumab Pegol 200 mg Q2W or 200 mg Q4W as Compared to Placebo
Data Contributor: UCB
Study ID: NCT02505542
Sponsor ID: AS0005
Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis
Data Contributor: UCB
Study ID: NCT01087762
Sponsor ID: AS001
A Multicenter, Randomized, Double-Blind, Active and Placebo-Controlled 16-Week Study Followed by Long-Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD-Naive Patients With Radiographic Axial Spondyloarthritis
Data Contributor: Lilly
Study ID: NCT02696785
Sponsor ID: 16178
A Multicenter, Randomized, Double-Blind, Placebo- Controlled 16-Week Study Followed by Long-Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in TNFi-Experienced Patients With Radiographic Axial Spondyloarthritis
Data Contributor: Lilly
Study ID: NCT02696798
Sponsor ID: 16179
A 52-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients With Nonradiographic Axial Spondyloarthritis
Data Contributor: Lilly
Study ID: NCT02757352
Sponsor ID: 16180
A Multicentre, 12 Week Double Blind Placebo Controlled Randomized Study Of Etanercept On A Background Nsaid In The Treatment Of Adult Subjects With Non Radiographic Axial Spondyloarthritis With A 92 Week Open Label Extension
Data Contributor: Pfizer Inc.
Study ID: NCT01258738
Sponsor ID: B1801031
A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Axial Spondyloarthritis
Data Contributor: AbbVie
Study ID: NCT00939003
Sponsor ID: M10-791
Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis (axSpA) Without X-Ray Evidence of Ankylosing Spondylitis (AS) and Objective Signs of Inflammation
Data Contributor: UCB
Study ID: NCT02552212
Sponsor ID: AS0006
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis
Data Contributor: AbbVie
Study ID: NCT03178487
Sponsor ID: M16-098
Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)
Data Contributor: Pfizer Inc.
Study ID: NCT03502616
Sponsor ID: NCT03502616