SPondyloarthritis EARly Definition (ASAS-SPEAR) Analysis of Symptom Duration Thresholds Using Pooled Data from Randomized Controlled Trials

Lead Investigator: Ramiro Sofia, Leiden University Medical Center
Title of Proposal Research: SPondyloarthritis EARly Definition (ASAS-SPEAR) Analysis of Symptom Duration Thresholds Using Pooled Data from Randomized Controlled Trials
Vivli Data Request: 7828
Funding Source: None
Potential Conflicts of Interest: Dr. Ramiro reports: Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB.
This is an independent project, under the auspices of the Assessment of Spondyloarthritis international Society (ASAS) society.
Disclosures will be managed by declaring them in any subsequent publications.
Dr. Navarro-Compán reports: Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis.
Disclosures will be managed by declaring conflicts in any subsequent publications.
Dr. Capelusnik reports: Speakers bureau: Jannsen, Roche, Grant/research support from: Novartis.
Disclosures will be managed by declaring conflicts in any subsequent publications.

Summary of the Proposed Research:
Spondyloarthritis (SpA) is a term used to describe a group of connective tissue diseases that cause prominent joint inflammation and affects 0.5%-2% of the population. It includes a wide spectrum of manifestations, including a presentation with predominantly axial manifestations (i.e. pain and swelling in the spine and the joints that connect the bottom of the spine to the pelvis), namely axial spondyloarthritis (axSpA), and with predominantly with peripheral manifestations, peripheral spondyloarthritis (pSpA). As a result of significant advances in the field of SpA, researchers started using the term ‘early SpA‘ to refer to the first phase of the disease. Nevertheless, no consensual definition has been established. In this respect, the Assessment of SpondyloArthritis international Society (ASAS) identified the need to establish a standardized definition for the term ‘early SpA’ in a research setting, since it had been widely used with many arbitrary definitions. Hence, the ASAS-SPEAR (SPondyloarthritis EARly definition) project aims at proposing a consensus definition of ‘early SpA’ to be employed in research. As a first step of this project, a systematic literature review (SLR) was conducted. This review had as objectives: 1) to identify all possible definitions used in the literature to define ‘early SpA’, including ‘early axSpA’ and ‘early pSpA’; 2) to summarize the evidence on the relationship between symptom/disease duration or the presence of radiographic damage and clinical treatment response in patients with axSpA. Two abstracts summarizing the results of the systematic literature review (SLR) will be presented at EULAR 2022 Congress. In addition, a full manuscript has been submitted for publication, another is in preparation.
The main conclusions of the SLR were that there is substantial heterogeneity in the definitions of ‘early SpA’ in the current literature, and that evidence on whether the duration of symptoms is related with different treatment outcomes is scarce and mostly inconclusive. Of note, when early was defined by disease duration or radiographic damage, no association with clinical treatment response was found. The results of this SLR were discussed among all ASAS members in the 2022 ASAS annual meeting. A voting took place, in which there was a consensus to pursue a definition of ‘early axSpA’. Additionally, the group voted this definition to be based on symptom duration. Currently, a Delphi survey among ASAS members is being conducted to decide on the details of this definition, as for example the final cut-off of this symptom duration (e.g. less than 2 years).
To inform the final decision on the ‘early axSpA’ definition, one of the steps of the ASAS-SPEAR project is to conduct analyses to assess treatment outcomes according to the different thresholds of symptom duration in patients included in randomized controlled trials (RCT). In this sense, it is relevant to know whether patients who are treated earlier or later in the course of their disease (with a definition based on symptom duration) have different outcomes or response to treatment. This information is not readily available for most of the conducted trials as it is not part of the regulatory requirements. Relying on an SLR with published data only is subject to publication bias. We therefore want to systematically obtain data through the sponsors or authors from eligible trials. The latter are identified through the SLRs conducted in the context of the ASAS-EULAR recommendations for the management of axSpA (previously published SLRs and also the recent SLR performed as the basis of the ongoing, 2022 update of the recommendations).

Requested Studies:
A Multicenter, Long-Term Extension Study of 104 Weeks, Including a Double-Blind, Placebo-Controlled 40-Week Randomized Withdrawal-Retreatment Period, to Evaluate the Maintenance of Treatment Effect of Ixekizumab (LY2439821) in Patients With Axial Spondyloarthritis
Data Contributor: Lilly
Study ID: NCT03129100
Sponsor ID: 16181

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 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 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 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
Study ID: NCT01258738
Sponsor ID: B1801031

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 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

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 Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Golimumab in the Treatment of Chinese Subjects With Ankylosing Spondylitis
Data Contributor: Johnson & Johnson
Study ID: NCT01248793
Sponsor ID: CR015916

A Phase 3, Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Study of Adalimumab in Adult Chinese Subjects With Active Ankylosing Spondylitis
Data Contributor: AbbVie
Study ID: NCT01114880
Sponsor ID: M11-991

Multicenter, Double-Blind, Parallel, Placebo-Controlled, Randomised Phase 3 Study of Etanercept in the Treatment of Patients With Ankylosing Spondylitis: 12-Week Final Data
Data Contributor: Pfizer
Study ID: NCT00421915
Sponsor ID: 0881A3-311

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 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 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 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: NCT00085644
Sponsor ID: M03-607

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, 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

Etanercept Withdrawal And Retreament Study In Subjects With Nr-ax SpA (RE-EMBARK)
Data Contributor: Pfizer
Study ID: NCT02509026

A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
Data Contributor: AbbVie
Study ID: NCT01808118