Prologue: Spondyloarthritis Unmet Research Needs Conference IV.

The Spondylitis Association of America (SAA) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) convened a conference on the campus of the National Institutes of Health (NIH) on September 28 and 29, 2023, to identify unmet needs in spondyloarthritis (SpA) research. The conference featured presentations by experts in areas of disease endotypes, pain, innovative imaging in SpA, health disparities in rheumatic diseases, and therapeutics. Members of the conference planning committee moderated the sessions and led the development of manuscripts summarizing recommendations to address unmet research needs.

Unmet Needs in Spondyloarthritis: Imaging in Axial Spondyloarthritis.

Imaging biomarkers in axial spondyloarthritis (axSpA) are currently the most specific biomarkers for the diagnosis of this condition. Despite advances in imaging, from plain radiographs-which detect only damage-to magnetic resonance imaging (MRI)-which identifies disease activity and structural change-there are still many challenges that remain. Imaging in sacroiliitis is characterized by active and structural changes.

The mSQUASH is a feasible and valid measurement tool to uniformly assess daily physical activity in patients with rheumatic diseases.

Background: The modified Short QUestionnaire to ASsess Health-enhancing physical activity (mSQUASH) was originally developed and validated in Dutch patients with axial spondyloarthritis (axSpA). To support world-wide distribution, applicability and comparability of measuring physical activity, our aim was to perform translation and cross-cultural adaptation of the mSQUASH into English, field testing in other rheumatic diseases and clinical validation in patients with axSpA.

Methods: The Dutch mSQUASH was translated into English according to forward-backward Beaton protocol.

A secukinumab dose-escalation study in patients with ankylosing spondylitis not achieving inactive disease after 16 weeks of treatment.

Objective: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16.

Methods: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.

Pregnancy Outcomes in Patients Treated with Upadacitinib: Analysis of Data from Clinical Trials and Postmarketing Reports.

Background And Objective: Upadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy.

The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis.

Background: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA.

Methods: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes.

Efficacy and Safety of Tofacitinib in Ankylosing Spondylitis by Baseline C-Reactive Protein Level: Post Hoc Analysis of Phase II and Phase III Clinical Trials.

Objective: This post hoc analysis assessed the effect of baseline C-reactive protein (CRP) on the efficacy and safety of tofacitinib (TOF) use in ankylosing spondylitis (AS), as well as patient-reported outcomes (PROs).

Methods: Phase II (ClinicalTrials.gov: NCT01786668) and phase III (ClinicalTrials.

Long-term clinical outcomes of certolizumab pegol treatment in non-radiographic axial spondyloarthritis stratified by baseline MRI and CRP status.

Objective: There is a paucity of data on long-term clinical responses in patients with non-radiographic axial spondyloarthritis (nr-axSpA) based on their baseline objective signs of inflammation such as MRI or C-reactive protein (CRP) levels. This study reports clinical outcomes up to 3 years of the C-axSpAnd trial, including safety follow-up extension (SFE) from Weeks 52 to 156, stratified by patients' baseline MRI and CRP status.

Methods: C-axSpAnd (NCT02552212) was a phase 3, multicentre study that evaluated certolizumab pegol (CZP) in patients with active nr-axSpA who had active sacroiliitis on MRI and/or elevated CRP.

Goodbye to the term 'ankylosing spondylitis', hello 'axial spondyloarthritis': time to embrace the ASAS-defined nomenclature.

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs.

Structural disease modification in axial spondyloarthritis.

"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone formation. Recent years have witnessed the effectiveness of treatments, including biologics and nonsteroidal anti-inflammatory drugs, in managing axSpA symptoms. Emerging evidence points toward their potential impact on slowing structural disease progression.

Multimorbidity phenotypes in ankylosing spondylitis and their association with disease activity and functional impairment: Data from the prospective study of outcomes in ankylosing spondylitis cohort.

Objectives: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS).

Methods: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+).

Tofacitinib Efficacy and Safety in Patients With Ankylosing Spondylitis by Prior Biologic Disease-Modifying Antirheumatic Drug Use: A Post Hoc Analysis.

Objective: To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease-modifying antirheumatic drug (bDMARD) use.

Methods: Data from a placebo-controlled, double-blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open-label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD-naive or tumor necrosis factor inhibitor [TNFi]-inadequate responder [IR], including bDMARD-experienced [non-IR]).

Achievement of higher thresholds of clinical responses and lower levels of disease activity is associated with improvements in workplace and household productivity in patients with axial spondyloarthritis.

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment.

Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA.

Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA.

Incidence Rate and Factors Associated With Fractures Among Medicare Beneficiaries With Ankylosing Spondylitis in the United States.

Objective: We evaluated the incidence rate and factors associated with fractures among adults with ankylosing spondylitis (AS).

Methods: We performed a retrospective cohort study with data from the Rheumatology Informatics System for Effectiveness registry linked to Medicare claims from 2016 to 2018. Patients were required to have two AS International Classification of Diseases codes 30 or more days apart and a subsequent Medicare claim.