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Objective: Extramusculoskeletal manifestations of spondyloarthritis (SpA) may precede the development of articular features. Patients seen in ophthalmology, dermatology, and gastroenterology clinics with uveitis, psoriasis, or inflammatory bowel disease (IBD) may have undiagnosed SpA. We set out to identify and evaluate screening tools for SpA in patients with psoriasis, uveitis, and IBD and determine factors that influence the performance of these instruments., Methods: This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and Web of Science were searched from inception to January 2022., Results: We identified 13 screening tools for psoriatic arthritis, 2 SpA screening tools for uveitis, and 3 SpA screening tools for IBD. All screening tools were patient-oriented questionnaires except for the Dublin Uveitis Evaluation Tool, a physician-applied algorithm. The questionnaires varied in length, scoring method, cutoff score, and spectrum of included SpA features. Average completion time was less than five minutes. Across the three patient populations, the sensitivities and specificities of these screening tools were comparable in the primary validation cohorts. Sensitivities and specificities were generally lower in secondary validation studies, with marked variability among cohorts., Conclusion: Our results highlight the heterogeneity and limitations of existing SpA screening tools. Although these tools show promise for use within a specific target population, none are generalizable to all patients with extramusculoskeletal manifestations at risk of SpA. Future studies should explore the utility of a generic patient-oriented SpA screening tool that can be applied to patients with psoriasis, uveitis, or IBD; is easy to use and comprehend; and captures all clinical domains of SpA., (© 2024 American College of Rheumatology.)

Objective: Patients with axial spondyloarthritis (axSpA) often experience significant delay between symptom onset and diagnosis for reasons that are incompletely understood. We investigated associations between demographic, medical, and socioeconomic factors and axSpA diagnostic delay., Methods: We identified patients meeting modified New York criteria for ankylosing spondylitis (AS) or 2009 Assessment of Spondyloarthritis International Society criteria for axSpA in the Mass General Brigham health care system between December 1990 and October 2021. We determined the duration of diagnostic delay, defined as the duration of back pain symptoms reported at diagnosis, as well as disease manifestations and specialty care prior to diagnosis from the electronic health record. We obtained each patient's Social Vulnerability Index (SVI) by mapping their address to the US Centers for Disease Control SVI Atlas. We examined associations among disease manifestations, SVI, and diagnostic delay using ordinal logistic regression., Results: Among 554 patients with axSpA who had a median diagnostic delay of 3.8 years (interquartile range 1.1-10), peripheral arthritis (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.93) and older age at symptom onset (OR 0.83, 95% CI 0.78-0.88 per five years) were associated with shorter delay. AS at diagnosis (OR 1.85, 95% CI 1.30-2.63), a history of uveitis prior to diagnosis (OR 2.77, 95% CI 1.73-4.52), and higher social vulnerability (defined as national SVI 80th to 99th percentiles; OR 1.99, 95% CI 1.06-3.84) were associated with longer diagnostic delay., Conclusion: Older age at back pain onset and peripheral arthritis were associated with shorter delay, whereas uveitis was associated with longer diagnostic delay. Patients with higher socioeconomic vulnerability had longer diagnostic delay independent of clinical factors., (© 2023 American College of Rheumatology.)

Purpose of Review: This review takes a look at the past, present, and future of SPARTAN, the Spondyloarthritis Research and Treatment Network, an organization of North American healthcare professionals dedicated to advancing research, education, and patient care in spondyloarthritis., Recent Findings: In 2022, SPARTAN completed the Classification of Axial SpondyloarthritiS Inception Cohort (CLASSIC) study, a collaboration with the Assessment in SpondyloArthritis International Society (ASAS). CLASSIC aimed to validate the 2009 ASAS classification criteria for axial spondyloarthritis. Other ongoing SPARTAN endeavors include the development of US referral recommendations for axial spondyloarthritis, an update of the 2019 ACR/SAA/SPARTAN treatment recommendations for axial spondyloarthritis and multiple educational initiatives. Twenty years after its inception, SPARTAN continues to grow and broaden its impact, guided by the SPARTAN vision of "a world free of spondyloarthritis through leadership in research and education.", (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To critically appraise study designs evaluating spondyloarthritis (SpA) phenotypes in patients with inflammatory bowel disease (IBD). A systematic literature review of PubMed, Ovid, Scopus, Cinahl, Medline, Web of Science, and Cochrane databases was performed. Articles published from January 2000 - March 2020 were included if they evaluated the prevalence/incidence of musculoskeletal disease in cohorts of IBD patients. Most of the 69 included studies were clinic based (54/69, 78%), single center (47/69, 68%) and cross-sectional (60/69, 87%). The median prevalence of axial and peripheral SpA in IBD was 5% (range 1 - 46%) and 16% (range 1 - 43%), respectively. In 38 studies that evaluated axial disease in prospectively enrolled patients, inflammatory back pain was analyzed in 53%. SpA classification criteria were used in 68% and imaging was performed in 76%. In 35 studies that evaluated peripheral disease in prospectively enrolled patients, SpA classification criteria were used in 46%. A physical exam was performed in 74%, and it was performed by a rheumatologist in 54% of studies with a physical exam. Sub-phenotypes of peripheral SpA (mono- or oligo-arthritis, polyarthritis, enthesitis, dactylitis) were variably reported. Seventy-four percent of studies did not mention whether osteoarthritis and fibromyalgia had been assessed or excluded. The spectrum of SpA phenotypes in IBD patients remains incompletely characterized. Future studies should focus on standardizing the variables collected in IBD-SpA cohorts and defining musculoskeletal phenotypes in IBD-SpA in order to better characterize this disease entity and advance the field for clinical and research purposes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated., Methods: We compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA., Findings: Male B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight., Conclusions: The phenotype of IL-23 induced disease in mice is controlled by genetic background and sex of the animals. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests that organ-specificity of IL-23 driven inflammation is genetically determined. The mechanisms behind the strain-specific differences and the sexual dimorphism observed in this study may be relevant for human spondyloarthritis and warrant further exploration., Competing Interests: The authors have declared that no competing interests exist.

Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: ["axSpA" OR "axial SpA" OR "axial spondyloarthritis" OR "ankylosing spondylitis"]) in combination with terms related to IBP ("inflammatory back pain" OR "IBP" OR "chronic back pain" OR "CBP" OR "lower back pain" OR "LBP"), diagnosis (["diagn∗" OR "classification"] AND ["criteria" OR "recommend∗" OR "guidelines"]), and referral ("refer∗"). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review encompasses a detailed history of spondyloarthritis (SpA) evolution as early as the 17th century, continues on to the current concept of SpA, and ends with current gaps in our understandings of SpA., Recent Findings: Until the early 1960s, ankylosing spondylitis and other SpA family members were considered to be variants of rheumatoid arthritis (RA). The formal medical community separated them from RA at that time, and shortly thereafter they were recognized to be inter-connected based on shared clinical, laboratory, and imaging features. The last two decades have witnessed the formal distinction between axial and peripheral SpA and the connections that exist between nonradiographic and radiographic axial SpA. Recent studies have revealed different microbial compositions among patients with SpA and healthy controls and also between HLA-B27 positive and negative healthy individuals., Summary: Further investigation of the roles of intestinal microbiome and physical force transduction toward SpA pathogenesis, strategies to improve delay in SpA diagnosis, biomarkers to better predict radiographic progression, and modification of current classification criteria to better address the axial and peripheral groups are gaps in our understandings that pose top priorities for SpA research.

Objectives: To develop classification algorithms that accurately identify axial SpA (axSpA) patients in electronic health records, and compare the performance of algorithms incorporating free-text data against approaches using only International Classification of Diseases (ICD) codes., Methods: An enriched cohort of 7853 eligible patients was created from electronic health records of two large hospitals using automated searches (⩾1 ICD codes combined with simple text searches). Key disease concepts from free-text data were extracted using NLP and combined with ICD codes to develop algorithms. We created both supervised regression-based algorithms-on a training set of 127 axSpA cases and 423 non-cases-and unsupervised algorithms to identify patients with high probability of having axSpA from the enriched cohort. Their performance was compared against classifications using ICD codes only., Results: NLP extracted four disease concepts of high predictive value: ankylosing spondylitis, sacroiliitis, HLA-B27 and spondylitis. The unsupervised algorithm, incorporating both the NLP concept and ICD code for AS, identified the greatest number of patients. By setting the probability threshold to attain 80% positive predictive value, it identified 1509 axSpA patients (mean age 53 years, 71% male). Sensitivity was 0.78, specificity 0.94 and area under the curve 0.93. The two supervised algorithms performed similarly but identified fewer patients. All three outperformed traditional approaches using ICD codes alone (area under the curve 0.80-0.87)., Conclusion: Algorithms incorporating free-text data can accurately identify axSpA patients in electronic health records. Large cohorts identified using these novel methods offer exciting opportunities for future clinical research., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Scientific breakthroughs have culminated in the development of the spondyloarthritis (SpA) concept as a family of rheumatic diseases, distinct from rheumatoid arthritis. The demonstration of inflammatory lesions in the sacroiliac joints and spine of patients with axial symptoms of SpA who lacked radiographic features of ankylosing spondylitis (AS) helped refine the SpA concept. Axial SpA includes patients with AS and patients with axial symptoms previously categorized as undifferentiated SpA. This review examines the sources of knowledge that inform axial SpA pathogenesis, highlighting current limitations, and a basic working model of axial SpA pathogenesis., Competing Interests: Disclosure Supported by research grants from the Arthritis National Research Foundation and the National Psoriasis Foundation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W)., Methods: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52., Results: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks., Conclusion: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab., Trial Registration Number: NCT02696785/NCT02696798., Competing Interests: Competing interests: MD has served as a consultant and received research grants from AbbVie, Eli Lilly and Company, Pfizer and UCB Pharma. JC-CW has served as a consultant and/or speaker and/or has received research grants from Abbott, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB Pharma. RL has served as a consultant and/or advisor and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Galapagos, Merck, Novartis, Pfizer and UCB Pharma. RL is the director of Rheumatology Consultancy BV, a company that was indirectly contracted by Eli Lilly and Company to perform read services for the COAST program. JS has served as a consultant and/or speaker for AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche and UCB Pharma. XB has served as a consultant and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma. FVdB has served as a consultant and/or speaker and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Sanofi and UCB Pharma. WPM has served as a consultant and/or received honoraria and/or research/educational grants from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, and is Chief Medical Officer of CARE Arthritis Limited. JE has served as a consultant and/or received research grants from AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. JAW has been a consultant and/or received research grants from AbbVie, Amgen, Celgene, Eli Lilly and Company, Novartis, Pfizer and UCB Pharma. AD has been a consultant and/or received research support from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith & Klein, Janssen, Novartis, Pfizer and UCB Pharma. DvdH has been a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma and is a Director of Imaging Rheumatology BV. TT has been a consultant and speaker for AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Pfizer and Takeda. XL, FZ, CCB, GG and HC are current employees and shareholders of Eli Lilly and Company. LSG has been a consultant and/or received research grants/support from AbbVie, Amgen, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States., Methods: We performed a cross-sectional study using electronic medical records from two academic hospitals in the United States. Data were extracted using automated searches (⩾3 ICD codes combined with text searches) and supplemented with manual chart review. Patients were categorized into AS or nr-axSpA according to classification criteria. Disease features, comorbidities (from a list of 39 chronic conditions) and history of bDMARD prescription were compared using descriptive statistics., Results: Among 965 patients identified, 775 (80%) were classified as having axSpA. The cohort was predominantly male (74%) with a mean age of 52.5 years (s.d. 16.8). AS patients were significantly older (54 vs 46 years), more frequently male (77% vs 64%) and had higher serum inflammatory markers than those with nr-axSpA (median CRP 3.4 vs 2.2 mg/dl). Half of all patients had at least one comorbidity. The mean number of comorbidities was 1.5 (s.d. 2.2) and similar between AS and nr-axSpA groups. A history of bDMARD-use was seen in 55% of patients with no difference between groups. The most commonly prescribed bDMARDs were adalimumab (31%) and etanercept (29%). Ever-prescriptions of individual bDMARDs were similar between AS and nr-axSpA., Conclusion: Despite age differences, nr-axSpA patients had similar comorbidity burdens as those with AS. Both groups received comparable bDMARD treatment in this United States clinic-based cohort., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ObjectiveTo provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).MethodsA core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework.ResultsIn patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS.ConclusionThese recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.