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This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered. [ABSTRACT FROM AUTHOR]

Aim: To collect and summarize the available scientific evidence that evaluates the effects of physical exercise interventions on axial spondyloarthritis (axSpA)., Methods: A systematic review was conducted in accordance to the guidance of Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) to collect randomized controlled trials on the PubMed, Embase and Web of Science Core Collection databases. The search strategy included terms regarding physical exercise interventions targeted to axSpA participants and all of its variants in multiple combinations adapted to each one of the databases regarding its own special requirements. Several outcomes were defined: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), ASDAS (Ankylosing Spondylitis Disease Activity Score), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), the 36-item short form health survey (SF-36) and the Ankylosing Spondylitis Quality of Life questionnaire (ASQoL). Two independent researchers screened the titles and abstracts followed by full-text analysis when suitable, using EndnoteTM online. Selected articles, according to exclusion/inclusion criteria defined, were submitted to data extraction and bias assessment was performed for each study's outcomes using the Cochrane risk-of-bias tool for randomized trials., Results: A total of 2063 articles were identified through the electronic databases search. After removal of duplicates, 1435 were eligible for screening, of which 45 articles went through full text evaluation. Only 24 articles met the inclusion/exclusion criteria. Physical exercise contributes for a statistically significant improvement of BASDAI in 13 studies, BASFI in 10, BASMI in 6, ASDAS in 3, CRP in 2, ESR in 1, SF-36 in 2 and ASQoL in 3.No major adverse effects were reported and an overall benefit was noted with the implementation of physical exercise as a treatment modality for axSpA., Conclusion: Physical exercise seems to be an effective non-pharmacological therapy for axSpA, with positive effects in disease activity, physical function, and quality of life.

Objectives: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA)., Methods: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting., Results: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures., Conclusions: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA., Competing Interests: Competing interests: SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, and holds research grants from Pfizer and Lilly. AS has received speaker/consulting fees from UCB and Novartis. AO has nothing to declare. CW has nothing to declare. XB received consulting fees and research grants from AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. XB is an editorial board member of Annals of Rheumatic Diseases. RBML received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and UCB, and is director of Rheumatology Consultancy. FEVdB received consulting and/or speaker fees from AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. BB has nothing to declare. AB has nothing to declare. PC received consulting/speaker’s fees from Eli Lilly, Pfizer, AbbVie, Sanofi, Galapagos, Fresenius Kabi, Biogen, MSD, UCB and Novartis. AC received honoraria for lectures from AbbVie, Merck Sharp & Dohme and Novartis. FAvG received grants from Stichting ASAS, and consulting/speaker’s fees from Novartis, UCB, Pfizer, AbbVie, Eli Lilly, Bristol Myers Squibb and Celgene. PG received speaker’s fees from AbbVie. LG received consulting fees and research grants from AbbVie, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. JH has received speaker honoraria and participated in advisory boards for AbbVie, Lilly, Novartis and Janssen. MdH has nothing to declare. MH has received speaker’s fees from Novartis. UK has received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. CL-M has received speaker/consulting fees from UCB, Novartis, Janssen, Eli Lilly, MSD and AbbVie. PMM has received honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, and UCB, and is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). HM-O received grants from Janssen, Novartis and UCB, and consultancy/speaker's fees from AbbVie, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB. AM received research grants from UCB and consulting fees from AbbVie, Biogen, BMS, Eli Lilly, Gilead, Novartis, MSD, Pfizer and UCB. VN-C received grants/honoraria from AbbVie, Galapagos, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. MJN received grant from Novartis and consultancy/speaker's fees from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer. FMP-S received research grants from AbbVie, Janssen, and Novartis, and consulting fees from AbbVie, Bial, Biogen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Pharma Kern, UCB and Tecnimed. DP received research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, and consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, MoonLake, Novartis, Pfizer, Samsung Bioepis, and UCB, and speaker's fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. FP reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, Amgen, BMS, Celgene, Janssen, Hexal, MSD, Pfizer and Roche. MR received consulting fees from AbbVie, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma. MT has nothing to declare. SSZ has received consulting fees from UCB. NZ received research grants from AbbVie, Celgene, NewBridge and Pfizer; consulting fees from AbbVie, Eli Lilly, Pfizer, Gilead, Janssen, Novartis, NewBridge and Roche; and speaker's fees from AbbVie, Apotex, Eli Lilly, Janssen, Novartis, Pfizer, Pierre Fabre, Pharmaline, Roche and Sanofi-Aventis. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is director of Imaging Rheumatology., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)