ANA-associated arthritis: clinical and biomarker characterization of a population for basket trials.

Autor:	Arnold J; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Carter LM; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Md Yusof MY; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Dutton K; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Wigston Z; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Dass S; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Wood S; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Relton S; Leeds Institute of Data Analytics, University of Leeds, Leeds, UK., Vital EM; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Nov 01; Vol. 63 (11), pp. 3135-3145.
DOI:	10.1093/rheumatology/keae269
Abstrakt:	Objectives: ANA-associated rheumatic and musculoskeletal (MSK) diseases (RMDs) [SLE, primary SS (pSS), scleroderma, inflammatory myositis, MCTD and UCTD] make up a disease spectrum with overlapping clinical and immunological features. MSK inflammation is common and impactful across ANA-associated RMDs. The objectives of this study were to evaluate MSK inflammation (ANA-associated arthritis) prevalence in a multidisease ANA-associated RMD study, assess its clinical impact across ANA-associated RMD diagnoses, propose new basket groupings of patients, and evaluate immunological profiles in legacy and new basket contexts. Methods: An observational study enrolled patients with ANA-associated RMDs. Demographic variables, comorbidities, therapies, disease activity instruments [BILAG, SLEDAI, the EULAR SS disease activity index (ESSDAI), physician visual analogue scale (VAS)], patient-reported outcomes [SF36, FACIT-Fatigue, EQ5D, ICECAP-A, Work Productivity and Activity impairment (WPAI), patient VAS] and the biomarker profile (six-gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian mixture modelling (GMM). The clinical and immune features of new and legacy clusters were compared. Results: Inflammatory MSK symptoms were prevalent across ANA-associated RMDs, in 213/294 patients. In ANA-associated arthritis patients, most variables did not differ between diagnoses, with the exception of the EQ5D-5L index and mobility domains (lower in MCTD/pSS, both P < 0.05). FM and OA prevalence were similar across diagnoses. Therapy use differed significantly, the use of biologics being greatest in SLE (P < 0.05). GMM yielded two multidisease clusters: High MSK disease activity (n = 89) and low MSK disease activity (n = 124). The high MSK disease activity cluster included all patients with active joint swelling, and they had significantly higher prednisolone usage, physician global assessment (PGA), Sm/RNP/SmRNP/chromatin positivity, Tetherin mean fluorescence intensity (MFI), and IFN Score-A activity, along with numerically lower FM and OA prevalence. Conclusion: We defined ANA-associated arthritis, a more clinically and immunologically homogeneous population than existing RMD populations for trials, and a more prevalent population for therapies in the clinic. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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