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Observational Study
. 2024 Nov 1;63(11):3135-3145.
doi: 10.1093/rheumatology/keae269.

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

Jack Arnold  1   2 , Lucy M Carter  1   2 , Md Yuzaiful Md Yusof  1   2 , Katherine Dutton  1   2 , Zoe Wigston  1   2 , Shouvik Dass  1   2 , Samuel Wood  1   2 , Samuel Relton  3 , Edward M Vital  1   2
Affiliations
Observational Study

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

Jack Arnold et al. Rheumatology (Oxford). .

Abstract

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.

Keywords: SLE; Sjögren’s syndrome; arthritis; autoimmune diseases; myositis.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study schematic. pSS: primary SS; IM: idiopathic myositis; WPAI: Work Productivity and Activity impairment; NKT: NK T cell
Figure 2.
Figure 2.
PRO and biomarker data by diagnosis. pSS: primary SS; IM: idiopathic myositis; PBMC: peripheral blood mononuclear cell; VAS: visual analogue score; EMS: early morning stiffness; PCS: physical component score; MCS: mental component score; pSS: primary SS
Figure 3.
Figure 3.
Collated PCA plots: (A) diagnosis; (B) SLE with high total BILAG; (C) SLE with high MSK BILAG; (D) GMM-based stratification. GMM: Gaussian mixture modelling; pSS: primary SS; IM: idiopathic myositis; MSK: musculoskeletal
Figure 4.
Figure 4.
Sankey plot showing make-up of GMM high and low groups. GMM: Gaussian mixture modelling; pSS: primary SS; IM: idiopathic myositis
See this image and copyright information in PMC

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