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Introduction: Fatigue is a common and burdensome symptom in Psoriatic Arthritis (PsA), characterized by reduced physical and cognitive performance [1]. It has a multifactorial origin and arises from inflammatory processes, disease symptoms, sleep disturbances, or psychological comorbidities [2]. Besides these, recent data suggest a role of autoantibodies (abs) targeting G-protein coupled receptors (GPCR) in fatigue in Post-COVID syndrome [3]. Here, we aimed to characterize fatigue in PsA and to investigate its association with clinical parameters and GPCR abs.

Methods: Patients (n = 115) with active PsA were treated with either csDMARDs or biologics in accordance with GRAPPA recommendations. Over a 12-month period following treatment initiation, fatigue was assessed at seven time points using the FACIT-Fatigue questionnaire. In parallel, patients underwent in-depth clinical characterization. Levels of GPCR abs were measured by CellTrend GmbH (Germany).

Results: At baseline, patients showed a high disease activity, with a DAPSA score of 32.4 ± 23.6. In the FACIT-Fatigue questionnaire, 43.4% of patients reported severe fatigue, defined as a score < 30. Using Wilcoxon matched-pairs signed rank test, a significant reduction in fatigue scores was observed after 4 weeks (p=0.0202), 16 weeks (p=0.0118), 24 weeks (p=0.0168), 40 weeks (p=0.0008), and 52 weeks (p=0.0024) compared to baseline.

K-means clustering of FACIT-Fatigue scores at weeks 0, 2, 4, and 16 identified four clusters. One cluster, comprising 30.9% of patients, demonstrated an improvement in fatigue under immunosuppressive treatment. Comparison of therapeutics between clusters revealed no significant differences. Similarly, no significant differences were found between clusters regarding achievement of minimal disease activity criteria.

Multinomial regression analysis using GPCR abs as predictors of cluster assignment revealed a potential association with abs targeting angiotensin II type 1 receptor (p=0.029), muscarinic receptor 2 (p=0.043), adrenergic receptors α1 (p=0.010) and α2 (p=0.030), and protease-activated receptor 1 (p=0.029).

Conclusion: This study demonstrates that fatigue is highly prevalent and relevant in PsA. As only 30.9% of patients experienced a significant improvement in FACIT-Fatigue questionnaire with immunosuppressive treatment, the presented data suggest that fatigue is influenced by factors beyond inflammatory disease activity. These data support for the first time a role of GPCR Abs in fatigue in autoimmune diseases.

Disclosures: Nothing to declare.

References

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[2] Zielinski MR, Systrom DM, Rose NR. Fatigue, Sleep, and Autoimmune and Related Disorders. Front Immunol. 2019 Aug 6;10:1827. DOI: 10.3389/fimmu.2019.01827
[3] Sotzny F, Filgueiras IS, Kedor C, Freitag H, Wittke K, Bauer S, Sepúlveda N, Mathias da Fonseca DL, Baiocchi GC, Marques AHC, Kim M, Lange T, Plaça DR, Luebber F, Paulus FM, De Vito R, Jurisica I, Schulze-Forster K, Paul F, Bellmann-Strobl J, Rust R, Hoppmann U, Shoenfeld Y, Riemekasten G, Heidecke H, Cabral-Marques O, Scheibenbogen C. Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity. Front Immunol. 2022 Sep 27;13:981532. DOI: 10.3389/fimmu.2022.981532