POS0871 ANTI-CD74 AUTOANTIBODIES IN AXIAL SPONDYLOARTHRITIS AS BIOMARKERS FOR DISEASE ACTIVITY BUT NOT FOR EFFECTIVENESS OF TUMOUR NECROSIS FACTOR INHIBITOR TREATMENT: DATA FROM THE SWISS CLINICAL QUALITY MANAGEMENT IN RHEUMATIC DISEASES COHORT

<h2>Abstract</h2><h3>Background:</h3> CD74 is the human leucocyte class II gamma chain and the receptor of macrophage migration inhibitory factor, which is potentially involved in the pathogenesis of axial spondyloarthritis (axSpA). Anti-CD74 antibodies have been proposed as a diagnostic biomarker in axSpA and previous studies showed association with spinal damage. <h3>Objectives:</h3> The aims of this study were to evaluate the association of anti-CD74 Immunoglobulin A (IgA) with disease activity parameters (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], C-reactive protein [CRP]) in axSpA and to assess their predictive value for the effectiveness of treatment with tumour necrosis factor inhibitors (TNFi), using treatment retention as a surrogate outcome. <h3>Methods:</h3> Patients diagnosed with axSpA in the Swiss Clinical Quality Management registry with available biosamples were included. Anti-CD74 IgA were measured with SpADetect ELISA of Aesku.Diagnostics. We used a cut-off of 15 U/ml to define elevated anti-CD74 IgA, based on a study comparing patients with axSpA and fibromyalgia [1]. Associations of disease characteristics with anti-CD74 IgA elevation were evaluated using multivariable logistic regression models. For disease activity markers (BASDAI and CRP) the logistic regression model was adjusted for the following potential confounders: age, sex, body mass index (BMI), Human Leucocyte Antigen B27 (HLA-B27) status, Bath Ankylosing Spondylitis Metrology Index (BASMI), and current biologic disease-modifying antirheumatic drug treatment (bDMARD). For patients with an available biosample before TNFi initiation, we evaluated drug retention and estimated the hazard ratio of treatment discontinuation depending on anti-CD74 IgA elevation. The TNFi treatment closest to the blood sample collection was selected, regardless of whether it was the first TNFi. The Cox proportional hazard model was adjusted for age, sex, BASDAI, elevated CRP, HLA-B27, and previous bDMARD treatment. Missing covariate values in the Cox proportional hazard model were imputed using multivariate imputation by chained equations (MICE). <h3>Results:</h3> Anti-CD74 IgA were elevated in 383 out of 722 (53%) patients with axSpA and available biosample (s). In the univariable logistic regression models elevated anti-CD74 IgA were associated with older age, male sex, BASMI but not with elevated CRP, BASDAI and HLA-B27. After adjustment anti-CD74 IgA remained significantly associated with older age (OR 1.03, 95% CI 1.01 to 1.05, p=0.01) and were additionally associated with elevated CRP (OR 2.00, 95% CI 1.11 to 3.68, p=0.02), while the associations with male sex, BMI and BASMI lost their significance. After including symptom duration into the regression model, the association with age remained statistically significant. In addition uveitis and radiographic disease status defined by the modified New York criteria were associated with elevated anti-CD74 IgA in the univariable analyses. Uveitis remained significantly associated after adjustment for sex, age, BMI, and HLA-B27 status (OR 2.34, 95% CI 1.51 to 3.69, p < 0.001), whereas the association with radiographic disease status lost its significance after adjustment for sex, age, BASDAI and HLA-B27 status. A total of 310 patients started a TNFi treatment after anti-CD74 IgA measurement. The baseline characteristics of these patients are described in Table 1. Our analysis did not reveal a significant difference in drug retention time between patients with and without elevated anti-CD74 IgA (HR 0.91, 95% CI 0.66 to 1.25, p=0.55) (Figure 1). BASDAI elevation was found to be associated with shorter drug retention, whereas an elevated CRP was associated with a longer retention. <b>Table 1. Baseline characteristics at treatment start.</b> Presented statistics are means (standard deviation), except where indicated otherwise. BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; CRP=C-reactive protein; csDMARD=conventional disease-modifying antirheumatic drug; HLA-B27 = Human Leucocyte Antigen B27; IBD=inflammatory bowel disease; NSAID=nonsteroidal anti-inflammatory drug; TNFi=Tumour Necrosis Factor inhibitor. Figure 1<b>Kaplan-Meier curve of tumour necrosis factor inhibitor retention</b>. Estimated survival curve of patients with and without elevated anti-CD74 IgA. Median retention times are represented by vertical lines. 65 patients with elevated and 53 without elevated anti-CD74 IgA were censored. <h3>Conclusion:</h3> Although elevated anti-CD74 IgA are associated with CRP elevation, we could not demonstrate an additional value of this biomarker for predicting response to treatment with TNFi. Larger studies are needed to confirm our findings. <h3>REFERENCES:</h3> [1] De Craemer AS, Witte T, Lobaton Ortega T, Hoorens A, De Vos M, Cuvelier C, et al. Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation. Rheumatology (Oxford). 2023;62(2):984-990. <h3>Acknowledgements:</h3> <b>NIL</b>. <h3>Disclosure of Interests:</h3> Annik Steimer: None declared, Andrea Goetschi: None declared, Torsten Witte Honoraria for lectures from Abbvie, Alfasigma, Amgen, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, UCB, Patent on CD74 autoantibody measurement, Honoraria for consultation from Abbvie, Alfasigma, Amgen, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, UCB, Almut Scherer: None declared, Jonas Brändli: None declared, Michael J. Nissen Honoraria for lectures from Abbvie, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Honoraria for consultation from Abbvie, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Burkhard Moeller Speaker fees from Eli Lilly, Janssen, Novartis, Pfizer, Grant/research support from Amgen, Simon Grosswiler: None declared, Diego Kyburz Honoraria for lectures from Abbvie, Eli-Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi, Honoraria for consultation from Abbvie, Eli-Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi, Diana Dan: None declared, Andrea Rubbert-Roth Honoraria for lectures from Abbvie, Janssen, MSD, Novartis, Pfizer, UCB, Honoraria for consultation from Abbvie, Janssen, MSD, Novartis, Pfizer, UCB, Sabine Adler: None declared, Oliver Distler Has/had consultancy relationships with and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Acepodia Biotech, Aera, Alcimed, Altavant, Amgen, AnaMar, Anaveon AG, Argenx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Calluna (Arxx), Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, MSD Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Pilan, Prometheus, Quell, Redxpharma, Roivant, EMD Serono, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143). Co-founder of CITUS AG. Research Grants: BI, Kymera, Mitsubishi Tanabe, UCB, Xenofon Baraliakos: None declared, Adrian Ciurea: None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.