OP0254 MICROBIOTA AND CLINICAL RESPONSES TO BIOLOGICAL TREATMENT IN AXIAL SPONDYLOARTHRITIS: INSIGHTS FROM 2 YEAR FOLLOW UP OF THE GESPIC COHORT

Background: Increasing evidence suggest that gut microbiota may contribute to the pathogenesis of axial spondyloarthritis (axSpA), potentially through immune activation and systemic inflammation. It remains unclear how biological disease-modifying antirheumatic drugs (bDMARDs) influence the gut microbiota composition, and whether these changes impact differential treatment outcomes or hold prognostic value. Most existing data are cross-sectional or focused on short-term effects, highlighting a need for prospective longitudinal studies. Objectives: This study aimed to characterize the microbiota composition in patients with radiographic (r-)axSpA undergoing bDMARD therapy identifying microbial signatures predictive of treatment response and explore longitudinal shifts in the gut microbiota between responders and non-responders over a two-year period. Methods: Patients with r-axSpA from an extension arm of the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. Eligibility criteria included high disease activity despite prior intake of nonsteroidal anti-inflammatory drugs and have not received bDMARD therapy for at least three months prior enrollment. The choice of bDMARD therapy followed standard clinical practice at the discretion of the responsible rheumatologist. Disease activity (Axial Spondyloarthritis Disease Activity Score – ASDAS) was assessed at baseline and at each follow-up visit. Fecal samples were collected at baseline and yearly thereafter until year 2. Patients with chronic back pain without a diagnosis of inflammatory disease were included as a control group. Clinical response was defined as a change in ASDAS ≥2.0 points for major improvement (ASDAS-MI) and ≥ 1.1 points for clinically important improvement (ASDAS-CII). Shotgun metagenomic sequencing was performed on 247 fecal samples (62 patients and 62 controls), 237 of which passed quality control. Taxonomic profiling used the CHAMP TM pipeline, which leverages a comprehensive reference catalog of microbial genomes, annotated with GTDB (version r214). Species abundances were rarefied to a fixed number of signature gene counts to account for differences in sequencing depth. Associations with patient characteristics, treatment response, and longitudinal changes were analyzed using linear mixed-effect models, adjusted for baseline disease activity and false discovery rate (FDR) corrections. Results: Among the 62 patients included, 62.3% were male, with a mean age of 38.7 ± 10.7 years at baseline. The prevalence of HLA-B27 was 83.6% among patients and 7.9% among the controls. A total of 81.9% of patients were naïve to bDMARDs at baseline. Patients presented a mean ASDAS of 3.44 ± 0.78 at baseline. The largest decrease in ASDAS occurred between baseline and year 1, reaching clinical response rates of 37.7% for ASDAS-MI and 67.2% for ASDAS-CII at year 1. Alpha diversity showed no significant differences between responders and non-responders at any timepoint. However, non-responders had notably distinct microbiota profiles from other groups, especially at year 1 (Figure 1). Blautia A caecimuris was identified as the main negative predictor for treatment response, with a higher prevalence among non-responders. Higher baseline abundances associated with poor response to bDMARDs. Other species such as Bacteroides xylanisolvens and ER4 sp900317525 (of the Clostridia class) showed the opposite trend, associating with a good clinical response. Temporal changes in the gut microbiota species abundances revealed significant differences between bDMARD therapy responders and non-responders (according to CII) over the two-year period (Figure 2). The strongest microbial shifts were observed in non-responders, with significant increases in Prevotella rara, Dysosmobacter sp944387015, and Bacteroides xylanisolvens ; decreases were observed in Collinsella sp002391315, Bacteroides nordii, and Dysosmobacter faecalis . Interestingly, these species showed no significant changes in responders over the same time period, except for Prevotella rara (increased in responders) and Ventricola sp900542395 (decreased in responders). Conclusion: In this longitudinal analysis, non-responders to bDMARD therapy had distinct microbiota composition at baseline, and presented distinct species shift during treatment. Taxonomic shifts in responders were more subtle, although often in the opposite direction of non-responders. To develop more personalized treatment strategies in axSpA, the present study highlights how metagenomic sequencing is able to unravel persistent fecal signatures with potential prognostic value. REFERENCES: NIL . Acknowledgements: NIL . Disclosure of Interests: Valeria Rios Rodriguez AbbVie and Takeda, AbbVie, Eli Lily, Jannsen, UCB and Pfizer, Morgan Essex: None declared, Murat Torgutalp: None declared, Fabian Proft AbbVie, AMGEN, BMS, Celgene, Janssen, Hexal, Medscape, Moonlake, MSD, Pfizer and Roche, Novartis, Eli Lilly and UCB, Hildrun Haibel Abbvie, Novartis, Pfizer, Janssen, GSK, Sobi, UCB, Abbvie, UCB, Janssen, Sobi, Novartis, Pfizer, Sobi, Novartis, Pfizer, UCB, Alfasigma, Mikhail Protopopov: None declared, Judith Rademacher: None declared, Britta Siegmund AbbVie, AlfaSigma, BMS, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, MSD, Ferring, Galapagos, Janssen, Pfizer, and Takeda, AbbVie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Landos, Lilly, Materia Prima, PredictImmune, Pfizer, and Takeda, Pfizer, Sofia Forslund: None declared, Denis Poddubnyy AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB, AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB. © 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.

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