POS0237 GUT DYSBIOSIS LINKED TO WORSE DISEASE STATUS IN AXIAL SPONDYLOARTHRITIS
Authors: J. Sagard, T. Olofsson, E. Mogard, J. Marsal, K. Andréasson, M. Geijer, L. E. Kristensen, E. Lindqvist, J. K. Wallman
Journal: Annals of the Rheumatic Diseases (2021)

Background: Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. Objectives: To compare presence and degree of gut dysbiosis between axSpA patients and controls, and to explore whether gut dysbiosis is associated with axSpA disease activity, function and pain. Methods: The GA-map Dysbiosis Test (Genetic Analysis, Oslo, Norway) was used to identify and grade gut dysbiosis based on faecal samples from 44 non-radiographic axSpA (nr-axSpA; ASAS criteria) and 88 ankylosing spondylitis (AS; modified New York criteria) patients without IBD, consecutively enrolled in a population-based cohort study, and from 46 controls without rheumatic disease or IBD (frequency-matched to the patients for age/sex). The GA-map Dysbiosis Test is a validated method grading microbiota aberration on a 1-5 scale (Dysbiosis Index, DI), where ≥3 denotes dysbiosis. Analysis of covariance (ANCOVA) was used to compare DI between axSpA patients (nr-axSpA and AS combined) and controls, adjusted for age, sex, body mass index (BMI) and smoking. Within the axSpA group, disease activity (ASDAS-CRP; BASDAI), function (BASFI) and pain (VAS pain) were compared between patients with various DI levels by One-way analysis of variance (ANOVA) or Kruskal-Wallis test, as appropriate. Finally, axSpA patients were subdivided by presence of dysbiosis (DI ≥3 vs. &lt;3) followed by comparison of ASDAS-CRP, BASDAI, BASFI, VAS pain and Evaluator´s global assessment of disease activity (EvalGlobal; 0-4: remission-maximal) by ANCOVA. Analyses were conducted unadjusted and adjusted for age, sex, BMI, smoking, axSpA subtype, gut inflammation (faecal calprotectin ≥50 mg/kg), irritable bowel syndrome symptoms (ROME III criteria), ASAS 3-month NSAID score and cs/bDMARD treatment. Results: Characteristics of the patients/controls are shown in the Table 1. Gut dysbiosis (DI≥3) was observed in 33% of axSpA patients and 17% of controls. DI was significantly higher among the patients (β-estimate [bootstrapped 95%CI] for the between-group difference: 0.34 [0.04-0.65]; p=0.027). In the axSpA group, higher DI was associated with worse scores in all assessed outcomes (Figure 1, panel A). Moreover, presence of dysbiosis (DI≥3) was associated with worse ASDAS-CRP, BASDAI, BASFI, VAS pain and EvalGlobal (Figure 1, panel B; EvalGlobal not shown in the Figure: unadjusted β [bootstrapped 95%CI]: 0.32 [0.09-0.55], adjusted: 0.28 [0.03-0.52] for patients with DI ≥3 vs. &lt;3), with between-group differences remaining significant after adjustment, except for ASDAS-CRP (p=0.079) and VAS pain (p=0.064). Table 1. All patients n=132 Nr-axSpA n=44 AS n=88 Controls n=46 Male sex, n (%) 72 (55) 17 (39) 55 (63) 23 (50) Age, y 53 (13) 48 (12) 55 (13) 51 (14) Symptom duration, y 26 (14) 21 (11) 28 (14) Body mass index, kg/m 2 27 (4.3) 27 (4.2) 27 (4.3) 25 (3.3) Smoking ever, n (%) 43 (33) 9 (20) 34 (39) 13 (28) CRP, mg/L 3.7 (5.3) 2.3 (2.4) 4.3 (6.1) F-Calprotectin ≥50 mg/kg, n (%) 46 (35) 12 (27) 34 (39) Evaluator´s global, 0-4, median (IQR) 1 (0-1) 1 (0-1) 1 (0-1) ASDAS-CRP 1.8 (0.9) 1.9 (0.9) 1.8 (0.9) BASDAI 3.1 (2.2) 3.3 (1.9) 3.0 (2.4) BASFI 2.0 (2.1) 2.0 (1.7) 2.1 (2.2) VAS pain, cm 3.3 (2.5) 3.4 (2.2) 3.2 (2.7) IBS symptoms, n (%) 43 (33) 15 (34) 28 (32) ASAS 3-month NSAID score 37 (44) 36 (44) 37 (44) Ongoing csDMARD, n (%) 24 (18) 9 (20) 15 (17) Ongoing bDMARD, n (%) 56 (42) 19 (43) 37 (42) Mean (SD) unless otherwise specified. y, years; IBS, irritable bowel syndrome Conclusion: Gut dysbiosis, present to a higher degree in axSpA patients than controls, is associated with worse axSpA disease activity and function. These associations appear independent of gut inflammation and both NSAID and immunomodulatory treatment. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA manifestations, and implies that gut dysbiosis may be a novel biomarker for severe disease. Disclosure of Interests: Jonas Sagard: None declared, Tor Olofsson Consultant of: Eli Lilly, Merck Sharp &amp; Dohme, Elisabeth Mogard: None declared, Jan Marsal Consultant of: AbbVie, Bristol-Myers Squibb, EuroDiagnostica, Ferring, Hospira, Janssen-Cilag, Merck, Sharp &amp; Dohme (MSD), Otsuka, Pfizer, Sandoz, Takeda, Tillotts, UCB Pharma, Grant/research support from: AbbVie, Ferring, and Pfizer, Kristofer Andréasson: None declared, Mats Geijer Speakers bureau: UCB Pharma, AbbVie, Novartis, Pfizer, Lars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, Janssen pharmaceuticals, Consultant of: Pfizer, AbbVie, Amgen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, Janssen pharmaceuticals, Elisabet Lindqvist: None declared, Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis