THU0327 EFFECT OF IMMUNOSUPPRESSIVE MEDICATION ON GASTRO-INTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS PATIENTS STRATIFIED FOR DISEASE DURATION.
Authors: N. Van Leeuwen, H. Fretheim, Ø. Molberg, T. Huizinga, J. De Vries-Bouwstra, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2020)

Background: Gastrointestinal tract (GIT) involvement is associated with high morbidity in systemic sclerosis (SSc) but the data on its impact from unselected and well characterized SSc cohorts are scarce. Currently, the effect of immunosuppressive (IS) treatment on GIT involvement is largely unknown. Objectives: To evaluate the severity and worsening of GIT involvement in two prospective SSc cohorts. To assess factors associated with severity of GIT involvement, stratified for disease duration. To evaluate effect of IS treatment on worsening of GIT involvement. Methods: All SSc patients fulfilling the 2013 SSc classification criteria from two SSc cohorts were evaluated. Incident SSc was defined as disease duration since first symptom non-Raynaud &lt; 24 months at first presentation. GIT involvement was assessed by the UCLA GIT 2.0 score at baseline and after one year to assess worsening of GIT involvement. Worsening was defined as change &gt; minimal clinical important difference for total score and for each of the seven subdomains. GIT involvement was defined as present if the patients reported symptoms resulting in a score of ≥0.01 and was segregated into mild ≥0.01 (&lt;0.5 or for fecal incontinence and distention/bloating &lt;1.01), moderate (≥0.5 or for fecal incontinence and distention/bloating ≥1.01) or severe GI symptoms (&gt; 1.01 or for distension/bloating &gt; 1.61 or for fecal soiling &gt; 2.01). Logistic regression was applied to identify risk factors associated with GIT involvement at baseline. The effect of IS treatment on worsening on each of the subdomains after one year was evaluated with logistic regression, with adjustment for baseline disease duration and severity. Results: In total, 834 SSc patients were included; 236 (28%) had incident disease (table 1). Incident cases (IC) showed comparable severity of GIT involvement compared to non-incident cases (NIC) except for significantly less severe reflux and distension/bloating (figure 1). Logistic regression showed female sex (OR 8.5(1.1-36.01)) and smoking (OR 2.9(1.2-7.3)) to be associated with GIT severity at baseline in IC; in NIC anti-centromere antibody (OR 1.7(1.3-2.2)) was additionally associated with GIT severity. The use of IS at baseline did not associate with GI severity at baseline. In total n = 685 (82% never had IS treatment (83% NIC, 81% IC); of these 258 (38%) started with IS after baseline assessment (52% IC, 32% NIC, p =0.02). When comparing change of GIT involvement after one year between those who started IS and those who did not, worsening of GI symptoms occurred more frequently in patients who started IS treatment (figure 2), but notably, patients in this group were also more frequently anti-topoisomerase positive, had ILD, and diffuse disease subset compared to the patients without IS treatment; age and sex were comparable. In the logistic regression with adjustment for disease duration and severity, there were no significant associations between IS treatment and worsening on GIT involvement. Conclusion: Regardless disease duration, about 1/3 of all SSc patients had moderate-severe GIT involvement. Disease duration and treatment initiation with IS did not have a significant influence on worsening of GIT involvement. Table: Baseline characteristics Non-inception cohort (n=598) Inception cohort (n=236) Female, n(%) 504 (85) 180 (76) Age, mean(SD) 55 (13) 56 (14) Disease duration non Raynaud-Phenomenon, median (IQR) 8.8 (4.8-14.4) 0.7 (0.3-1.2) Diffuse cutaneous subset, n(%) 119 (20) 67 (28) Interstitial lung disease, n(%) 233 (39) 71 (30) Anti-centromere, n(%) 296 (50) 96 (41) Immunosuppresive treatment at baseline, n(%) 102 (17) 44 (19)) Duration of treatment at baseline in years, mean (SD) 4.1 (4.8) 1.2 (2.9) Methotrexate, n(%) 54 (9) 24 (10) Mycophenolate mofetil, n(%) 25 (4) 13 (6) Hydroxycholoquine, n(%) 20 (3) 7 (3) Cyclofosfamide, n(%) 1 (1) 10 (4) Azathioprine, n(%) 11 (2) 2 (1) Corticosteroids, n(%) 58 (10) 27 (11) Acknowledgments: NA Disclosure of Interests: Nina van Leeuwen: None declared, Håvard Fretheim: None declared, Øyvind Molberg: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Jeska de Vries-Bouwstra: None declared, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche