P929 Relation between Crohn’s disease phenotype and response to ustekinumab in Stockholm – the STOCUSTE study

Abstract Background Ustekinumab, an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of Crohn’s disease, mainly in patients failing tumor necrosis factor alpha inhibitors (aTNF). As Crohn’s presents with different phenotypes, we hypothesized that response to ustekinumab treatment may differ depending on disease characteristics. Methods This retrospective study included 322 unselected patients diagnosed with Crohn’s disease and treated with ustekinumab in Stockholm, Sweden, between 2016 and 2021. The primary outcomes were clinical remission (physician global assessment, PGA =0), response (PGA decrease of ≥1, from baseline), and drug persistence at 3 and 12 months. Subsequently, we calculated odds ratio for drug persistence, clinical response, and clinical remission in relation to several phenotypic disease characteristics. Results Disease location was 15% Ileal (L1), 43% colonic (L2), 41% Ileocolonic (L3), and 7% isolated upper GI (L4), in addition, 22% had fistulizing disease. Some patients had a combination of L4 and L1, L2, or L3. The intention-to-treat response rate was 43% at 3 months, and 42% at 12 months. No difference in outcome was observed in relation to disease location or presence of fistulizing disease. Patients who were >17 years at disease presentation had almost three times the odds for response at 12 months, compared to patients who were < 17 years at diagnosis (Table 1). Almost three times lower clinical remission rates were observed in patients exposed to aTNF agents and vedolizumab prior to ustekinumab, compared to patients exposed to aTNF only (OR 0.38, CI 0.18 – 0.79, p-value 0.01). Higher remission rates were related to age >17 years at disease presentation, however this lost statistical significance in the adjusted logistic regression model. Previously operated patients had double the odds to still be on ustekinumab at 12 months compared to un-operated patients (Table 2). Conclusion In this Stockholm-based Crohn’s disease cohort, the distribution of disease location was well balanced. Considering isolated ileal inflammation and fistulizing disease as markers for disease severity, a substantial part of the cohort had a high disease burden. Nevertheless, there was no statistically significant difference in any of the outcomes in relation to ileal location or fistulizing disease. These results indicate that ustekinumab is a viable treatment option for all location-related phenotypic expressions, as well