P881 Real-life vs trial access to biologic therapy differences: a 2019-2020 experience in an Italian tertiary IBD center
Authors: DI VINCENZO F , Maresca R , Mora V , Petito V , Turchini L , Amatucci V , Napolitano D , Schiavoni E , Lopetuso L R , Parisio L , Settanni C R , Pizzoferrato M , Armuzzi A , Pugliese D , Laterza L , Gasbarrini A , Scaldaferri F 
Published: January 2024

Abstract

Background
Inflammatory Bowel Diseases (IBD) are multifactorial diseases including Ulcerative Colitis (UC) and Crohn's Disease (CD). Up to 50% of IBD patients show a primary or secondary non-response to standard biological therapy. Hence, Randomized Clinical Trials (RCTs) represent a significant therapeutic opportunity for them.
This study aims to describe the clinical characteristics of "trial IBD patients" vs. "real-life IBD".

Methods
We prospectively enrolled patients who started biologic therapy from August 2019 to August 2020. We divided patients into 3 sub-groups: (1) "real-life", patients treated according to clinical practice with biologic therapy that did not meet the inclusion and exclusion criteria for RCTs, (2) "real-life suitable for trial", patients potentially eligible in RCTs, but treated with standard of care, and (3) "trial", patients treated with drugs from 14 phases 2b and 3 studies actively recruiting in our center.

Results
We enrolled 134 patients (72 UC, 62 CD). "Real-life" patients were 41 in UC and 38 in CD, "real-life suitable for trial" were 6 in UC and 14 in CD, and "trial" were 25 in UC and 10 in CD.
According to the existing inclusion and exclusion criteria, the study showed that 43% UC patients and 39% CD were suitable for enrollment in RCTs, however only 16% of CD were finally enrolled in RCTs. At the enrollment, patients were mainly excluded for topical therapy use, cancer, recent infections, low CDAI (&lt;220) or SED-CD (&lt;6), or presence of complication of diseases in CD or for limited extension of disease in UC.
Both "trial" UC and CD patients presented more extraintestinal manifestations of disease, especially the articular ones (p&lt;0,05) and a higher significant concomitant use of systemic corticosteroids (≤20mg/die (p &lt; 0,05)). Percentages of patients treated previously with other biological drugs were superior in "trial" patients compared to "real-life" only in UC (88% vs 29%). We observed different baseline clinical disease activity scores in CD: the HBI of "real-life" patients was 4.8, and the HBI of "trial" patients was 9.1.
In addition, patients enrolled in RCTs waited longer before accessing the proposed biological therapy.

Conclusion
This study highlights some differences between clinical practice and RCTs, particularly regarding criteria to start biologic therapy. Globally "trial patients" have more complex diseases that significantly impact their clinical status. Furthermore, RCTs use clinical scores (e.g. CDAI) as determinants for enrollment and decision-making, while endoscopy and radiological imaging are more widely used in clinical practice for decision making. These differences could cover the actual effectiveness of a new drug compared to the theoretical efficacy deriving from registration RCTs.