(B17) Comparison of biologic use in pivotal clinical trials vs. real-world setting with immune-mediated inflammatory diseases: an Italian population-based study from the VALORE project
Assistant Professor Department of Diagnostics and Public Health, University of Verona, Verona, Italy
Background: Patients enrolled into pivotal randomized controlled trials (RCTs) typically differ from those treated in the real-world (RW) setting.
Objectives: To assess the generalizability of findings from pivotal RCT of biologics approved for immune-mediated inflammatory diseases (IMIDs) by exploring the differences in demographic characteristics between RCTs’ vs. RW setting using the Italian VALORE distributed database network. The extent of biological drug users treated for IMID in RW that would not have been eligible for inclusion into RCT was also measured.
Methods: All the indication of use-specific pivotal phase III RCTs of biologics approved for IMIDs up to 2020 were collected. Using validated coding algorithms, incident RW users of biologics approved for most frequent IMIDs, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), psoriasis (PsO), Crohn’s disease (CD) or ulcerative colitis (UC), were identified from claims databases of eight regions (2010-2020). For each indication for use, demographic characteristics of subjects enrolled in pivotal RCTs were compared with those of biologic users from RW setting. Inclusion/exclusion criteria reported in pivotal RCTs were identified and applied to RW population, to calculate the proportion of biologics who would not have been eligible for inclusion in RCTs.
Results: Overall, 37,807 and 66,639 incident users of 17 biologics approved for IMIDs were identified from pivotal RCTs and RW setting, respectively. No statistically significant differences of sex distribution between RCTs and RW population were observed, except for certolizumab pegol in AS/PsO/PsA, more commonly used by RW females (>AS:64.3%; PsO: 62.4%; PsA: 65.5%) than RCT females (AS: 32.5-39.5%; PsO: 30.6-43.3%; PsA: 53.8%). RCTs patients were slightly younger (45±15 years) than RW patients (48±16 years), especially ustekinumab and vedolizumab users with inflammatory bowel diseases. A high proportion of biologic users from RW setting would have been ineligible for inclusion in pivotal RCTs, according to the inclusion/exclusion criteria (22-81%).
Conclusions: Demographic characteristics of IMIDs patients treated with biologics in Italian real-world setting are different of those enrolled in pivotal RCTs. A high proportion of RW users would have been ineligible for inclusion in pivotal RCTs and as such post-marketing surveillance of biologics should be prioritized in those patients.
