Introduction
Head-to-head (H2H) comparisons of biologics and small molecules in randomised clinical trials (RCTs) are considered the gold standard in inflammatory bowel disease (IBD). However, comparative real-world evidence (RWE) registry studies can provide important additional knowledge. Our aim is to perform a range of such H2H RWE studies, including subgroup analyses, to examine different treatments in patients with IBD. To do so, we draw upon data from a large data warehouse (UMBRELLA-IBD), which pools data from all eight prospective RWE registries in the Competence Network IBD. All patients were recruited to each registry in a similar manner.
Aims & Methods
Pooled analyses have a range of important methodological and logistical requirements, all of which are met in the eight prospective RWE registries that feed data into the UMBRELLA-IBD data warehouse: (1) The prospectively collected data are highly homogeneous, with each registry using similar inclusion and exclusion criteria, and the analyses of registry data using similar outcome parameters; (2) The quality of the data is high, and the data are comparable due to comprehensive remote and onsite monitoring; (3) The advanced statistical methods used to compensate for the absence of randomisation include propensity score adjustment with inverse probability of treatment weighting (IPTW) and are applied similarly in each analysis (Table 1). In concordance with a priori protocols, data and parameters from the eight Competence Network IBD registries were checked for consistency, merged and then migrated to a common server. Additionally, a data validation plan (DVP) was created to process all data, with individual items being adapted by appropriate recoding for the pooled evaluation.
Results
In the new UMBRELLA-IBD data warehouse of the Competence Network IBD, prospectively recorded data from a total of 6,689 IBD patients in eight registry studies in Germany are available for a planned pooled analysis (Table 1), albeit with some patients potentially having been recruited to more than one of these studies. As of 31 March 2023, 35% of the patients included in the data warehouse are biologic-naïve and started their first biologic/small molecule treatment at recruitment. Prospectively documented one-year records are available for 75% of patients, and supplementary biomaterials have been collected in 40% of patients. Recruitment and follow-up are ongoing in some registries.
Table 1: IBD patients in the prospective registries of the Competence Network IBD at a glance: Umbrella-IBD (as of 31 March 2023)
* Some patients may be recruited in more than one study
| Prospective RWE registries in the Competence Network IBD | Patients with IBD | Study duration | Bio-naïve
patients | Pts. with short course of disease | CD/UC | Biomaterials in
(%) of patients | Month 12 visit
documented |
| BioCrohn | 1,530 | 2008 - 2018 | 393 | 677 (< 3 years) | CD | 85% | 1,216 |
| BioColitis | 883 | 2013 - 2021 | 238 | 447 (< 2 years) | UC | 51% | 666 |
| Run-CD | 901 | 2017 - 2024 | 301 | - | CD | 30% | 802 |
| VEDO-IBD | 1,284 | 2017 - 2022 | 824 | 150 (< 2 years) | CD/UC | 51% | 937 |
| IBD-Inception Registry | 140 | 2016 - 2019 |
| 140 (< 1 year) | CD/UC | - | 110 |
| RUN-UC | 507 | 2020 -2024 | 238 | - | UC | - | 387 |
| FilgoColitis | 162 | 2022 - 2025 | 22 | - | UC | - | 28 |
| TARGET | 1,282 | 2019 - ongoing | 308 | - | CD/UC | - | 861 |
| IBD patients included in total* | 6,689 | 2008 - today | 2,324 | 1414 | CD/UC |
| 5,007 |
Conclusion
The large UMBRELLA-IBD RWE data warehouse from eight different prospective Competence Network IBD registries is a promising initiative for conducting further comparative studies that will provide important evidence in addition to that from existing RCTs in IBD patients.
Disclosure
BB has received consulting fees from: AbbVie, MSD, Shire, Ferring, Hospira, Takeda, Galapagos, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, and Celgene, outside the submitted work. Financial support for lectures and teaching from: AbbVie, Ferring, MSD, Merckle, Falk, Galapagos, Shield Therapeutics, Pfizer, Celltrion, Takeda, and Janssen. Grant and financial support for research from AbbVie, Takeda, Jansen, Pfizer, Galapagos, and Ferring, outside the submitted work. SPD has no relevant financial or non-financial interests to disclose. TW has no relevant financial or non-financial interests to disclose. EG has no relevant financial or non-financial interests to disclose. FT receives scientific funding from Sanofi, received consulting fee's from LEK Consulting and speaker's fee from Lilly, Janssen, Falk, Abbvie, Celltrion, onkowissen.de, CED Service GmbH. AB received consulting and speaker's fee from Abbvie, Amgen, BMS, Falk, Ferring, Janssen, Pfizer, Sanofi and Takeda. SS has served as a consultant or advisory board member for AbbVie, Amgen, Arena, Bristol Myers Squibb, Biogen, Celltrion, Celgene, Ferring, Fresenius, Galapagos, Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance and UCB.