Medical and surgical treatment of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), with its two main entities Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory condition affecting the entire gastrointestinal tract. IBD is associated with reduced health-related quality of life, substantial loss of work productivity and increased morbidity. In Sweden alone, around 70 000 persons are estimated to be affected by IBD. Treatment includes both medical and surgical therapy. In case of failure or intolerance to conventional medical therapies, remaining treatment options are surgery or newer medical therapies such as biological agents. However, a sizeable number of patients do not respond or lose response to a certain biological agent, hence there is still a need to expand the knowledge about therapeutic options in IBD. This thesis therefore aimed to explored real-world clinical outcomes of a recent biological therapy. Using registered-based data, the thesis also investigated epidemiological aspects of IBD including the validity of IBD-related surgical procedure codes and the incidence of IBD in Sweden.

In Study I, we validated IBD-related surgical procedure codes in the Swedish National Patient Register (NPR). We conducted the validation through patient chart review in a nationwide random sample of 262 patients with registered IBD diagnoses in the NPR between 1966 and 2014. We found high validity and high sensitivity for IBD-related surgical procedure codes in the NPR with a positive predictive value of 96.8% and a sensitivity of 94.5%. Our study indicated that the NPR is a reliable data source for researchers wanting to identify patients with a history of IBD-related surgery.

In Studies II and III, we conducted a nationwide prospective observational real-world study of clinical, biochemical and health-related quality of life outcomes in CD patients treated with ustekinumab according to clinical practice. We included a total of 114 patients initiated on ustekinumab treatment during 2017 and 2018 at 20 different hospitals. We found significant improvements of almost all outcome measures and both short-term (Study II) and long-term (Study III) response and remission to treatment. Our study contributes to the knowledge about the real-world effectiveness and safety of ustekinumab for treatment of moderate to severe CD.

In Study IV, we estimated the nationwide incidence of IBD and subtypes (CD, UC and IBDunclassified) and investigated differences between age-groups and sexes in Sweden 1990- 2014. We used a combination of diagnostic codes for IBD in the NPR and biopsy data from the ESPRESSO histopathology cohort to identify incident cases (N=65 908) during the study period. We found evidence of increasing incidence rates (IRs) in all subtypes 1990-2001, but signs of stabilising or decreasing IRs 2002-2014. We also showed differences in IRs between males and females related to age and calendar period. Our results contribute to the knowledge about temporal trends of IBD incidence in Sweden of importance for future research, and possibly also for healthcare resource planners.

In conclusion, this thesis gave evidence of the NPR as a reliable and valid data source for researchers wanting to identify patients with previous IBD-related surgery. It also enhanced knowledge about the real-world effectiveness of ustkinumab, beneficial for patients suffering from CD. Finally, it shed light on previous contradicting estimates of the temporal trends of the incidence of IBD in Sweden.