Primary sclerosing cholangitis-inflammatory bowel disease: Epidemiology, mortality, and impact of diagnostic sequence.

Background & Aims: Primary sclerosing cholangitis (PSC) carries significant morbidity and mortality compared with inflammatory bowel disease (IBD). We characterized epidemiology trends and outcomes in those with PSC-IBD and IBD, paying particular attention to the impact of PSC-IBD diagnostic sequence on outcomes. Methods: Incidence and prevalence of PSC-IBD and IBD (2002-2018) were evaluated using validated health administrative data-derived cohorts from Ontario, Canada (population ∼15 million). Transplant and death outcomes were assessed, with PSC-IBD diagnostic sequence as the exposure of interest. Results: Incidence of PSC-IBD and IBD was 0.46 and 24.6/100,000 person-years (PYs) respectively, whereas prevalence was 5.53 and 588/100,000 PY respectively. Incidence/prevalence of PSC-IBD increased over time, unlike for IBD. Age at IBD diagnosis was earlier among those with PSC-IBD compared with those with IBD alone. Higher socioeconomic status associated with high PSC-IBD incidence rates and fastest incidence rise. Those diagnosed with IBD before PSC had higher risk of transplant/death compared with PSC before IBD (hazard ratio [HR] 1.34, 95% CI 1.02-1.75), driven by an increased risk of death (HR 2.73, 95% CI 1.68-4.45). PSC-IBD had a 4.5-fold greater risk of transplant/death compared with IBD alone. Liver-related and luminal gastrointestinal disease, particularly hepatopancreatobiliary malignancy, were predominant causes of death among those with PSC-IBD, while cardiovascular and respiratory diseases were predominant among those with IBD. Conclusions: Population-level data support distinct epidemiological patterns among people living with PSC-IBD compared with IBD, including a higher socioeconomic status and worse outcomes in those found to have IBD before PSC. Impact and implications: Individuals with primary sclerosing cholangitis (PSC) face increased morbidity and mortality compared with the general population and those with inflammatory bowel disease (IBD); yet, most individuals with PSC are found to have concomitant IBD during their lifetime. This study describes the distinctive epidemiological differences and mortality trends at the population level between PSC-IBD and IBD. While PSC-IBD remains a rare condition, diagnoses are on the rise (particularly among higher socioeconomic status populations), with most patients being diagnosed with IBD before PSC; this group also experienced higher mortality post-PSC diagnosis compared with those diagnosed with PSC first, with a large proportion of deaths caused by liver- and gut-related causes. Practical applications of these findings include further studies to evaluate whether earlier identification of PSC-IBD affects disease outcomes, as well as educating patients, clinicians, and policymakers on the importance of recognizing PSC-IBD as a distinct entity from IBD alone.