Objectives To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years.
Design Swedish nationwide register-based cohort study 1964–2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873.
Results During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn’s disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002–2014 had 2.3 years shorter mean estimated life span than matched comparators.
Conclusions Adult-onset and elderly-onset patients with UC, Crohn’s disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
- Crohn’s disease
- Ulcerative colitis
- IBD unclassified
- Indeterminate IBD
- death cause
- myocardial infarction
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Contributors Guarantor: OO had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: OO, JFL, JA, MCS. Acquisition of data: OO. Analysis: MCS, OO, JFL. Interpretation of data: OO, JA, MCS, MN, KES, AE, JFL. Drafting of the manuscript: JFL, OO, MCS. Critical revision of the manuscript for important intellectual content and approval of final version: OO, JA, MCS, MN, KES, AE, JFL.
Funding OO was supported by grants from the Swedish Medical Society (Project grants SLS-789611)), Swedish Foundation for Strategic Research, and Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF, 20170720, 20170424). JA was supported by the Swedish Cancer Society, the Stockholm County Council (ALF), the Swedish Research Council and the Swedish Foundation for Strategic Research during the conduct of the study. JFL was supported by the FORTE Foundation (83278) and the Swedish Cancer Foundation. None of the funding organisations had any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review and approval of the manuscript.
Competing interests OO has been principal investigator (PI) on projects at Karolinska Institutet partly financed by investigator-initiated grants from Janssen, Ferring, Takeda and Pfizer. None of those studies have any relation to the present study. Karolinska Institutet has received fees for lectures and participation on advisory boards from Janssen, Ferring, Takeda and Pfizer regarding topics not related to the present study. JA reports grants from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Pfizer, Roche, Samsung Bioepis and UCB, mainly in the context of a national safety monitoring programme for immunomodulators in rheumatology (ARTIS). JFL coordinates a study unrelated to the present study on behalf of the Swedish IBD Quality Register (SWIBREG). That study has received funding from Janssen. KES has been PI for research projects partly financed by unrestricted grants from Janssen pharmaceutical to Karolinska Institutet. MN has been PI for research projects unrelated to the current paper and partly financed by investigator-initiated grants from Pfizer and Astra Zeneca to Karolinska Institutet, and has received fees for participation in advisory boards (related to rheumatology). Other authors disclosed no conflicts of interest.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data available due to Swedish regulation.
Author note Several of the researchers care for patients with IBD in their clinical work. The questions addressed in this paper are based on what patients usually want to know. However, in this register-based study no patients were directly involved in the design, recruitment or conduct of the study.
Patient consent for publication Not required.