Risk of Inflammatory Bowel Disease in Patients with Chronic Myeloproliferative Neoplasms: A Danish Nationwide Cohort Study.

Marie Bak,Henrik Frederiksen,Knud Juel,Tine Jess,Esben Meulengracht Flachs,Ann-Dorthe Zwisler

doi:10.3390/cancers12092700

Abstract

Simple SummaryWe wanted to investigate the risk of inflammatory bowel disease (IBD) in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), since up to 50% of these patients experience gastrointestinal symptoms and several studies have suggested an association between hematological cancers and IBD. We included ∼8000 patients and ∼80,000 sex- and age-matched, non-MPN comparisons from the general population, and found that MPN patients were two to three times more likely to develop IBD, but the absolute risk of IBD was modest. In addition, MPN patients were also 40% more likely to have a prior diagnosis of IBD. Our results pose intriguing questions about the causal pathways linking MPN and IBD, which may include genetic, treatment-related and immune-mediated factors. Moreover, it shows that abdominal symptoms in MPN patients may not only be caused by an enlarged spleen or treatment side-effects. Conversely, persistent leucocytosis and/or increased platelets in IBD patients may reflect concomitant MPN.An association between hematological cancers and inflammatory bowel disease (IBD) has previously been suggested, but the risk of IBD in patients with myeloproliferative neoplasms (MPNs) is unknown. We conducted a nationwide population-based cohort study using Danish registries, to estimate the risk of IBD in individuals diagnosed with essential thrombocythemia, polycythemia vera, myelofibrosis or unclassifiable MPN during 1994–2013. MPN patients were matched 1:10 with sex- and age-matched comparisons. Everyone was followed until a diagnosis of IBD, death/emigration, or 31 December 2013. The risk of IBD overall and according to MPN subtype was calculated using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CI). Of 8207 MPN patients followed for 45,232 person-years, 80 were diagnosed with IBD (61 ulcerative colitis, 19 Crohn’s disease). The rate of IBD per 1000 person-years was 1.8 (95% CI:1.4–2.2) in patients vs. 0.8 (95% CI:0.7–0.8) in comparisons, and the absolute 10-year risk of IBD was 0.8% (95% CI:0.6–1.0) in patients vs. 0.4% (95% CI:0.4–0.5) in comparisons. The HR of IBD was 2.4 (95% CI:2.1–2.9) with similar HRs for ulcerative colitis and Crohn’s disease. MPN subtype risks varied from 2.1 (95% CI:1.6–2.7) to 2.8 (95% CI:2.1–3.7). Our unselected cohort study showed a more than 2-fold increased risk of IBD in MPN patients.

Highlights

For inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), the etiological causes are not entirely known, but in particular, chronic inflammation is a key feature [1,2]
Total IBD, (n) a Individuals who had a recording of either UC or CD or who had a recording of both UC and CD prior to the myeloproliferative neoplasms (MPNs) diagnosis/index date. In this nationwide cohort study of more than 8000 patients with MPN followed for 45,232 person-years, we found a 2.4-fold increased risk of IBD in MPN patients when compared to matched non-MPN comparisons
We found an increased risk of IBD among patients with essential thrombocythemia (ET), polycythemia vera (PV), and MPN-U, but the risk was different over time across the different MPN subtypes and the absolute 10-year risks of IBD were low both for patients with MPN and comparisons—in particular among patients with MF, as only one event was recorded

Summary

Introduction

For inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), the etiological causes are not entirely known, but in particular, chronic inflammation is a key feature [1,2]. Studies show that patients with IBD are at increased risk of various chronic conditions, such as cardio-vascular diseases, osteoporotic fractures, and other immune-mediated diseases [3,4,5,6,7]. The risk of gastrointestinal cancers is increased, as is the risk of some extra-intestinal malignancies, including hematological cancers [8,9,10,11,12,13,14,15]. The subsequent risk of IBD in patients with hematological cancers has not been studied. Chronic myeloproliferative neoplasms (MPNs) are chronic hematological cancers that arise due to clonal hematopoietic stem cell proliferation in the bone marrow. In MF, which is the more advanced form of MPN, characterized by bone marrow fibrosis and dismal prognosis, patients present with elevated leucocytes and/or platelets, or pancytopenia. The etiology of MPNs remains somewhat unknown, but acquired somatic MPN driver mutations in JAK2, MPL or CALR that alter the JAK-STAT signaling pathway are found in most patients [16]

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