Data from Stephen Smith - Curated by EPG Health - Last updated 23 October 2018
The course of IBD and the risk of comorbid cancer
Crohn’s disease and ulcerative colitis are not stable, static conditions but progressive inflammatory diseases that evolve over time resulting in changing behaviour and localisation. However, the clinical course of IBD requires further elucidation and it remains unclear as to how it differs between populations and patients. Meanwhile, the inflammatory nature of the condition and the associated use of immunosuppressants means IBD has been linked with an increased risk of cancer. How significant are these risks though? In this article, we provide an overview of some of the presentations and posters at UEG Week 2018 that studied the course of IBD and investigated the associated risk of cancer.
The course of Crohn’s disease
Patients with Crohn’s disease frequently see a progression in their disease to worsening behaviour while the presence of transmural inflammation can result in stricturing and/or penetrating complications. Is this typical though? At what rate does the disease progress? This question was investigated by Dr Cátia Arieira from the Hospital da Senhora da Oliveira in Guimarães, Portugal.
In this retrospective study of 290 patients with Crohn’s disease, 15.9% of patients experienced a change in behaviour over a follow-up period of at least 12 months. Among those patients, 65.2% saw their disease change from inflammatory to structuring, 15.2% went from structuring to penetrating and 19.6% went from inflammatory to penetrating. Risk factors associated with changing phenotype included ileocolic location (6.9% vs. 45.1%; p=0.049), aged less than 16 at diagnosis (8.7 vs. 2%; p=0.017), the use of steroids at diagnosis (43.2% vs. 27%; p=0.031) and less exposure time to biological therapy (15.9 months vs. 41.3 months; p<0.001).
Dr Arieira and colleagues also assessed the risk of patients undergoing surgery. In this cohort, 24.1% of patients required surgery with an elevated risk observed in patients who smoked (42.9% vs. 24.8%; p=0.004), structuring behaviour (47.1% vs. 15.9%; p<0.001), penetrating behaviour (42.9% vs. 2.3%; p<0.001), hospitalisations in the first year of diagnosis (52.3% vs. 12.4%; p<0.001) and use of steroids at diagnosis (61.4% vs. 23.6%; p<0.001). Interestingly, and in support of data in yesterday’s article , patients who required surgery were less frequently treated with biological therapy (8.7% vs. 23.4%; p<0.025).
Comparing childhood-, adult- and elderly-onset IBD
While Dr Arieria identified several factors associated with an unfavourable clinical evolution, is this consistent across different populations? Dr María Chaparro from the Hospital Universitario de La Princesa in Madrid, Spain compared the characteristics and treatment of childhood-(diagnosed ≤16 years old) and adult-onset (diagnosed >16 years old) IBD.
Among a cohort of 21,200 patients (96% adult-onset IBD), those with childhood-onset IBD were more likely to be male, have Crohn’s disease and a family history of IBD than those in the adult group. Patients with Crohn’s disease in the childhood group also had more extensive involvement but were less likely to have a stricturing or fistulising phenotype than those in the adult group while patients with childhood-onset ulcerative colitis also had more extensive involvement than adult patients.
The use of immunomodulators, biologics and surgery to manage IBD was also assessed for the childhood- and adult-onset groups. Over the course of 5 years of follow-up, the use of immunomodulators was significantly higher in the childhood-onset group than the adult group (HR 1.6; 95% CI, 1.5–1.8; p<0.01). Similarly, childhood-onset patients were more likely to receive biological therapies over the course of their treatment than adult-onset patients (HR 1.5; 95% CI, 1.4–1.7; p<0.01) (Figure 1).
Figure 1: Cumulative incidence of exposure to biologics in childhood- and adult-onset IBD patients
Interestingly, the cumulative incidence of surgery was not significantly different between the groups (HR 0.9; 95% CI, 0.8–1.2; p=not significant). Are similar differences seen in elderly-onset IBD? A poster presented by Dr Vincent Hernández Ramírez from Hospital Alvaro Cunqueiro, Vigo, Spain addressed this question by exploring the incidence, presentation and treatment of IBD in patients aged ≥60 years at diagnosis and comparing it to patients aged between 15–39 years and 40–59 years. In this cohort of 2,000 patients, the incidence of Crohn’s disease in each age group was 7.18 (15–39), 3.95 (40–59) and 2.70 (≥60) cases/105 patients (p<0.001). While the incidence of Crohn’s disease was less common among elderly-onset patients, it was more likely to have a colonic location. Patients with elderly-onset IBD were more likely to be diagnosed with ulcerative colitis with an incidence rate of 9.58, 6.30 and 5.68 for each of the patient age groups, respectively.
Interestingly, the incidence of Crohn’s disease significantly dropped across each age group, whereas ulcerative colitis appeared to plateau with a comparable incidence in patients aged between 40–59 years and in the elderly group. When it comes to the treatment of IBD, elderly patients were less likely to receive intensive treatment in the first three months after diagnosis. In Crohn’s disease, elderly patients were less likely to receive an immunomodulator or biologic therapy whereas patients with elderly-onset ulcerative colitis were more likely to receive topical steroids and less likely to be prescribed aminosalicylates (5-ASA) or an immunomodulator. This may be a consequence of differences in disease severity, or perhaps due to the presence of other comorbidities, but additional research is required to understand this further.
IBD and comorbid cancer
IBD has previously been linked to increased rates of cancer. However, the magnitude of the risk remains uncertain, especially with the advent of new, more targeted therapies.
One such cancer grouping that has been linked to immunosuppressive treatment in IBD is non-melanoma skin cancer (NMSC). Does the addition of new treatments to the IBD armamentarium affect this risk and does their earlier introduction and longer use have any bearing on the incidence of skin cancer? Dr Catriona Gallagher from Tallaght Hospital, Dublin, Ireland presented retrospective data assessing the incidence of NMSC and malignant melanoma among 931 patients with IBD and 1,090 age- and sex-matched controls. As expected, the incidence of NMSC was significantly higher in patients with IBD than the control group (1.18% vs. 0.28%; p<0.03; RR 1.7; 95% CI, 1.29–2.26). However, while the incidence of malignant melanoma was also higher in patients with IBD than controls, it did not reach statistical significance (0.43% vs. 0.09%; p=0.18; RR 1.7, 95% CI 1.12–2.70) suggesting that a larger cohort of patients may be needed to establish this link. Despite this, it was shown that patients with malignant melanoma were younger than patients with NMSC (51.4 years vs. 72.3 years; p<0.004) suggesting that younger patients with IBD are at a higher risk of malignant melanoma than older patients. With Dr Gallagher suggesting the establishment of an IBD-specific skin cancer awareness campaign, are other cancer types also associated with IBD and its treatment?
IBD has been associated with an increased risk of gastrointestinal cancer with risk factors likely to be the duration and degree of inflammation as well as how extensive the disease is. Dr Petra Weimers from North Zealand University Hospital, Frederikssund, Denmark looked to estimate the prevalence of GI cancers in a Danish nationwide population cohort of all incident adult patients between 1997 and 2015. An IBD cohort of 35,910 patients (67.1% ulcerative colitis, 27.1% Crohn’s disease; 5.8% IBD-unclassified) and matched to 1,747,002 reference controls.
Overall 12.0% of patients with IBD were diagnosed with one or more cancers compared to 10.0% of the control group (p<0.001). However, the prevalence differed between tumour- and IBD-type (Figure 2).
Figure 2: Incidence of different cancer types in study population. *Including patients with two or more cancers; †p<0.05, ‡p<0.001 vs. controls; CD = Crohn’s disease, IBDU = IBD unclassified, UC = ulcerative colitis.
This nationwide cohort of Danish patients with IBD suggests that people living with IBD have an increased risk of cancer compared to the general population and improves our understanding of which cancers may be more prevalent in these patients.
Some fascinating insights highlighting the differences between IBD populations have been shared at UEG Week 2018. Join us again tomorrow where we will be discussing some of the latest data on management strategies in IBD.