Anti-tumour necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study.

BACKGROUND: Safety of anti-tumour necrosis factor-α (TNFα) therapy in people with a history of cancer and with an immune-mediated disease is unknown. We aimed to assess the risk of recurrence of initial cancer or development of a new primary cancer after treatment with anti-TNFα therapy. METHODS: In this Danish, population-based cohort study we recruited adults (≥18 years) with inflammatory bowel disease (IBD), rheumatoid arthritis, or psoriasis and a primary cancer diagnosed between Jan 1, 1999 and Dec 31, 2016. Patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Participants were matched 1:10 between the treatment group who received anti-TNFα therapy and the control group (no anti-TNFα therapy) and we excluded individuals with a cancer diagnosed before their first anti-TNFα treatment (or before matching date for controls), individuals diagnosed with IBD, rheumatoid arthritis, or psoriasis after anti-TNFα initiation (or respective match date for controls), and individuals who received anti-TNFα with fewer than five matched controls. Using adjusted Cox proportional hazards regression, we estimated the primary outcome of development of recurrent or new primary cancer in patients who received anti-TNFα therapy compared with patients who did not receive this therapy, matched by sex, immune-mediated disease type, cancer type, and time from initial cancer diagnosis to first anti-TNFα registration. FINDINGS: Overall, 25 738 patients with immune-mediated disease and a history of cancer were identified. 434 patients who received anti-TNFα therapy after their initial cancer were matched to 4328 patients in the control group. During 18 752 person-years (median 5·6 years [IQR 2·8-7·9]) of follow up, 635 individuals developed recurrent or new primary cancer, 72 of whom had received anti-TNFα therapy and 563 of whom were in the control group. The median time between anti-TNFα treatment and recurrent or new primary cancer diagnosis was 2·8 years (IQR 1·7-5·4). The incidence of recurrent or new primary cancer development was 30·3 cases (95% CI 24·0-38·2) per 1000 person-years in the anti-TNFα treatment group and 34·4 cases (31·7-37·3) per 1000 person-years in the control group, yielding an adjusted hazard ratio of 0·82 (95% CI 0·61-1·11). INTERPRETATION: Use of anti-TNFα therapy was not associated with recurrent or new primary cancer development in patients with previous cancer. Timing of anti-TNFα therapy after an initial cancer diagnosis did not influence recurrent or new primary cancer development. This observation might guide clinical decision making among providers treating immune-mediated diseases with anti-TNFα medications. FUNDING: None.

Childhood growth and risk of inflammatory bowel disease: a population-based study of 317,030 children.

Background: Growth in childhood is associated with later development of autoimmune diseases and cancer, but the impact of growth on risk of inflammatory bowel disease (IBD) remains unknown. We conducted a population-based cohort study to examine whether birth weight, childhood height, or changes in height associated with later risk of IBD. Methods: Our cohort consisted of 317,030 children from the Copenhagen School Health Records Register (born 1930-1989) with height repeatedly measured from age 7 to 13 and with data on birth weight on a subset. Through linkage to the Danish National Patients Register, cases of IBD were identified. Cox proportional hazard regression was used to examine associations between measures of childhood growth and risk of IBD. Results: During more than 9 million years of follow-up, 1612 individuals were diagnosed with Crohn's disease (CD) and 2,640 with ulcerative colitis (UC). Birth weight and childhood heights were not associated with subsequent risk of CD or UC (HRs close to 1.00). Childhood growth from 7 to 10 years (CD: HR, 1.00; 95% CI, 0.85-1.18; UC: HR, 0.92; 95% CI, 0.81-1.05) and 10 to 13 years (CD: HR, 1.02; 95% CI, 0.89-1.17; UC: HR, 0.95; 0.85-1.05) did not associate with risk of IBD either. Conclusion: In this large population-based cohort study, birth weight and childhood growth did not influence risk of IBD, which contrasts with observations in other chronic diseases. Thereby, the study also suggests that pre-clinical effects of adult IBD are not measurable in childhood and that childhood risk factors for IBD do not influence growth.

Body mass index in young men and risk of inflammatory bowel disease through adult life: A population-based Danish cohort study.

Body mass index (BMI) is associated with increased future risk of inflammatory bowel disease(IBD) particularly Crohn's disease(CD), where associations with high and low BMI have been observed. Most studies are based on adult women. We aimed to explore the impact of BMI in men entering adult life on their long-term risk of developing IBD. A total of 377,957 men born during 1939-1959, with BMI measured at draft boards at mean age 19, were followed from 1977, or time of examination, to end of 2015. Risk of IBD was assessed using Cox regression. During 13 million person-years of follow-up, 1,523 developed CD and 3,323 UC. Using normal weight as reference, for CD the following HRs were observed: BMI < 18.5, 1.35; 95% CI, 1.12-1.62, BMI 25-29.9; 0.83; 95% CI, 0.68-1.02. and BMI > 30 1.20; 95% CI, 0.75-1.90). The increased risk of CD in underweight was maintained up until age 60 not explained by known effects of smoking. For UC, minor inverse associations were observed. Restricted cubic splines revealed a U-shape association between BMI and CD, but not UC. Low BMI of men entering adult life is associated with an increased incidence of CD and UC up to 40 years later.

Childhood body mass index and risk of inflammatory bowel disease in adulthood: a population-based cohort study.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) in western countries has led to the hypothesis that obesity-related inflammation could play a role in the etiology of IBD. However, this hypothesis lacks confirmation in studies of individuals prior to the typical onset of IBD in young adulthood. METHODS: In a cohort of 316,799 individuals from the Copenhagen School Health Records Register (CSHRR), we examined whether BMI at ages 7 through 13 years was associated with later IBD. Linking the CSHRR to the Danish National Patient Register, we identified cases of Crohn's disease (CD) and ulcerative colitis (UC) diagnosed during follow-up. Cox regression was used to estimate the hazard ratios (HR) with 95% confidence intervals. RESULTS: During 10 million person-years of follow-up, 1500 individuals were diagnosed with CD and 2732 with UC. At all examined ages, a 1 unit increase in BMI z-score was associated with a significantly decreased risk of UC (HRs = 0.9) and with a significantly increased risk of CD when diagnosed before age 30 (HRs = 1.2). We observed no associations between changes in BMI z-score between 7 and 13 years and later risk of CD or UC. CONCLUSION: We found a direct association between childhood BMI and CD diagnosed before 30 years of age, and an inverse association between childhood BMI and UC irrespective of age. Our results support the previous hypotheses of obesity being a risk factor for CD, and suggest that childhood underweight might be a risk factor for UC.

Sources and determinants of vitamin D intake in Danish pregnant women.

Vitamin D deficiency during pregnancy has been associated with the development of several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes mellitus, preterm delivery, low birth weight, birth length, and bone mineral content. The aims of the present study were to estimate the intake and sources of vitamin D in Danish pregnant women and to examine potential determinants of vitamin D intake of the recommended level (10 µg per day). In 68,447 Danish pregnant women the mean ± SD for vitamin D intake was 9.23 ± 5.60 µg per day (diet: 3.56 ± 2.05 µg per day, supplements: 5.67 ± 5.20 µg per day). 67.6% of the women reported use of vitamin D supplements but only 36.9% reported use of vitamin D supplements of at least 10 µg. Supplements were the primary source of vitamin D for the two higher quartiles of total vitamin D intake, with diet being the primary source for the two lower quartiles. Determinants of sufficient total vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose that clinicians encourage vitamin D supplementation among pregnant women, with special focus on vulnerable groups such as the young, smokers and multiparous women, in order to improve maternal and fetal health both during and after pregnancy.