Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN).

BACKGROUND AND OBJECTIVES: Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. METHODS: We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. RESULTS: A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P  < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. CONCLUSION: PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.

Perianal Crohn's Disease Is Associated With Poor Disease Outcome: A Nationwide Study From the epiIIRN Cohort.

BACKGROUND & AIMS: Limited population-based data have explored perianal involvement in Crohn's disease (CD) and compared the disease course between severe and non-severe perianal CD (PCD). We aimed to explore the disease course of these phenotypes in a population-based study of CD. METHODS: Cases were identified from the epi-IIRN cohort and included 2 Israeli health maintenance organizations covering 78% of the population. We validated specific algorithms to identify fistulizing PCD and to differentiate severe from non-severe disease by medication utilization, International Classification of Disease, 9th Revision codes, and perianal procedures. RESULTS: A total of 12,904 CD patients were included in an inception cohort from 2005 (2186 pediatric-onset, 17%) providing 86,119 person-years of follow-up. Fistulizing PCD was diagnosed in 1530 patients (12%) (574 with severe PCD, 4%). The prevalence of PCD was 7.9%, 9.4%, 10.3%, and 11.6% at 1, 3, 5, and 10 years from CD diagnosis, respectively. At 5 years, PCD patients were more likely to be hospitalized (36% in non-PCD vs 64% in PCD; P < .001), undergo inflammatory bowel disease-related surgeries (9% vs 38%, respectively; P < .001), and develop anorectal cancer (1.2/10,000 person-years for non-PCD vs 4.2/10,000 for PCD; P = .01). Severe PCD was associated with poorer outcomes compared with non-severe PCD, as shown for hospitalizations (61% in non-severe PCD vs 73% in severe; P = .004) and surgeries (35% vs 43%; P = .001). CONCLUSIONS: Despite higher utilization of immunomodulators and biologics, PCD is associated with poor disease outcomes, especially in severe PCD.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN.

BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Pediatric-onset Inflammatory Bowel Disease Has Only a Modest Effect on Final Growth: A Report From the epi-IIRN.

OBJECTIVES: The impact of pediatric-onset inflammatory bowel disease (IBD) on growth is debated. We aimed to investigate the effect of IBD on anthropometric measures at young adulthood. METHODS: Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005-2019) were identified in a national database along with matched non-IBD controls. RESULTS: Overall, 2229 IBD cases (68% CD) were matched to 4338 controls. Only females with CD differed in final height from controls (z scores: -0.37 ±â€Š1.09 vs -0.25 ±â€Š1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ±â€Š0.2 cm (all females) and 1.2 ±â€Š0.3 cm in females diagnosed <14 years (P = 0.02). Final height was reduced in both sexes according to adjusted mean height difference analysis (-0.43 cm, 95% confidence interval -0.85 to -0.02; P = 0.04). This difference increased in patients with CD who underwent abdominal surgery (-0.91 cm, 95% confidence interval -1.39 to -0.42; P = 0.01). The proportion of patients with CD achieving final height z scores of -1 and zero differed significantly from controls for both males (71.1% and 34.8% vs 79.1% and 43.0%, respectively; P < 0.001) and females (67.7% and 30.4% vs 79.6%, and 43.3%, respectively; P < 0.001). Patients treated with anti-tumor necrosis factor agents during growth potential had similar height improvement to other regimens. Predominantly, patients with CD were leaner, with a greater proportion of subjects with underweight, compared with controls. CONCLUSIONS: In pediatric-onset IBD, absolute final height was modestly affected by females with CD. Nevertheless, greater proportions of both sexes with early diagnosis of CD failed to achieve normal final height, compared with controls.

Population-based cohort of 500 patients with Gaucher disease in Israel.

OBJECTIVE: To characterise a population-based cohort of patients with Gaucher disease (GD) in Israel relative to the general population and describe sociodemographic and clinical differences by disease severity (ie, enzyme replacement therapy [ERT] use). DESIGN: A cross-sectional study was conducted. SETTING: Data from the Clalit Health Services electronic health record (EHR) database were used. PARTICIPANTS: The study population included all patients in the Clalit EHR database identified as having GD as of 30 June 2014. RESULTS: A total of 500 patients with GD were identified and assessed. The majority were ≥18 years of age (90.6%), female (54.0%), Jewish (93.6%) and 34.8% had high socioeconomic status, compared with 19.0% in the general Clalit population. Over half of patients with GD with available data (51.0%) were overweight/obese and 63.5% had a Charlson Comorbidity Index ≥1, compared with 46.6% and 30.4%, respectively, in the general Clalit population. The majority of patients with GD had a history of anaemia (69.6%) or thrombocytopaenia (62.0%), 40.4% had a history of bone events and 22.2% had a history of cancer. Overall, 41.2% had received ERT. CONCLUSIONS: Establishing a population-based cohort of patients with GD is essential to understanding disease progression and management. In this study, we highlight the need for physicians to monitor patients with GD regardless of their ERT status.

Association between exposure to desalinated sea water and ischemic heart disease, diabetes mellitus and colorectal cancer; A population-based study in Israel.

BACKGROUND: Drinking water (DW) is an important dietary source of magnesium. Recently, Israel has increased its use of desalinated seawater (DSW) as DW country-wide. Its negligible magnesium content, however, raises concern that consumption of DSW may be associated with hypomagnesemia and increase the risk of ischemic heart disease (IHD), diabetes mellitus (DM), and colorectal cancer (CRC). OBJECTIVES: We tested whether there was a change in incidence of negative health outcomes (IHD, DM, and CRC) following the introduction of DSW supply in a population-based ecologic study in Israel. METHODS: A historical prospective analysis was applied to members aged 25-76 during 2004-2013 of Clalit Health Services (Clalit), the largest healthcare provider in Israel, using its electronic medical record database. Multivariable analyses were adjusted for age, sex, socioeconomic status, smoking status, and body mass index. RESULTS: An increased odds ratio was found for IHD (0.96, 95% CI 0.93-0.99 at baseline and 1.06, 95% CI 1.02-1.11 at the end of the follow-up period), but no time trend was observed. CONCLUSIONS: We found that the risk for IHD increased during the study period. The risks for DM and CRC were unchanged. Long term studies are needed for assessing the risk for CRC due to the long latency. The higher risk for IHD has practical public health implications and raise the need to add magnesium to DSW.