Early thiopurine maintenance is associated with reduced proximal disease progression and colectomy rate in ulcerative colitis.

BACKGROUND: Thiopurines effectively maintain remission in ulcerative colitis patients. Whether early initiation of thiopurines after ulcerative colitis diagnosis decreases proximal disease progression and colectomy rates is not known. METHODS: We conducted a cohort study of ulcerative colitis subjects recruited from 1970 to 2009. Early thiopurine maintenance was defined as commencement of azathioprine or mercaptopurine within 5 years of diagnosis and maintenance for at least 6 months. Propensity score matching was conducted to correct for confounders influencing early thiopurine introduction. Outcomes of interest were colectomy rate and endoscopic proximal disease extension. RESULTS: 982 consecutive ulcerative colitis subjects (12 879 patient-years) were recruited with 116 requiring colectomy. Thiopurines initiation and maintenance increased over time with median time to thiopurine commencement decreasing from 23 years in the first decade to 2 years in the last decade (P < 0.0001). Multivariate analysis showed that early thiopurine maintenance significantly decreased the need for colectomy [hazard ratio, 0.13; 95% confidence interval (CI):0.03-0.55; P = 0.006]. The number of subjects needed to be treated to reduce one colectomy at 5 and 10 years was 18 (95% CI, 16- 36) and 12 (95% CI, 11-25). After propensity score matching, early thiopurine maintenance was significantly associated with decreased colectomy (hazard ratio, 0.10; 95% CI, 0.03-0.43; P = 0.002) and proximal progression of disease extent (hazard ratio, 0.26; 95% CI, 0.10-0.78; P = 0.015). CONCLUSION: Early thiopurine maintenance for >6 months is significantly associated with reduced colectomy and proximal progression of disease extent in ulcerative colitis.

High prevalence of Crohn disease and ulcerative colitis among older people in Sydney.

OBJECTIVES: To determine the age-standardised prevalence of inflammatory bowel disease (IBD) in a metropolitan area of Sydney, with a focus on its prevalence among older people. DESIGN, SETTING: Population-based epidemiological study of people with IBD in the City of Canada Bay, a local government area in the inner west of Sydney, during 1 March 2016 - 10 November 2016. PARTICIPANTS: Patients diagnosed with confirmed IBD according to the Copenhagen or revised Porto criteria. MAIN OUTCOME MEASURES: Crude prevalence of IBD, including Crohn disease and ulcerative colitis; age-standardised prevalence of IBD, based on the World Health Organization standard population; prevalence rates among people aged 65 years or more. RESULTS: The median age of 364 people with IBD was 47 years (IQR, 34-62 years); 185 were women (50.8%). The crude IBD prevalence rate was 414 cases (95% CI, 371-456 cases) per 100 000 population; the age-standardised rate was 348 cases (95% CI, 312-385 cases) per 100 000 population. The age-standardised rate for Crohn disease was 166 cases (95% CI, 141-192 cases) per 100 000 population; for ulcerative colitis, 148 cases (95% CI, 124-171 cases) per 100 000 population. The IBD prevalence rate in people aged 65 years or more was 612 cases (95% CI, 564-660 cases) per 100 000, and for those aged 85 years or more, 891 cases (95% CI, 833-949 cases) per 100 000; for people under 65, the rate was 380 cases (95% CI, 342-418 cases) per 100 000. CONCLUSIONS: We found that the prevalence of confirmed IBD in a metropolitan sample was highest among older people. Challenges for managing older patients with IBD include higher rates of comorbid conditions, polypharmacy, and cognitive decline, and the immunosuppressive nature of standard therapies for IBD.

Comorbidities Rather Than Age Are Associated With the Use of Immunomodulators in Elderly-onset Inflammatory Bowel Disease.

BACKGROUND AND AIM: The use of immunomodulators (IMs) is often avoided in elderly patients with inflammatory bowel disease (IBD) due to concerns about complications. Our aim is to compare the use of IMs in elderly and younger patients with Crohn's disease (CD) or ulcerative colitis (UC) and identify markers that predict their use. METHODS: In this retrospective cohort study, patients diagnosed with IBD from 1970 to 2009 were recruited from the "Sydney IBD Cohort." Patients diagnosed at age 60 years old or older and between 16 and old 40 years were classified as "elderly-onset" and "young-onset" respectively. RESULTS: A total of 255 elderly-onset patients (115 CD, 140 UC) and 1244 young-onset patients (657 CD, 587 UC) were recruited. Most elderly-onset patients had colonic CD (61.4%), whereas young-onset patients had predominantly ileocolonic CD (42.8%, P < 0.0001). Left-sided UC was the most common disease localization for both elderly-onset (52.1%) and young-onset patients (42.2%, P = 0.013). The cumulative probability of IM exposure at 5 years post-diagnosis was significantly less in elderly-onset patients compared with young-onset patients for CD (20.0% vs 33.4%, P = 0.0002) and UC (7.8% vs 13.4%, P = 0.0007). Age at diagnosis was not associated with the time to IMs introduction. Charlson Comorbidity Index was shown to delay IM introduction in CD (hazard ratio [HR] 0.863; 95% CI, 0.787-0.946; P = 0.002) and UC (HR 0.807; 95% CI, 0.711-0.917; P = 0.001). Early IM use was associated with reduced need for abdominal and perianal surgery in CD (HR 0.177; 95% CI, 0.089-0.351; P < 0.0001). CONCLUSIONS: Comorbidity and not age at diagnosis is associated with IM introduction. Early IM is associated with reduced surgery in both young- and elderly-onset CD but not UC.

Inflammatory Bowel Disease Environmental Risk Factors: A Population-Based Case-Control Study of Middle Eastern Migration to Australia.

BACKGROUND & AIMS: The incidences of the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC) are increasing, indicating gene-environment interactions. Migrants from low-IBD-prevalence countries to a high-prevalence country may help identify the relative contribution of environmental risk factors compared with native Caucasians. METHODS: This prospective case-control study evaluated IBD environmental risk factors of Middle Eastern migrants (MEM) in Australia compared with matched Caucasian IBD subjects, MEM controls, Caucasian controls, and controls in the Middle East using adjusted odds ratios (aOR). RESULTS: A total of 795 subjects were recruited: 154 MEM cases (75 CD; 79 UC), 153 MEM controls, 162 Caucasian cases (85 CD; 77 UC), 173 Caucasian controls, and 153 controls in Lebanon. Smoking increased CD risk in MEM and Caucasians and reduced UC risk in Caucasians (aOR, 0.77; 95% CI, 0.41-0.98) but not MEM (aOR, 1.45; 95% CI, 0.80-2.62). Antibiotic use reduced the risk of MEM CD (aOR, 0.27; 95% CI, 0.11-0.67) and UC (aOR, 0.38; 95% CI, 0.18-0.80), but increased the risk in Caucasians (CD: aOR, 5.24; 95% CI, 2.13-12.90; and UC: aOR, 6.82; 95% CI, 2.67-17.38). Most hygiene markers (rural dwelling, pet ownership, pet feeding, and farm animal contact) reduced CD and UC risk in MEM (P < .05). In contrast, in Caucasians these hygiene markers lacked significance. Other significant risk factors include IBD family history, appendectomy, tonsillectomy, and breastfeeding. CONCLUSIONS: Differential IBD environmental risk factors exist between migrants and native Caucasians, indicating a dynamic interplay between environmental factors and IBD risk for immigrants that is distinct to those factors most relevant in native Caucasians.

Early use of thiopurines or methotrexate reduces major abdominal and perianal surgery in Crohn's disease.

BACKGROUND: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial. METHODS: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months. Propensity score matching was conducted to correct for confounders influencing early IM introduction. Outcomes of interest were rates of initial and recurrent major abdominal surgery for CD and their predictive factors. RESULTS: A total of 1035 consecutive patients with CD (13,061 patient-years) were recruited. The risk of first and recurrent major abdominal surgery at 1, 5, and 10 years were 17.5%, 28.4%, and 39.5% and 5.9%, 19.0%, and 33.3%, respectively. Early IM use increased over time from 1.3% to 55.3% (P < 0.0001) and was a significant independent predictor of lower rates of initial abdominal surgery (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.35-0.69), recurrent abdominal surgery (HR, 0.44; 95% CI, 0.25-0.79) and perianal surgery (HR, 0.30; 95% CI, 0.16-0.56). Using propensity score matching, early IM significantly reduced surgical rates (HR, 0.54; 95% CI, 0.37-0.79). Number needed to treat to prevent a surgical event at 5 years from diagnosis and after initial surgery was 6.99 (95% CI, 5.34-11.95) and 8.59 (95% CI, 6.26-23.93), respectively. CONCLUSIONS: Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.

Modifiable factors associated with nonadherence to maintenance medication for inflammatory bowel disease.

BACKGROUND: Poor adherence frequently impaired the efficacy of therapy to maintain remission from inflammatory bowel diseases (IBD). There is a lack of practical and effective interventions to improve adherence. This study aimed to identify modifiable risk factors, which may yield targets for new interventions. METHODS: Participants with IBD were recruited from hospital outpatient clinics and office-based gastroenterologists. Demographic and disease-related data were recorded by means of self-administered questionnaires. Modifiable risk factors were assessed with the validated Belief about Medicine Questionnaire, Hospital Anxiety and Depression Score, and short inflammatory bowel disease questionnaire. Adherence was assessed separately for 5-aminosalicylates, thiopurines, and biological agents using the validated Medicine Adherence Report Scale (good adherence defined as >16). RESULTS: Nonadherence occurred in 102 of 356 participants (28.7%). Adherence increased significantly with more aggressive therapies (median Medicine Adherence Report Scale: 5-aminosalicylates 18, thiopurines 19, biological 20; P < 0.0001). Nonadherence was not associated with anxiety and depression or disease-related patient knowledge. Adherent patients had significantly higher belief of necessity for medication (P < 0.0001) and a trend toward lower concerns about medication (P = 0.08). Membership of an IBD patient organization was associated with better adherence (P < 0.0001). Concerns about medication rose significantly with more aggressive therapies (P = 0.009), but belief of necessity was similar for all medications. CONCLUSIONS: Nonadherence occurs most frequently with 5-aminosalicylates. Belief of necessity may prove the key target for future interventions, although general IBD education is unlikely to yield an adherence benefit. Patient organization membership should be encouraged.

Conveying medication benefits to ulcerative colitis patients and effects on patient attitudes regarding thresholds for adherence.

BACKGROUND AND AIM: Adherence to medication that maintains remission by patients with ulcerative colitis (UC) is poor but little is known regarding patients' perception of medication benefit that may enhance adherence rates. The aims were to study patients' understanding and preference on methods of conveying statistical information and to study indicated thresholds for adherence to medication for UC. METHODS: Four methods of displaying information on benefits of maintenance therapy were explained to patients with UC in remission: relative risk reduction [RR], absolute risk reduction [AR], number needed to treat [NNT] and optical representation via Cates plot [CP]. Patients' understanding and preference for each method were evaluated. Participants were asked to state minimum thresholds relating to relapse prevention and colorectal cancer risk reduction that they would require in order for them to adhere to medication for UC. RESULTS: Of 50 participants, 48% preferred data presentation by RR over CP (28%), AR (20%) and NNT (4%). 94% found RR easy to understand, better than AR (88%), CP (74%), or NNT (48%). For bowel cancer prevention, 94% indicated adherence for benefit levels of 61% RR but only 57% for the corresponding CP (P<0.001). For relapse prevention, 78% of patients indicated adherence for benefit levels of 40% RR but only 43% for the corresponding CP (P<0.001). CONCLUSION: Patients with UC prefer data presented by RR, and apply significantly higher thresholds for adherence when presented with CP compared to RR. Reduction of cancer risk may be a stronger motivator than maintenance of remission.

Inflammatory bowel disease and pregnancy: lack of knowledge is associated with negative views.

BACKGROUND: Enabling women with inflammatory bowel diseases (IBD) to have successful pregnancies requires complex decisions. The study aimed to assess patients' views on IBD and pregnancy and to evaluate any association with subject knowledge. METHODS: General attitudes of females with IBD were assessed on fertility, medication use, delivery mode and pregnancy outcomes. Attitudes regarding personal situation were assessed in participants nulliparous since IBD diagnosis. Knowledge of pregnancy-related issues in IBD was assessed by the Crohn's and Colitis Pregnancy Knowledge Score 'CCPKnow'. RESULTS: Of 145 participants 68% of participants agreed with need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms. 36% believed that all IBD medication is harmful to unborn children. Of 96 women nulliparous after IBD diagnosis, 46% were worried about infertility, 75% expressed concern about passing IBD to offspring and 30% considered not having children. Nearly all participants worried about the effects of IBD on pregnancy and the effects of pregnancy on IBD. General attitudes that 'medication should be stopped prior to conception' (P<0.001), 'pregnant women should avoid all IBD drugs' (P<0.001), and 'put up with symptoms' (P<0.001) were associated with significantly lower CCPKnow scores. CONCLUSION: Over a third of patients considered IBD medication harmful to unborn children. Fear of infertility and concerns about inheritance may explain high rates of voluntary childlessness. Attitudes contrary to medical evidence were associated with significantly lower knowledge. Young women with IBD, particularly those with poor knowledge, should be offered education and counselling about pregnancy-related issues.

Better disease specific patient knowledge is associated with greater anxiety in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD)-related knowledge not only empowers patients, but may also engender anxiety. The study aimed to identify predictors of anxiety in IBD and examine the interplay between anxiety and disease-related patient knowledge. The effect of anxiety on quality of life was also explored. METHODS: Ambulatory IBD patients provided data on demographics, their IBD and Crohn's Colitis Association (CCA) membership status. Disease-related knowledge was assessed using the validated Crohn's and Colitis Knowledge score (CCKnow) and disease related QOL using the short IBD questionnaire (SIBDQ). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scores. RESULTS: Of the 258 patients 19.4% had a potential anxiety and a further 22.4% had a probable anxiety disorder. Females (P=0.003), tertiary care patients (P=0.014) and non-Caucasian patients (P=0.037) had significantly higher anxiety levels. CCA members had marginally higher levels of anxiety (P=0.07). Anxiety was associated with significantly better patient knowledge (P=0.016) and increased depression (P<0.001). Disease related quality of life was significantly lower in patients with anxiety (P<0.001). CONCLUSIONS: This is the first study to demonstrate that better patient knowledge is associated with higher anxiety levels. The reason for this is unclear: educating patients about their disease might trigger anxiety, but, equally, anxious patients might seek out information and hence have better knowledge. It is thus noteworthy that an educational intervention may not necessarily reduce anxiety. Further work is needed to evaluate the association between anxiety and knowledge and to develop targeted interventions that will improve knowledge and simultaneously reduce anxiety.