Adherence to 5-aminosalicylic acid maintenance treatment in young people with ulcerative colitis: a retrospective cohort study in primary care

BACKGROUND: Maintenance treatment with 5-aminosalicylic acid (5-ASA) is recommended in ulcerative colitis (UC), but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking. AIM: To determine rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults 1 year following diagnosis of UC. DESIGN AND SETTING: Observational cohort study using the UK Clinical Practice Research Datalink among adolescents and young adults (aged 10-24 years) diagnosed with UC between 1 January 1998 and 1 May 2016. METHOD: Time to oral 5-ASA discontinuation (days) and adherence rates (proportion of days covered) were calculated during the first year of treatment using Kaplan-Meier survival analysis. Cox regression models were built to estimate the impact of sociodemographic and health-related risk factors. RESULTS: Among 607 adolescents and young adults starting oral 5-ASA maintenance treatment, one-quarter (n = 152) discontinued within 1 month and two- thirds (n = 419) within 1 year. Discontinuation was higher among those aged 18-24 years (74%) than younger age groups (61% and 56% in those aged 10-14 and 15-17 years, respectively). Adherence was lower among young adults than adolescents (69% in those aged 18-24 years versus 80% in those aged 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] = 1.10 to 1.92). Early corticosteroid use for an acute flare lowered the likelihood of oral 5-ASA discontinuation (aHR 0.68, 95% CI = 0.51 to 0.90). CONCLUSION: The first year of starting long-term therapies in adolescents and young adults diagnosed with UC is a critical window for active follow-up of maintenance treatment, particularly in those aged 18-24 years and those living in deprived postcodes

Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study.

OBJECTIVE: Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. DESIGN: We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. RESULTS: We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). CONCLUSIONS: Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD

Antidepressant medication use in Inflammatory Bowel Disease: a nationally representative population-based study.

BACKGROUND: Despite high rates of depression and anxiety, little is known about the use of antidepressants amongst individuals diagnosed with inflammatory bowel disease (IBD). AIMS: To evaluate temporal trends in the use of antidepressants; rates of antidepressant initiation and adherence of antidepressant use to international guidelines amongst individuals with IBD. METHODS: This is a study of 14,525 incident IBD cases from 2004 to 2016 compared with 58,027 controls matched 1:4 for age and sex from the Clinical Practice Research Datalink. After excluding tricyclic antidepressants, we performed a Cox regression analysis to determine the risk associated with antidepressant use and logistic regression analysis to determine risk associated with antidepressant undertreatment. RESULTS: Antidepressant use amongst individuals with IBD increased by 51% during the 12-year study period, who were 34% more likely to initiate antidepressants in the year after IBD diagnosis compared with controls (aHR:1.34, 95% CI 1.21-1.49). In those with IBD starting antidepressants, 67% received treatment lasting less than the duration recommended in international guidelines, of which 34% were treated for 1 month or less. 18-24 year olds were twice as likely to discontinue treatment within 1 month compared with those aged 40-60 years (aHR:2.03, 95% CI 1.40-2.95). Socioeconomic deprivation was also associated with early treatment discontinuation (aHR:1.40, 95% CI 1.07-1.83). CONCLUSIONS: In the year following IBD diagnosis individuals are significantly more likely to start antidepressants compared with controls, but treatment duration fell short of recommendations in the majority. Better integration of services may benefit individuals with IBD and psychiatric comorbidity

Systematic review with meta-analysis: Time to diagnosis and the impact of delayed diagnosis on clinical outcomes in inflammatory bowel disease.

BACKGROUND: The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain. AIM: To perform a systematic review of time to diagnosis and the impact of delayed diagnosis on clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We searched EMBASE and Medline from inception to 30th November 2022 for studies reporting diagnostic interval, from symptom onset to IBD diagnosis. We calculated the median, interquartile range (IQR) and pooled weighted median, of median diagnostic intervals of eligible studies. We defined delayed diagnosis as individuals above the 75th centile of longest time to diagnosis in each study. Using random effects meta-analysis, we pooled odds ratios (ORs) with 95% confidence intervals (CI) for studies reporting clinical outcomes, according to delayed diagnosis. RESULTS: One hunderd and one studies representing 112,194 patients with IBD (CD = 59,359; UC = 52,835) met inclusion criteria. The median of median times to diagnosis was 8.0 (IQR: 5.0-15.2) and 3.7 months (IQR: 2.0-6.7) in CD and UC, respectively. In high-income countries, this was 6.2 (IQR: 5.0-12.3) and 3.2 months (IQR: 2.2-5.3), compared with 11.7 (IQR: 8.3-18.0) and 7.8 months (IQR: 5.2-21.8) in low-middle-income, countries, for CD and UC respectively. The pooled weighted median was 7.0 (95% CI: 3.0-26.4) and 4.6 (95% CI: 1.0-96.0) months, for CD and UC respectively. Eleven studies, representing 6164 patients (CD = 4858; UC = 1306), were included in the meta-analysis that examined the impact of diagnostic delay on clinical outcomes. In CD, delayed diagnosis was associated with higher odds of stricturing (OR = 1.88; CI: 1.35-2.62), penetrating disease (OR = 1.64; CI: 1.21-2.20) and intestinal surgery (OR = 2.24; CI: 1.57-3.19). In UC, delayed diagnosis was associated with higher odds of colectomy (OR = 4.13; CI: 1.04-16.40). CONCLUSION: Delayed diagnosis is associated with disease progression in CD, and intestinal surgery in both CD and UC. Strategies are needed to achieve earlier diagnosis of IBD

Discontinuation and adherence to oral 5-aminosalicylic-acid maintenance treatment in adolescents and young adults with ulcerative colitis: a retrospective cohort study in primary care

Background:-Maintenance treatment with 5-aminosalicylic-acid (5-ASA) is recommended in ulcerative colitis, but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking. Aim:-We aimed to determine rates and risk factors for discontinuation and adherence to oral 5-aminosalicylic-acid in adolescents and young adults aged 10-24-years in their first-year following diagnosis of ulcerative colitis. Design and setting:-Observational cohort study using the UK Clinical Practice Research Datalink amongst adolescents and young adults (aged 10-24 years) diagnosed with ulcerative colitis between 1.1.1998-1.5.2016. Methods:-We calculated time to oral 5-aminosalicylic-acid discontinuation (days) and adherence rates (proportion of days covered) during the first year of treatment using Kaplan Meier survival analysis and built Cox regression models to estimate the impact of sociodemographic and health-related risk factors. Results:-Among 607 adolescents and young adults aged 10-24 years starting oral 5-aminosalicylic-acid maintenance treatment, a quarter discontinued after one month, and 69% within a year. Discontinuation was higher among those aged 18-24 years (74%) than younger groups (61%, 56%, in 10-14, and 15-17-years respectively). Adherence was lower among those young adults than adolescents (69% for ages 18-24 vs 80% ages 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio:1.46,-95%-CI:1.10-1.92). Early corticosteroid use for an acute flare, lowered the likelihood of oral 5-aminosalicylic-acid discontinuation (aHR:0.68, 95%-CI:0.51-0.90). Conclusion:-The first year of starting long term therapies in adolescents and young adults diagnosed with ulcerative colitis is a critical window for active follow up of maintenance treatment, particularly 18-24-year-olds and those living in deprived postcodes

Stoma Formation in Crohn's Disease and the Likelihood of Antidepressant Use: A Population-Based Cohort Study

BACKGROUND & AIMS: The impact of a temporary or permanent stoma on mental health in Crohn's Disease (CD) is unknown. The aim was to examine the association between intestinal surgery and stoma formation and subsequent antidepressant medication (ADM) use. METHODS: Using the Clinical Practice Research Datalink, we identified individuals with CD who underwent intestinal surgery between 1998-2018. We excluded individuals with a prescription for an ADM in the 6 months before surgery. Individuals were stratified into three groups: no stoma, temporary stoma, and permanent stoma. We used Kaplan-Meier curves to examine initiation of ADM after intestinal surgery and Cox regression to identify risk factors for ADM use after intestinal surgery. RESULTS: We identified 1,272 cases of CD undergoing their first intestinal surgery. Of these, 871 (68.5%) had no stoma, 191 (15.0%) had a temporary stoma and 210 (16.5%) had a permanent stoma. The 10-year cumulative incidence of ADM use was 26.4%, 33.4% and 37.3% respectively. Individuals with a permanent stoma were 71% more likely to receive an ADM than those with no stoma (HR 1.71, 95% CI 1.20-2.44). Individuals with a temporary stoma reversed within 12 months had a similar likelihood of ADM use to those without stoma formation (HR 0.99, 95% CI 0.64-1.53) whereas temporary stoma formation with late reversal after 12 months was associated with significantly greater likelihood of ADM use (HR 1.85, 95% CI 1.15-2.96). CONCLUSIONS: Permanent stomas and temporary stomas with late reversal surgery are associated with increased ADM use after intestinal surgery, likely associated with increased anxiety and depression

Antidepressant medication use in Inflammatory Bowel Disease: a nationally representative population-based study

Background Despite high rates of depression and anxiety, little is known about the use of antidepressants amongst individuals diagnosed with inflammatory bowel disease (IBD). Aims To evaluate temporal trends in the use of antidepressants; rates of antidepressant initiation and adherence of antidepressant use to international guidelines amongst individuals with IBD. Methods This is a study of 14,525 incident IBD cases from 2004 to 2016 compared with 58,027 controls matched 1:4 for age and sex from the Clinical Practice Research Datalink. After excluding tricyclic antidepressants, we performed a Cox regression analysis to determine the risk associated with antidepressant use and logistic regression analysis to determine risk associated with antidepressant undertreatment. Results Antidepressant use amongst individuals with IBD increased by 51% during the 12-year study period, who were 34% more likely to initiate antidepressants in the year after IBD diagnosis compared with controls (aHR:1.34, 95% CI 1.21-1.49). In those with IBD starting antidepressants, 67% received treatment lasting less than the duration recommended in international guidelines, of which 34% were treated for 1 month or less. 18-24 year olds were twice as likely to discontinue treatment within 1 month compared with those aged 40-60 years (aHR:2.03, 95% CI 1.40-2.95). Socioeconomic deprivation was also associated with early treatment discontinuation (aHR:1.40, 95% CI 1.07-1.83). Conclusions In the year following IBD diagnosis individuals are significantly more likely to start antidepressants compared with controls, but treatment duration fell short of recommendations in the majority. Better integration of services may benefit individuals with IBD and psychiatric comorbidity

Prevalence and duration of gastrointestinal symptoms before diagnosis of Inflammatory Bowel Disease and predictors of timely specialist review: a population-based study

Background and Aims Lack of timely referral and significant waits for specialist review amongst individuals with unresolved gastrointestinal (GI) symptoms can result in delayed diagnosis of Inflammatory Bowel Disease (IBD). Aims To determine the frequency and duration of GI symptoms and predictors of timely specialist review before the diagnosis of both Crohn’s Disease (CD) and ulcerative colitis (UC). Methods Case-control study of IBD matched 1:4 for age and sex to controls without IBD using the Clinical Practice Research Datalink from 1998-2016. Results We identified 19,555 cases of IBD, and 78,114 controls. 1 in 4 cases of IBD reported gastrointestinal symptoms to their primary care physician more than 6 months before receiving a diagnosis. There is a significant excess prevalence of GI symptoms in each of the 10 years before IBD diagnosis. GI symptoms were reported by 9.6% and 10.4% at 5 years before CD and UC diagnosis respectively compared to 5.8% of controls. Amongst patients later diagnosed with IBD, <50% received specialist review within 18 months from presenting with chronic GI symptoms. Patients with a previous diagnosis of irritable bowel syndrome or depression were less likely to receive timely specialist review (IBS: HR=0.77, 95%CI 0.60-0.99, depression: HR=0.77, 95%CI 0.60-0.98). Conclusions There is an excess of GI symptoms 5 years before diagnosis of IBD compared to the background population which are likely attributable to undiagnosed disease. Previous diagnoses of IBS and depression are associated with delays in specialist review. Enhanced pathways are needed to accelerate specialist referral and timely IBD diagnosis

Stoma formation in Crohn's Disease and the likelihood of antidepressant use: a population-based cohort study.

BACKGROUND AND AIMS: The impact of a temporary or permanent stoma on mental health in Crohn's Disease (CD) is unknown. AIM: To examine the association between intestinal surgery and stoma formation and subsequent antidepressant medication (ADM) use. METHODS: Using the Clinical Practice Research Datalink, we identified individuals with CD who underwent intestinal surgery between 1998-2018. We excluded individuals with a prescription for an ADM in the 6 months before surgery. Individuals were stratified into three groups: no stoma, temporary stoma, and permanent stoma. We used Kaplan-Meier curves to examine initiation of ADM after intestinal surgery and Cox regression to identify risk factors for ADM use after intestinal surgery. RESULTS: We identified 1,272 cases of CD undergoing their first intestinal surgery. Of these, 871 (68.5%) had no stoma, 191 (15.0%) had a temporary stoma and 210 (16.5%) had a permanent stoma. The 10-year cumulative incidence of ADM use was 26.4%, 33.4% and 37.3% respectively. Individuals with a permanent stoma were 71% more likely to receive an ADM than those with no stoma (HR 1.71, 95% CI 1.20-2.44). Individuals with a temporary stoma reversed within 12 months had a similar likelihood of ADM use to those without stoma formation (HR 0.99, 95% CI 0.64-1.53) whereas temporary stoma formation with late reversal after 12 months was associated with significantly greater likelihood of ADM use (HR 1.85, 95% CI 1.15-2.96). CONCLUSION: Permanent stomas and temporary stomas with late reversal surgery are associated with increased ADM use after intestinal surgery, likely associated with increased anxiety and depression