The effect of arthropathies on illness perceptions, coping strategies, outcomes, and their changes over time in patients with inflammatory bowel disease: a 12-month follow-up study.

OBJECTIVES: Arthropathies are a common extraintestinal manifestation (EIM) in inflammatory bowel disease (IBD). This study evaluated the differences in illness perceptions, coping strategies, and illness outcomes between patients with IBD with and without arthropathies at baseline and examined changes at 12 months in these variables in patients with arthropathies. METHODS: In total, 204 patients with (n=123) and without (n=81) arthropathies completed questionnaires at baseline and after 1 year, assessing illness perceptions, coping strategies, quality of life, and work and activity impairment. A linear regression analysis assessed the effect of arthropathies on these factors compared with patients without arthropathies. A mixed model analysis evaluated changes in illness perceptions, coping strategies, and outcomes in patients with arthropathies over time. RESULTS: Patients with arthropathies had more persistent thoughts on symptomatology and the variability of symptoms, held more negative views on the effects of illness, had heightened emotions that affected daily functioning, and had a poorer understanding of IBD than patients without arthropathies. Patients with arthropathies could more efficiently divert attention, felt more useful to others, and perceived a reduced physical and mental health and an increased activity impairment compared with patients without arthropathies. At follow-up, patients with arthropathies were more sceptical about the effectiveness of medical treatment but were better able to adapt their activities to their complaints compared with baseline. CONCLUSION: Patients with arthropathies in IBD adopt different illness perceptions and coping strategies and have different outcomes compared with patients without arthropathies, which is important to know when designing behavioral and physical interventions to improve functioning.

Clinical Predictors of Future Nonadherence in Inflammatory Bowel Disease.

BACKGROUND: Nonadherence to medical therapy is frequently encountered in patients with inflammatory bowel disease (IBD). We aimed to identify predictors for future (non)adherence in IBD. METHODS: We conducted a multicenter prospective cohort study with adult patients with Crohn's disease (CD) and ulcerative colitis (UC). Data were collected by means of 3-monthly questionnaires on the course of disease and healthcare utilization. Medication adherence was assessed using a visual analogue scale, ranging from 0% to 100%. Levels <80% were considered to indicate nonadherence. The Brief Illness Perception Questionnaire was used to identify illness perceptions. We used a logistic regression analysis to identify patient- and disease-related factors predictive of nonadherence 3 months after the assessment of predictors. RESULTS: In total, 1558 patients with CD and 1054 patients with UC were included and followed for 2.5 years. On average, 12.1% of patients with CD and 13.3% of patients with UC using IBD-specific medication were nonadherent. Nonadherence was most frequently observed in patients using mesalazine (CD), budesonide (UC) and rectally administrated therapy (both CD and UC). A higher perceived treatment control and understanding of the disease were associated with adherence to medical therapy. Independent predictors of future nonadherence were age at diagnosis (odds ratio [OR]: 0.99 per year), nonadherence (OR: 26.91), a current flare (OR: 1.30) and feelings of anxiety/depression (OR: 1.17), together with an area under the receiver-operating-characteristics curve of 0.74. CONCLUSIONS: Lower age at diagnosis, flares, feelings of anxiety or depression, and nonadherence are associated with future nonadherence in patients with IBD. Altering illness perceptions could be an approach to improve adherence behavior.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up.

BACKGROUND: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. METHODS AND FINDINGS: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). CONCLUSIONS: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Non-adherence to Anti-TNF Therapy is Associated with Illness Perceptions and Clinical Outcomes in Outpatients with Inflammatory Bowel Disease: Results from a Prospective Multicentre Study.

BACKGROUND AND AIMS: Non-adherence to anti-tumour necrosis factor [TNF] agents in patients with inflammatory bowel disease [IBD] is a serious problem. In this study, we assessed risk factors for non-adherence and examined the association between adherence to anti-TNF agents and loss of response [LOR]. METHODS: In this multicentre, 12-month observational study, outpatients with IBD were included. Demographic and clinical characteristics were recorded. Adherence was measured with the Modified Morisky Adherence Scale-8 [MMAS-8] and 12-month pharmacy refills [medication possession ratio, MPR]. Risk factors included demographic and clinical characteristics, medication beliefs, and illness perceptions. Cox regression analysis was performed to determine the association between MPR and LOR to anti-TNF, IBD-related surgery or hospitalisation, dose intensification, or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included [67 infliximab, 61 adalimumab], mean age 37 ( ± standard deviation [SD] 14) years, 71 [56%] female. Median disease duration was 8 (interquartile range [IQR] 4-14) years. Clinical disease activity was present in 41/128 [32%] patients, 36/127 [28%] patients had an MMAS-8 < 6 ['low adherence'], and 25/99 [25%] patients had an MPR < 80% [non-adherence]. Risk factors for non-adherence included adalimumab use (odds ratio [OR] 10.1, 95% confidence interval [CI] 2.62-40.00), stronger emotional response [OR 1.16, 95% CI 1.02-1.31], and shorter timeline perception, i.e. short perceived illness duration [OR 0.60, 95% CI 0.38-0.96]. Adherence is linearly and negatively [OR 0.14, 95% CI 0.03-0.63] associated with LOR. CONCLUSION: Non-adherence to anti-TNF agents is strongly associated with LOR to anti-TNF agents, adalimumab use, and illness perceptions. The latter may provide an important target for interventions aimed at improving adherence and health outcomes.

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.

Self-reported disability in patients with inflammatory bowel disease largely determined by disease activity and illness perceptions.

BACKGROUND: The inflammatory bowel disease (IBD) disability index has recently been introduced to measure patients' physical, psychological, familial, and social limitations associated with IBD. We assessed factors related to self-reported disability and the relationship between disability and direct health care costs. METHODS: A large cohort of patients with Crohn's disease (CD) and ulcerative colitis (UC) was prospectively followed for 2 years by 3 monthly web-based questionnaires. At 2 years, patients completed the IBD disability index, with lower score indicating more disability. Linear regression analysis was used to examine the impact of demographics, clinical characteristics, and illness perceptions on self-reported disability. Trends in direct health care costs across the disability severity groups minimal, mild, moderate, and severe, were tested. RESULTS: A total of 554 patients with CD and 424 patients with UC completed the IBD disability index (response rate, 45%). Both clinical characteristics and illness perceptions significantly contributed to self-reported disability (45%-47%, P = 0.000 and 8%-12%, P = 0.000, respectively). Patients with CD scored lower on the self-reported IBD disability index than patients with UC (0.255 versus 3.890, P < 0.000), indicating more disability in patients with CD. Factors independently associated with higher self-reported disability rates were increased disease activity, illness identity (higher number of symptoms attributed to IBD), and stronger emotional response. Disease duration and disease phenotype were not associated with self-reported disability. Direct health care costs increased with the worsening of self-reported disability (P = 0.000). CONCLUSIONS: More disability was reported by patients with CD than by UC. Self-reported disability in IBD was mainly determined by clinical disease activity and illness perceptions but not by disease duration or disease phenotype.

Back/joint pain, illness perceptions and coping are important predictors of quality of life and work productivity in patients with inflammatory bowel disease: a 12-month longitudinal study.

BACKGROUND AND AIMS: Back and joint pain are the most common extraintestinal symptoms reported by patients with inflammatory bowel disease (IBD). We assessed the impact of back/joint pain, illness perceptions, and coping on quality of life (QOL) and work productivity in patients with IBD. METHODS: Our cohort included 155 IBD patients with and 100 without arthropathy. Arthropathy was defined as daily back pain for ≥3 months and/or peripheral joint pain and/or joint swelling over the last year. At baseline and at 12 months, patients completed questionnaires on the extent of back/joint pain, IBD disease activity, illness perceptions, coping, QOL, and work productivity. The impact of back/joint pain, illness perceptions and coping on QOL and work productivity was determined, using linear mixed models. RESULTS: In total, 204 IBD patients (72% Crohn's disease, 40% male, mean age 44 ± 14 years) completed questionnaires at both time points. At both time points, IBD patients with back/joint pain reported a significantly lower QOL and work productivity compared with IBD patients without back/joint pain. Predictors of low QOL were back/joint pain (ß = -1.04, 95% confidence interval [CI] -1.40, -0.68), stronger beliefs about the illness consequences (ß = -0.39, 95% CI -0.59, -0.18) and emotional impact of IBD (ß = -0.47, 95% CI -0.66, -0.28), and the coping strategy 'decreasing activity' (ß = -0.26, 95% CI -0.48, -0.03). Predictors of work productivity were back/joint pain (ß = 0.22, 95% CI 0.07, 0.37) and illness consequences (ß = 0.14, 95% CI 0.06, 0.22). CONCLUSION: Back/joint pain, illness perceptions, and coping are significant predictors of QOL and work productivity, after controlling for disease activity.

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study.

BACKGROUND: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. AIMS: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. METHODS: A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. RESULTS: 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). CONCLUSIONS: Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions.

Effect of aging on healthcare costs of inflammatory bowel disease: a glimpse into the future.

BACKGROUND: Population aging is expected to result in a substantial additional burden on healthcare resources in the near future. We aimed to assess the current and future impact of aging on direct healthcare costs (DHC) attributed to inflammatory bowel disease (IBD). METHODS: Patients with IBD from a Dutch multicenter cohort filled out 3-monthly questionnaires for 2 years. Elderly (≥60 yr) and younger patients (18-60 yr) IBD were analyzed for differences in 3-monthly DHC, productivity losses, and out-of-pocket costs. Prevalence rates were obtained from a health insurance database. Estimates of annual DHC and prevalence rates were applied to the total Dutch adult population in 2011 and then projected to 2040, using predicted changes in population demography, prices, and volume. RESULTS: IBD-attributable DHC were lower in elderly than in younger patients with IBD with respect to 3-monthly DHC (&OV0556;359 versus &OV0556;978, P < 0.01), productivity losses (&OV0556;108 versus &OV0556;456, P < 0.01), and out-of-pocket costs (&OV0556;40 versus &OV0556;57, P < 0.01). Between 2011 and 2040, the percentage of elderly IBD patients in the Netherlands has been projected to rise from 24% to 35%. Between 2011 and 2040, DHC of the total IBD population in the Netherlands are projected to increase from &OV0556;161 to &OV0556;661 million. Population aging accounted for 1% of this increase, next to rising prices (29%), and volume growth (70%). CONCLUSIONS: Population aging has a negligible effect on IBD-attributable DHC of the IBD population in the near future, because the average costs incurred by elderly patients with IBD are considerably lower than those incurred by younger patients with IBD.

Determinants of health-related quality of life in Crohn's disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Understanding the determinants of Crohn's disease (CD) patients' health-related quality of life (HRQOL) may facilitate interventions that improve HRQOL. Therefore, we systematically assessed determinants of HRQOL in adult CD patients. METHODS: The databases PubMed, EMBASE, the Cochrane Library, PsycINFO and CINAHL were searched for English abstracts, related to socio-demographic, psychological, clinical and treatment-related determinants of HRQOL in CD disease. Two independent reviewers extracted study characteristics and assessed the methodological quality according the criteria of Hayden et al. The main outcome was the number of studies showing a statistically significant association between the above-mentioned determinants and HRQOL. A meta-analysis was performed to quantify the relationship between disease activity and HRQOL. RESULTS: Of the 2060 articles identified, 29 eligible studies were included. The majority of studies were cross-sectional and had a moderate to high quality. Data on psychological determinants were scarce. Work disability, increased disease activity, number of relapses, corticosteroid treatment and hospitalization rate were significantly associated with a lower HRQOL in the majority of included studies. Biological treatment positively influenced HRQOL. The pooled data on the association between disease activity and HRQOL resulted in a weighed mean correlation coefficient of -0.61 (CI -0.65 to -0.57). CONCLUSIONS: HRQOL of adult CD patients is consistently determined by markers of active disease, including work disability, increased disease activity, number of relapses, biological treatment and hospitalization rate. As disease activity contributed to only 37% of HRQOL, there remains a need for additional, possibly modifiable, determinants. These determinants may refine possibilities to improve HRQOL.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

BACKGROUND AND AIMS: Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. METHODS: We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Low rates of adherence for tumor necrosis factor-α inhibitors in Crohn's disease and rheumatoid arthritis: results of a systematic review.

AIM: To investigate adherence rates in tumor necrosis factor-α (TNF-α)-inhibitors in Crohn's disease (CD) and rheumatoid arthritis (RA) by systematic review of medical literature. METHODS: A structured search of PubMed between 2001 and 2011 was conducted to identify publications that assessed treatment with TNF-α inhibitors providing data about adherence in CD and RA. Therapeutic agents of interest where adalimumab, infliximab and etanercept, since these are most commonly used for both diseases. Studies assessing only drug survival or continuation rates were excluded. Data describing adherence with TNF-α inhibitors were extracted for each selected study. Given the large variation between definitions of measurement of adherence, the definitions as used by the authors where used in our calculations. Data were tabulated and also presented descriptively. Sample size-weighted pooled proportions of patients adherent to therapy and their 95%CI were calculated. To compare adherence between infliximab, adalimumab and etanercept, the adherence rates where graphed alongside two axes. Possible determinants of adherence were extracted from the selected studies and tabulated using the presented OR. RESULTS: Three studies on CD and three on RA were identified, involving a total of 8147 patients (953 CD and 7194 RA). We identified considerable variation in the definitions and methodologies of measuring adherence between studies. The calculated overall sample size-weighted pooled proportion for adherence to TNF-α inhibitors in CD was 70% (95%CI: 67%-73%) and 59% in RA (95%CI: 58%-60%). In CD the adherence rate for infliximab (72%) was highercompared to adalimumab (55%), with a relative risk of 1.61 (95%CI: 1.27-2.03), whereas in RA adherence for adalimumab (67%) was higher compared to both infliximab (48%) and etanercept (59%), with a relative risk of 1.41 (95%CI: 1.3-1.52) and 1.13 (95%CI: 1.10-1.18) respectively. In comparative studies in RA adherence to infliximab was better than etanercept and etanercept did better than adalimumab. In three studies, the most consistent factor associated with lower adherence was female gender. Results for age, immunomodulator use and prior TNF-α inhibitors use were conflicting. CONCLUSION: One-third of both CD and RA patients treated with TNF-α inhibitors are non-adherent. Female gender was consistently identified as a negative determinant of adherence.

Adenomas in patients with inflammatory bowel disease are associated with an increased risk of advanced neoplasia.

BACKGROUND: It is still unclear whether inflammatory bowel disease (IBD) patients with adenomas have a higher risk of developing high-grade dysplasia (HGD) or colorectal cancer (CRC) than non-IBD patients with sporadic adenomas. We compared the risk of advanced neoplasia (AN, defined as HGD or CRC) in IBD patients with adenomas to IBD patients without adenomas and patients without IBD with adenomas. METHODS: IBD patients with a histological adenoma diagnosis (IBD + adenoma), age-matched IBD patients without adenoma (IBD-nonadenoma), and adenoma patients without IBD (nonIBD + adenoma) were enrolled in this study. Medical charts were reviewed for adenoma characteristics and development of AN. The endoscopic appearance of the adenomas was characterized as typical (solitary sessile or pedunculated) or atypical (all other descriptions). RESULTS: A total of 110 IBD + adenoma patients, 123 IBD-nonadenoma patients, and 179 nonIBD + adenoma patients were included. Mean duration of follow-up was 88 months (SD ±41). The 5-year cumulative risks of AN were 11%, 3%, and 5% in IBD + adenoma, IBD-nonadenoma, and nonIBD + adenoma patients, respectively (P < 0.01). In IBD patients atypical adenomas were associated with a higher 5-year cumulative risk of AN compared to IBD patients with typical adenomas (18% vs. 7%, P = 0.03). CONCLUSIONS: IBD patients with a histological diagnosis of adenoma have a higher risk of developing AN than adenoma patients without IBD and IBD patients without adenomas. The presence of atypical adenomas in particular was associated with this increased risk, although patients with typical adenomas were found to carry an additional risk as well.

Substantial impact of illness perceptions on quality of life in patients with Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) negatively impact patients' health-related quality of life (HRQOL). We used the common sense model to examine the contribution of illness perceptions and coping to HRQOL, in addition to clinical and socio-demographic characteristics. This provides insight into potential targets for psychological interventions aimed at improving HRQOL. METHODS: Consecutive CD patients undergoing colonoscopy were included. Disease activity was assessed by a clinical and an endoscopic index. Patients completed questionnaires assessing illness perceptions (IPQ-R), coping (Utrecht Coping List), self-perceived health, neuroticism, and HRQOL. Hierarchical multiple regression analyses were performed to assess the contribution of illness perceptions and coping to HRQOL. Illness perceptions were compared to patients with rheumatoid arthritis, myocardial infarction (MI), and head and neck cancer (HNC). RESULTS: Of 82 CD patients, mean age was 42±14years. Clinical and endoscopic active disease was present in 42 (52%) and 49 (60%) patients, respectively. HRQOL was strongly impaired by clinical active disease (r=-0.79), self-perceived health (r=-0.60), and perceived consequences of CD (r=-0.54), but correlated poorly with endoscopic disease activity (r=-0.29). Illness perceptions significantly contributed 3-27% to HRQOL. Coping had no contributory role. CD patients perceived similarly strong consequences of their illness as patients with MI and HNC and had the strongest thoughts about the chronic nature of their illness. CONCLUSIONS: CD has a similar impact on patients' daily lives as was observed in patients with MI and HNC. Illness perceptions contribute to HRQOL and should therefore be incorporated in clinical practice, thereby improving HRQOL.