Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn's disease--modelling outcomes in active luminal and fistulizing disease in adults

Background  Infliximab has been shown to be efficacious in moderate-to-severe Crohn's disease (CD).
Aim  To evaluate the cost-effectiveness of scheduled maintenance treatment with infliximab in luminal and fistulizing CD patients.
Methods  Markov models were constructed to simulate the progression of adult CD patients with and without fistulae during treatment with infliximab (5 mg/kg). Transitions were estimated from published clinical trials of infliximab. Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. An average weight of 60 kg was used to estimate the dose of infliximab. The costs and outcomes were discounted at 3.5% over 5 years. The primary effectiveness measurement was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs and utilities.
Results  The incremental cost per QALY gained was £26 128 in luminal CD and £29 752 in fistulizing CD at 5 years. Results were robust and remained in the range of £23 752–£38 848 for luminal CD and £27 047–£44 206 for fistulizing CD. Patient body weight was the most important factor affecting cost-effectiveness.
Conclusion  Eight-week scheduled maintenance treatment with infliximab is a cost-effective treatment for adult patients suffering from active luminal or fistulizing CD.     

Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections

Background There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD). Aim To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD. Methods We assembled a cohort study of patients with IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile. Results Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person‐years (95% confidence interval 2.1–6.2) for other immunosuppressive agents to 7.4 (3.3–19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47–4.24). Clostridium difficile infections occurred in 0/1000 (0–5.4) among 521 infliximab initiations and 14/1000 (10.6–18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9–6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose‐dependent nor duration‐dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events). Conclusions In a population‐based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients.     

Infliximab dependency in children with Crohn's disease

Background  Recently, infliximab dependency has been described.
Aim  To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000–2006 and to describe clinical and genetic predictors of long-term infliximab response.
Methods  A phenotype model of infliximab dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start) – complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse ≤90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF -308 A>G, TNF -857 C>T, Casp9 93 C>T, FasL -844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed.
Results  Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24–22.55; OR 6.7, 95% CI: 1.67–26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders ( P  = 0.0002).
Conclusions  Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype.     

Systematic review: the short-term and long-term efficacy of adalimumab following discontinuation of infliximab

Background  Therapy with adalimumab has been shown to be effective in Crohn's disease (CD) patients who have lost response or are intolerant to infliximab.
Aim  To determine the efficacy of adalimumab in CD patients who discontinued infliximab through a systematic review.
Methods  Electronic searches of EMBASE and MEDLINE databases up to May 1, 2009, as well as abstracts from the AGA (2006–2008), ACG (2006–2007), UEGW (2006–2008) and CDDW (2006–2009) identified randomized-controlled trials (RCT) or open-labelled cohorts (OLC) evaluating the short-term and/or long-term efficacy of adalimumab in infliximab failures. The response rates for short-term (clinical response and remission at 4 weeks) and long-term (remission at 6 and 12 months) efficacy were considered.
Results  A total of 1810 CD patients were identified among the 15 studies (2 RCT and 13 OLC). The majority of studies evaluated CD patients who either lost response or were intolerable to infliximab, although five OLCs permitted patients refractory to infliximab. Short-term clinical response ( n  = 9 articles) ranged from 41% to 83%. Long-term clinical remission at 12 months ( n  = 8 articles) ranged from 19% to 68%. The occurrence of severe adverse events ranged from 0% to 19% and four patients died.
Conclusions  Current RCT and OLC evidence suggest that adalimumab is an efficacious therapy for CD patients who discontinue infliximab.     

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey

Background  Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain.
Aim  To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD).
Methods  A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond.
Results  A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity ( P  = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy.
Conclusions  The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD.     

Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease

Background  Osteoporosis is a recognized complication of inflammatory bowel disease (IBD).
Aim  To investigate the role of environmental factors and vitamin D receptor (VDR) variants on the prevalence of osteoporosis.
Methods  DEXA scans and case note review were performed on 440 IBD patients from 1997 to 2006. All the IBD patients and 240 healthy controls were genotyped for VDR variants Taq -1 and Apa -1 using PCR-RFLP.
Results  Osteoporosis and osteopenia rates were 15% and 18% for IBD, 16% and 18% for Crohn's disease (CD) and 13% and 19% for ulcerative colitis, respectively. On univariate analysis of the CD patients, low body mass index (BMI, <18.5) and smoking status ( P  = 0.008 and 0.005 respectively) were associated with osteoporosis and osteopenia. Low BMI was also associated with osteoporosis on multivariate analysis in CD ( P  = 0.021, OR 5.83, CI 1.31–25.94). No difference was observed between Taq -1 and Apa -1 VDR polymorphisms in IBD, CD, ulcerative colitis and healthy controls. However, CD males were more likely to carry the variant Taq -1 polymorphism than healthy controls males ( P  = 0.0018, OR 1.94, CI 1.28–2.92) and female CD patients ( P  = 0.0061, OR 1.60, CI 1.17–2.44).
Conclusions  In this well-phenotyped cohort of IBD patients, a relatively low prevalence of osteoporosis was observed. Low BMI was the only independent risk factor identified to be associated with osteoporosis.     

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis

Background  Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis.
Aim  To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease.
Methods  Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n  = 5073).
Results  A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n  = 46, mesalazine (mesalamine) n  = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P  = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6–20.6; P  = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n  = 1477) (OR 5.2 95% CI: 1.8–14; P  = 0.002).
Conclusions  The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.     

Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method

Background  Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described.
Aim  To assess the effectiveness of a corticosteroid withdrawal method.
Methods  Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29–75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean.
Results  Median durations for disease and corticosteroid dependency were 21 (range 3–45) and 14 (range 2–45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5–73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean ( P  = 0.056).
Conclusions  Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients.     

Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease

Background  Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described.
Aim  To explore potential interactions between thiopurines and concomitant medications.
Methods  A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments.
Results  Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7–29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose ( P  =   0.016).
Conclusions  Our data suggest the absence of significant interactions between thiopurines and 5-ASA.     

Increased plasma ghrelin following infliximab in Crohn's disease

Background  Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators.
Aim  To assess the effect of an anti-TNFα antibody on ghrelin in patients with Crohn's disease (CD).
Methods  Fifteen patients with Crohn's receiving infliximab were studied before and 1 week after infusion. Following an overnight fast, blood was sampled before a meal and then every 20 min for 2 h. Total ghrelin and CRP were measured using ELISA. Acylated ghrelin and TNFα, IFNγ, IL-1β and IL-6 were measured with bioplex. Harvey Bradshaw Activity Index was assessed.
Results  Median (95% CI) 2-h integrated plasma total ghrelin increased from 162 (99–311) before infliximab to 200 (128–387) pg/mL h, ( P  = 0.02) after. Following infliximab, 20 min postmeal, median acylated ghrelin decreased from 50.3 (24–64) to 38.6 (26–82) pg/mL, ( P  = 0.04) thus reverting to a traditional meal related ghrelin curve. Median (range) disease activity decreased from 5 (2–28) before to 3 (0–22), ( P  = 0.0001) and Median (95% CI) TNFα decreased from 2.8 (1.89–4.48) to 1.31 (0.73–2.06) pg/mL ( P  = 0.002).
Conclusions  Infliximab increases circulating total ghrelin by 25% in CD and restores the postprandial response of acylated ghrelin to food intake. Acylated and de-sacyl ghrelin remain unchanged, suggesting that an alternate isoform could be affected by infliximab.     

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England

Background  Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC).
Aim  To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC.
Methods  A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres.
Results  Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4–59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8–13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media.
Conclusion  Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.     

Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials

Background  Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated.
Aim  To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients.
Methods  Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non-use).
Results  Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity.
Conclusion  Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab.     

Tamoxifen and risk of idiopathic venous thromboembolism

Aims To evaluate a possible positive association between tamoxifen treatment and the risk of developing idiopathic venous thromboembolism (VTE) in women with breast cancer in the absence of clinical risk factors for venous thromboembolism other than breast cancer itself.
Methods Using information from the large UK-based General Practice Research Database, we identified, within a cohort of more than 10 000 women with breast cancer, all women who developed a first-time diagnosis of deep vein thrombosis or pulmonary embolism of uncertain cause between January 1, 1991 and December 31, 1996. In a case-control analysis, we compared their tamoxifen exposure experience prior to the thromboembolic event with that of a randomly selected group of control women with breast cancer who were matched to cases on age, year of the breast cancer diagnosis and calendar time.
Results We identified 25 cases of idiopathic VTE and 172 controls, all of whom had breast cancer, but were otherwise free from other risk factors for VTE. Past tamoxifen exposure was not materially associated with an elevated risk of developing VTE, and we therefore combined never and past users as reference group. The relative risk estimate of VTE for current tamoxifen exposure, as compared with never and past use combined, was 7.1 (95% CI 1.5–33), adjusted for body mass index, smoking status and hysterectomy status. High body mass index was an independent predictor of VTE itself.
Conclusions Our study provides evidence that current use of tamoxifen increases the risk of idiopathic venous thromboembolism.     

The association between coeliac disease and cardiovascular disease

Background  Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear.
Aim  To investigate whether coeliac disease patients have an increased risk of cardiovascular events.
Methods  A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study.
Results  The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4–14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6–10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00–3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22–5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort ( P  = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort ( P  < 0.01).
Conclusion  Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.     

Drugs to Treat Systemic Lupus Erythematosus: Relationship between Current Use and Cardiovascular Risk Factors

Objectives.  Cardiovascular risk is increased in patients with systemic lupus erythematosus (SLE). Drugs used to treat SLE can modify traditional cardiovascular risk factors. We examined the effect of selected drugs used in the treatment of SLE on cardiovascular risk factors.
Methods.  We compared systolic and diastolic blood pressure, serum lipid concentrations, glucose, homocysteine, and urinary F₂-isoprostane concentrations in 99 patients with lupus who were either current users or non-users of systemic corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 selective NSAIDs, azathioprine, and methotrexate. Multivariable adjustment was done with linear regression modeling using sex, age and disease activity (SLEDAI) as controlling variables.
Results.  Serum triglyceride concentrations were higher (135.1 ± 61.4 vs. 95.3 ± 47.5 mg/dL, adjusted P  = 0.003) in patients receiving corticosteroids. Homocysteine concentrations were marginally higher in patients receiving methotrexate (adjusted P  = 0.08). Current use of either NSAIDs or COX-2 inhibitors was not associated with increased cardiovascular risk factors. Current hydroxychloroquine use was not associated with significant alterations in lipid profiles.
Conclusions.  In a non-random sample of patients with SLE, current corticosteroid use was associated with increased triglyceride concentrations, but other drugs had little effect on traditional cardiovascular risk factors.     

The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up

Background  Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC).
Aim  To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007.
Methods  Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0–4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab.
Results  Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious).
Conclusions  Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy.     

Meta-analysis: incidence of endoscopic gastric and duodenal ulcers in placebo arms of randomized placebo-controlled NSAID trials

Background  The safety of NSAIDs is often evaluated by comparison with placebo in clinical trials.
Aim  To investigate the incidence of gastric and duodenal ulcers (GDU) in placebo arms in NSAID trials over the last three decades.
Methods  Randomized placebo-controlled trials of oral NSAIDs from 1975 to 2006 were systematically reviewed. The pooled incidence of GDU in placebo arms was calculated and compared. Meta-regression was used to identify risk factors related to the incidence of the placebo ulcer at the study level.
Results  Thirty-six studies met inclusion criteria (duration of 6.5 days to 24 weeks). In total, 3.29% GDUs were reported in 36 placebo arms. The incidence of GDU in placebo arms was 0, 4.20% and 3.03% in the studies from 1975–1989, 1990–1999 and 2000–2006 respectively ( P  > 0.05). Eligible subjects with previous GI events and eligible subjects on co-therapy with low-lose aspirin/corticosteroids were associated with the increase in placebo ulcer incidence after adjusting for other factors.
Conclusions  The incidence of GDU in placebo arms has not changed significantly over the last three decades, although has decreased in the past 10 years. Studies show that previous GI events and co-therapy with low-dose aspirin/corticosteroids were associated with increasing GDU in placebo arms.     

High therapy adherence but substantial limitations to daily activities amongst members of the Dutch inflammatory bowel disease patients' organization: a patient empowerment study

Background  Adherence is important for successful treatment in inflammatory bowel disease (IBD) patients. Previous studies demonstrated high prevalence of non-adherence.
Aim  To assess IBD-patients' perceptions of therapy adherence and disease-related functional status in members of the Dutch patients' association of Crohn's disease and ulcerative colitis (CCUVN).
Methods  Inflammatory bowel disease-patients completed anonymously a survey at the website of the CCUVN. Statistical analysis was performed using principal component analysis, univariate and multivariate logistic regression.
Results  The questionnaire was completed by 1067 patients [617 (58%) Crohn's disease (CD) and 450 (42%) ulcerative colitis (UC)]. Mean age was 43 years (s.d. 13.7); women (66%). Of 920 patients currently using medication, 797 (87%) were adherent. Of the patients using 5-ASA, 91% were adherent (527/582), vs. 96% using corticosteroids (316/330) and 97% (414/425) using immunosuppressives. CD patients (OR 1.54; 95% CI 1.05–2.27), patients with duration of disease ≤8 years (OR 2.25; 95% CI 1.49–3.39) were more adherent. Fifty percent of patients reported a low functional status and were limited in daily activities.
Conclusion  This population-based study shows high therapy adherence, but low functional status in Dutch CCUVN-related IBD-patients. The high adherence rate in this present study could be an effect of CCUVN membership.     

Proton pump inhibitors increase significantly the risk of Clostridium difficile infection in a low-endemicity, non-outbreak hospital setting

Background  Proton pump inhibitors (PPI) have been linked to higher risk of Clostridium difficile infection (CDI). The relevance of this association in hospitals with low disease activity, where an outbreak strain is nondominant, has been assessed in relatively few studies.
Aim  To assess the association of PPI and CDI in a setting of low disease activity.
Methods  A retrospective cohort study was conducted at two hospitals. Patients admitted for ≥7 days receiving antibiotics were included. Demographics, exposure to PPI, antibiotics and other drugs in relation to diagnosis of CDI were assessed by univariate and multivariate analyses.
Results  Of 14 719 patients, 149 (1%) first episode CDI were documented; PPI co-exposure increased CDI [1.44 cases/100 patients vs. 0.74 cases/100 non-exposed (OR: 1.96, 95% CI: 1.42–2.72)]. By logistic regression, PPI days (adjusted OR: 1.01 per day, 95% CI: 1.00–1.02), histamine-2 blockers, antidepressants, antibiotic days, exposure to medications, age, admission service and length of admission were significant predictors.
Conclusions  A statistically significant increase in CDI was observed in antibiotic recipients who received PPI, but the absolute risk increase is modest. In settings of with low rates of CDI, the benefit of PPI therapy outweighs the risk of developing CDI. These data support programmes to decrease inappropriate use of PPI in hospitalized patients.