Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

Early-onset versus late-onset Crohn's disease: An Italian cohort study.

BACKGROUND: Disease heterogeneity, according to the age at onset, has been reported in Crohn's disease (CD). OBJECTIVE: This study aimed to compare natural history in CD patients diagnosed ≤17 (early onset (EO)) versus ≥60 (late onset (LO)) years old. METHODS: EO CD and LO CD patients referred to two Italian inflammatory bowel disease (IBD) centres were included. Relevant data comprised sex, current smoking, disease location and behaviour, IBD family history, extra-intestinal manifestations and use of medical/surgical therapy during the follow-up period. RESULTS: Among 2321 CD patients, 160 met the inclusion criteria: 92 in the EO and 68 in the LO group (mean follow-up 11.7 ± 7.7 years). Family history of IBD was more frequent in EO compared to LO CD (26% vs. 4%; p < 0.0001). Ileocolonic, upper gastrointestinal and perianal involvement occurred more frequently in EO compared to LO CD (56% vs. 21%, p < 0.0001; 17% vs. 3%, p < 0.01; and 38% vs. 19%, p < 0.01, respectively). Progression to complicated disease occurred more frequently in EO CD (40% vs. 10% p < 0.005), with an increased use of corticosteroids and anti-tumour necrosis factor alpha agents within 10 years since diagnosis (81% vs. 58%, p = 0.004, and 36% vs. 16%, p = 0.01, respectively), while the cumulative probability of surgery did not differ between the two groups. CONCLUSIONS: Patients with EO CD are more likely to develop a more aggressive disease with perianal involvement and a greater use of drug treatment compared to those with LO CD, without carrying an increased need for surgery.

Late-onset Crohn's disease: a comparison of disease behaviour and therapy with younger adult patients: the Italian Group for the Study of Inflammatory Bowel Disease 'AGED' study.

BACKGROUND: Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS: In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS: A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF's even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn's disease patients. CONCLUSION: Thirty-two percent of late-onset Crohn's disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.

Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II).

OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported. DESIGN: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up. RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis. CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development. TRIAL REGISTRATION NUMBER: NCT01287897 and NCT01345318.

Management of ulcerative colitis in a real-life setting: An Italian multicenter, prospective, observational AIGO study.

BACKGROUND: No data are available on the variability in the clinical management of ulcerative colitis (UC) patients by Italian gastroenterologists. Therefore, improving the standards of UC care as provided by the National Welfare Clinical Path (PDTA), in accordance with the European Crohn's and Colitis Organization (ECCO) guidelines for UC, is not easy. AIMS: To assess the management of UC by Italian gastroenterologists in a real-life setting taking into account its variability. METHODS: This prospective, cross-sectional, observational study included IBD-specialized gastroenterologists (GSIBDs) and general gastroenterologists (GGs) working in Italian public hospital units. Consecutive patients with an UC flare were enrolled and the medical treatment evaluated. For each center, the physician in charge of the study (16 GSIBDs and 10 GGs) was administered two electronic questionnaires. RESULTS: Among 26 units, 573 UC patients were enrolled. Good adherence to the European guidelines was reported; GSIBDs reported greater adherence than GGs with a higher prescription of rectal and combination therapy in mild to moderate distal disease and a higher rate of hospitalization in severe UC. CONCLUSION: The management of UC by Italian gastroenterologists in clinical practice is good according to the ECCO consensus recommendations, though some discrepancies are present between GSIBDs and GGs.

Therapeutic Drug Monitoring is More Cost-Effective than a Clinically Based Approach in the Management of Loss of Response to Infliximab in Inflammatory Bowel Disease: An Observational Multicentre Study.

BACKGROUND AND AIMS: Empirical dose intensification and therapeutic drug monitoring [TDM] of infliximab [IFX] trough levels [ITLs] and antibody to infliximab [ATI] assays are recognized approaches for managing loss of response [LoR] in patients with inflammatory bowel disease [IBD]. The aim of the study was to compare these two interventions in a clinical setting, in terms of effectiveness and cost savings. METHODS: Consecutive IBD patients experiencing LoR were clinically managed according to a TDM algorithm. A historical group of empirically treated patients, for whom sera for ITLs and ATI assays had been collected, served as the control group. Clinical outcomes 12 weeks after the therapeutic interventions were compared between the two groups. A cost-minimization analysis was performed to compare the economic impact of these two approaches. RESULTS: Ninety-six patients were enrolled prospectively and compared with 52 controls. The two cohorts were similar in characteristics and in the distribution of TDM results. In the prospective cohort, however, we observed less IFX dose escalations compared with in the controls [45% versus 71%, p = 0.003]. Also, more patients were switched to a different anti-TNFα in the prospective cohort than in the control cohort [25% versus 4%, p = 0.001]. The percentages of patients achieving a clinical response at 12 weeks were 52% and 54% for the prospective and control groups, respectively. By cost analysis, we estimated a savings of 15% if the TDM algorithm was applied. CONCLUSIONS: In our population, applying a TDM algorithm for LoR to IFX resulted in less dose escalations, without loss of efficacy, compared with empirical adjustment. In addition, the TDM approach was cost-effective.

Population-based cohort study on comparative effectiveness and safety of biologics in inflammatory bowel disease.

BACKGROUND: The comparison of effectiveness and safety of anti-tumor necrosis factor-alpha agents for the treatment of inflammatory bowel disease (IBD) is relevant for clinical practice and stakeholders. OBJECTIVE: The objective of this study was to compare the risk of abdominal surgery, steroid utilization, and hospitalization for infection in Crohn's disease (CD) or ulcerative colitis (UC) patients newly treated with infliximab (IFX) or adalimumab (ADA). METHODS: A retrospective population-based cohort study was performed using health information systems data from Lazio region, Italy. Patients with CD or UC diagnosis were enrolled at first prescription of IFX or ADA during 2008-2014 (index date). Only new drug users were followed for 2 years from the index date. IFX versus ADA adjusted hazard ratios were calculated applying "intention-to-treat" approach, controlling for several characteristics and stratifying the analysis on steroid use according to previous drug utilization. Sensitivity analyses were performed according to "as-treated" approach, adjusting for propensity score, censoring at switching or discontinuation, and evaluating different lengths of follow-up periods. RESULTS: We enrolled 1,432 IBD patients (42% and 83% exposed to IFX for CD and UC, respectively). In both diseases, treatment effects did not differ in any outcome considered, and sensitivity analyses confirmed the results from the main analysis. CONCLUSION: In our population-based cohort study, effectiveness and safety data in new users of ADA or IFX with CD or UC were comparable for the outcomes we tested.

Patient and physician views on the quality of care for inflammatory bowel disease after one-year follow-up: Results from SOLUTION-2, a prospective IG-IBD study.

BACKGROUND AND AIMS: Perception of quality of care is important in the management of patients with chronic diseases, particularly inflammatory bowel disease. AIMS AND METHODS: This longitudinal study aimed to investigate variations of the Quality of Care through the Patients' Eyes (QUOTE-IBD) questionnaire scores one year after the basal evaluation in the Studio Osservazionale quaLità cUre malatTIe crOniche intestiNali (SOLUTION-1) study. RESULTS: Of the cohort of 992 patients, 936 were evaluable. The QUOTE-IBD score overcame satisfactory levels of more than the 80%, overall and in all subdomains except for the "Continuity of Care" sub-dimension (mean, 8.3; standard deviation, 1.49), scored satisfactory only by 34% of the patients. No significant changes in satisfaction were recorded overall, or considering patients subgroups. Significant differences were found at the end of the follow-up between physicians' and patients' perceptions of quality of care, with the former over-rating their performance in "Continuity of Cares" and under-rating "Costs", "Competence", and "Accessibility" sub-domains of the score (p<0.05 for all). CONCLUSION: Perceived quality of care in a large cohort of Italian patients with inflammatory bowel disease remains unchanged after one-year follow-up and was not significantly affected by disease activity or therapeutic interventions. Differences between physicians' and patients' perceptions of quality of care should be taken into account.

Use of corticosteroids and immunosuppressive drugs in inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease.

The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn's disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.

The Time Course of Diagnostic Delay in Inflammatory Bowel Disease Over the Last Sixty Years: An Italian Multicentre Study.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] patients are still under-diagnosed or diagnosed with serious delay. We examined whether diagnostic delay [DD] in IBD has changed over the last 60 years, and explored the risk factors of longer DD. METHODS: In total, 3392 IBD patients recorded in the registry of four IBD Italian centres were divided according to the year of diagnosis into a historical cohort [HC: 1955-84] and modern cohort [MC: 1985-2014]. DD, i.e. time lapse between onset of symptoms indicative of IBD and definitive diagnosis, was divided into four sub-periods [0-6, 7-12, 13-24, >24 months], which were correlated with age and disease location/behaviour at diagnosis. RESULTS: Median DD in IBD was 3.0 months, it was significantly [P < 0.0001] higher in Crohn's disease [CD] [7.1 months] than in ulcerative colitis [UC] [2.0 months], and did not differ either between the HC and the MC or over the last three decades. However, the proportion of patients with a DD>24 months was significantly [P < 0.0001] higher in the HC [26.0%] than in the MC [18.2%], and the same trend was evident over the last three decades [1985-94: 19.9%; 1995-2004: 16.4%; 2005-14: 13.9%; P = 0.04]. At logistic regression analysis, age at diagnosis >40 years (CD: odds ratio 1.73, 95% confidence interval [CI] 1.31-2.28, P < 0.0001; UC: 1.41, 95% CI 1.02-1.96, P = 0.04) and complicated disease at CD diagnosis [1.39, 95% CI 1.06-1.82, P = 0.02] were independently associated with a DD>24 months. CONCLUSIONS: DD duration has not changed over the last 60 years in Italy, but the number of IBD patients with a longer DD significantly decreased. Older age at diagnosis and a complicated disease at CD diagnosis are risk factors for longer DD.

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

The PROSIT-BIO Cohort: A Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Infliximab Biosimilar.

BACKGROUND: Few data are available on the safety and efficacy of infliximab biosimilar CT-P13 in patients with ulcerative colitis and Crohn's disease. METHODS: A prospective, multicenter, cohort study using a structured database. RESULTS: Consecutive patients (313 Crohn's disease and 234 ulcerative colitis) were enrolled from 31 referral centers; 311 patients were naive to anti-tumor necrosis factor alpha, 139 had a previous exposure to biologics, and the remaining 97 were switched to CT-P13 after a mean of 18 ± 14 infusions of infliximab. The mean follow-up was 4.3 ± 2.8 months, and the total follow-up time was 195 patient-years. After 2061 infusions, 66 serious adverse events were reported (12.1%), 38 (6.9%) of them were infusion-related reactions. The biosimilar had to be stopped in 29 (5.3%) cases for severe infusion reactions (8 naive, 19 previous exposed, and 2 switch), and in further 16 patients (2.9%) for other serious adverse events. Infusion reactions were significantly more frequent in patients pre-exposed to infliximab than to other anti-tumor necrosis factor alpha (incidence rate ratio = 2.82, 95% CI: 1.05-7.9). The efficacy of the biosimilar was evaluated in 434 patients who received treatment for at least 8 weeks, using time-to-event methods for censored observations: 35 patients were primary failures (8.1%). After further 8, 16, and 24 weeks, the efficacy estimations were 95.7%, 86.4%, and 73.7% for naive, 97.2%, 85.2%, and 62.2% for pre-exposed, and 94.5%, 90.8%, and 78.9% for switch, respectively (log-rank P = 0.64). CONCLUSIONS: Although no direct comparison was performed, preliminary data on efficacy and safety of CT-P13 were in line with those of infliximab.

Disease patterns in late-onset ulcerative colitis: Results from the IG-IBD "AGED study".

BACKGROUND: Late-onset UC represents an important issue for the near future, but its outcomes and relative therapeutic strategies are yet poorly studied. AIM: To better define the natural history of late-onset ulcerative colitis. METHODS: In a multicenter retrospective study, we investigated the disease presentation and course in the first 3 years in 1091 UC patients divided into 3 age-groups: diagnosis ≥65years, 40-64 years, and <40years. Disease patterns, medical and surgical therapies, and risk factors for disease outcomes were analyzed. RESULTS: Chronic active or relapsing disease accounts for 44% of patients with late-onset UC. Across all age-groups, these disease patterns require 3-6 times more steroids than remitting disease, but immunomodulators and, to a lesser extent, biologics are less frequently prescribed in the elderly. Advanced age, concomitant diseases and related therapies were found to be inversely associated with the use of immunomodulators or biologics, but not with surgery. CONCLUSIONS: The conclusion that late-onset UC follows a mild course may apply only to a subset of patients. an important percentage of elderly patients present with more aggressive disease. Since steroid use and surgery rates did not differ in this subgroup, lower use of immunosuppressive therapy and biologics may reflect concerns in prescribing these therapies in the elderly.

Inflammatory bowel disease nurse specialists for patients on biological therapies: a nationwide Italian survey.

BACKGROUND: Management of inflammatory bowel disease (IBD) patients requires a multidisciplinary approach. Among the working team, the role of IBD nurse is expected to be particularly relevant when managing patients receiving biological therapies. We performed a survey to assess the presence of IBD nurse in centers where patients were receiving biologics. METHODS: For this Italian nationwide survey a specific questionnaire was prepared. IBD nurse was defined as a nurse directly involved in all phases of biological therapy, from pre-therapy screening, administration and monitoring during therapy, to follow up performed by a dedicated helpline, completed a specific training on biological therapy therapy, and observed international guidelines. RESULTS: A total of 53 Italian IBD centers participated in the survey, and 91 valid questionnaires were collected. Overall, 34 (37.4%) nurses could be classified as IBD specialists. IBD nurses had a significantly higher educational level than other nurses, they were more frequently operating in Central or Southern than in Northern Italy, they were working in an Academic center rather than in a General hospital, and in IBD centers with >25 patients on biological therapy. On the contrary, mean age, gender distribution, years of nursing, and years working in the IBD unit did not significantly differ between IBD and other nurses. CONCLUSIONS: Our nationwide survey showed that the presence of an IBD nurse is still lacking in the majority of Italian IBD centers where patients receive biological therapies, suggesting a prompt implementation.

Curcumin and Fennel Essential Oil Improve Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Irritable Bowel Syndrome (IBS) patients still require effective treatment. The anti-inflammatory property of curcumin and the antispasmodic and carminative effect of fennel suggests that combination of these nutraceutical compounds would be useful in functional bowel disorders including IBS. We assessed the efficacy and tolerability of a combination of curcumin and fennel essential oil (CU-FEO) in IBS symptoms relief. METHODS: 121 patients with mild-to-moderate symptoms of IBS defined by an Irritable Bowel Syndrome- symptom severity score (IBS-SSS) 100-300 and abdominal pain score 30-70 on a 100 mm Visual Analogue Scale (VAS), were randomly assigned to CU-FEO or placebo (2 capsules b.d. for 30 days). Primary endpoint was the mean decrease of IBS-SSS at the end of the treatment corrected for the mean baseline score (relative decrease). The impact of the treatment on quality of life was assessed through IBS-QoL questionnaire. RESULTS: CU-FEO was safe, well-tolerated and induced symptom relief in patients with IBS; a significant decrease in the mean relative IBS-SSS was observed after 30 days of treatment (50.05 +/- 28.85% vs 26.12 +/- 30.62%, P<0.001). This result matched the reduction of abdominal pain and all the other symptoms of IBS-SSS. The percentage of symptom-free patients was significantly higher in the CU-FEO than in the placebo group (25.9% vs. 6.8%, P = 0.005). All domains of IBS-QoL improved consistently. CONCLUSION: CU-FEO significantly improved symptoms and quality of life in IBS patients over 30 days.

Inflammatory Bowel Disease Phenotype as Risk Factor for Cancer in a Prospective Multicentre Nested Case-Control IG-IBD Study.

BACKGROUND AND AIMS: Cancer risk in inflammatory bowel disease [IBD] is still debated. In a prospective, multicentre, nested case-control study, we aimed to characterise incident cases of cancer in IBD. The role of immunomodulators vs clinical characteristics of IBD as risk factors for cancer was also investigated. MATERIALS AND METHODS: From January 2012 to December 2014, each IBD patient with incident cancer was matched with two IBD patients without cancer for: IBD type, gender, and age. Risk factors were assessed by multivariate regression analysis. RESULTS: IBD patients considered numbered 44619: 21953 Crohn's disease [CD], 22666 ulcerative colitis [UC]. Cancer occurred in 174 patients: 99 CD [CD-K], 75 UC [UC-K]. Controls included 198 CD [CD-C], 150 UC [UC-C]. Cancer incidence in IBD was 3.9/1000, higher in CD (4.5/1000 [99/21,953]) than in UC (3.3/1000 [75/22,666]; p = 0.042). Cancers involved: digestive system [36.8%], skin [13.2%], urinary tract [12.1%], lung [8.6%], breast [8%], genital tract [6.9%], thyroid [4.6%], lymphoma [3.5%], others [6.3%]. In CD, penetrating behaviour and combined thiopurines and tumour necrosis factor alpha [TNFα] antagonists were risk factors for cancer overall: odds ratio [OR] (95% confidence interval [CI] 2.33 [1.01-5.47]); 1.97 [1.1-3.5]; and for extracolonic cancers 3.9 [1.56-10.1]; 2.15 [1.17-4.1], respectively. In UC, risk factors were pancolitis and disease-related surgery for cancer overall (OR: 2.52 [1.26-5.1]; 5.09 [1.73-17.1]); disease-related surgery for colorectal cancer [CRC] (OR 3.6 [1.0-12]); and extensive and left-sided vs distal UC for extracolonic cancers (OR: 2.55 [1.15-5.9]; 2.6 [1.04-6.6]), respectively. CONCLUSIONS: In a multicentre study, penetrating CD and extensive UC were risk factors for cancer overall. Cancer incidence was higher in CD than in UC.

Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity.

BACKGROUND: A CD4+CD25- regulatory T cell population expressing the surface TGF-ß in its latent form LAP+ [latency associated peptide] cells was proved to be protective in experimental colitis and to be suppressive of human peripheral blood [PB] T proliferation. We investigated the frequency and function of lamina propria [LP] CD4+LAP+ T cells in inflammatory bowel disease [IBD] patients. METHODS: Specimens from patients undergoing colonoscopy or bowel resection for IBD and colonic cancer were used as source of lamina propria mononuclear cells [LPMC]. The ulcerative colitis [UC] group was divided according to endoscopic activity evaluated with modified Baron Score. IL-17, IFN-γ, IL-10, LAP, and Foxp3 expression in CD3+CD8- [CD4] or CD3+/CD4+ gated cell population was assessed by immunofluorescence. The ability of FACS-sorted LP CD3+CD8-[CD4] LAP+CD25- to inhibit stimulated autologous PB CD3+CD8-[CD4] LAP- CD25- cells proliferation was assessed. RESULTS: LP CD4LAP+ cells were significantly increased, when compared with controls, in active UC patients and not in Crohn's disease patients. The majority of LP CD4+LAP+ cells were Foxp3-. The percentage of IL-17+ cells in LP CD3+CD8-[CD4] LAP+ cells was significantly higher in active UC patients when compared with controls. LP CD3+CD8-[CD4]LAP+CD25- isolated from UC patients showed reduced or no ability to inhibit autologous PB CD3+CD8-[CD4]LAP-CD25- cell proliferation when compared with controls. Removal of IL-17+ cells from LP CD3+CD8-[CD4] LAP+ cells increases their suppressive ability. CONCLUSIONS: The percentage of LP CD4LAP+ cells is increased in active UC, showing reduced suppressor activity due to their increased proportion of intracellular IL-17 expression.

How thiopurines are used for the treatment of inflammatory bowel diseases: an Italian survey.

BACKGROUND: The ideal manner of thiopurine use in inflammatory bowel disease has not been defined. We aimed at investigating the attitudes of Italian gastroenterologists on thiopurine use. METHODS: A web-based survey was performed among 295 gastroenterologists. RESULTS: Overall, 70 surveys were completed. At baseline, thiopurine methyltransferase genotype and phenotype were not assessed by 87.1% and 97.1% of respondents, respectively. At treatment onset, 17.1% adopted full weight-calculated dose while 80.0% preferred escalating the dose. During treatment, 87.1% and 64.3% reduced the dose for myelo- and liver toxicity, respectively; 48.6% for increased pancreatic enzymes, 17.1% for fever, and 5.7% for arthralgia. A systematic shift from one thiopurine to the other was reported by 4.3% of respondents in case of failure, and by 5.7% for adverse effects. Forty-four gastroenterologists (62.9%) stopped thiopurine treatment after 5-7 years. CONCLUSIONS: Several discrepancies regarding the use of thiopurines in clinical practice were found, deviating from available guidelines. A more standardised attitude is needed in clinical practice.

Patient and physician views on the quality of care in inflammatory bowel disease: results from SOLUTION-1, a prospective IG-IBD study.

INTRODUCTION: Remarkable differences in quality of care (QoC) might be observed in different countries, affecting quality of life of inflammatory bowel disease (IBD) patients. The aim of this study was to assess patient and physician perceptions of the QoC in Italy. METHODS: A multicentre observational study on the quality of care in IBD (SOLUTION-1) was conducted in 36 IG-IBD (Italian Group for Inflammatory Bowel Disease) centres in Italy. The QUOTE-IBD (Quality of Care Through the Patient's Eyes) questionnaire was administered to IBD patients and to the attending physicians. The Quality Impact (QI) score summarises the QUOTE-IBD questionnaire, and a QI >9 is considered satisfactory. RESULTS: Nine-hundred-ninety-two patients and 75 physicians completed the QUOTE-IBD questionnaire. The patients scored the domains of competence (9.47 vs. 8.55) and costs (9.54 vs. 8.26) higher that the physicians, while information (9.31 vs. 9.43) and continuity of care (8.40 vs. 9.01) were scored lower. The QI score was rated worse by physicians with less experience (<12 years) with regard to competence (8.0 vs. 9.01), courtesy (8.12 vs. 10.0) and autonomy (8.97 vs. 10.0). Physicians considered the cost domain unsatisfactory. CONCLUSIONS: Healthcare was rated as satisfactory overall for Italian patients and physicians. The physicians underestimate their competence and consider the cost of medical management unsatisfactory. The patients are more critical regarding the continuity of care and information. Country-specific data on QoC allow local governments to allocate resources more effectively.