Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. OBJECTIVES: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. METHODS: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. RESULTS: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn's disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn's disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. CONCLUSIONS: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients' protection during follow-up as immunity may wane faster in this population.

TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User's Guide: An Update.

BACKGROUND: Anti-tumour necrosis factor-alpha (anti-TNF) antagonists have been the mainstay in the treatment of inflammatory bowel diseases (IBDs) for over 20 years. SUMMARY: This review article aimed to provide an update on recent advances in TNF antagonist therapy for IBDs. Key Messages: Their position in the treatment algorithm has evolved to "rapid step-up therapy" or "top-down therapy" according to disease severity and patients' characteristics. Limitations of anti-TNF antagonists include loss of response in up to 30-50% of patients with or without the development of antibodies. Therapeutic drug monitoring should provide a tailored, personalized approach to this scenario. Recently, biosimilar agents have been approved for IBDs and are considered equivalent in efficacy to the originator.

Treatment Algorithms for Crohn's Disease.

BACKGROUND: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. SUMMARY: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD - especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus.

BACKGROUND: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. METHODS: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. RESULTS: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn's disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 µg/mL, adalimumab 8 µg/mL, certolizumab pegol 10 µg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. CONCLUSION: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

Differences in Outcomes Reported by Patients With Inflammatory Bowel Diseases vs Their Health Care Professionals.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) scoring systems combine patient-reported data with physicians' observations to determine patient outcomes, but these systems are believed to have limitations. We used real-world data from a large IBD cohort in Switzerland to compare results between patients and healthcare professionals from scoring systems for Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data from the Swiss IBD cohort, beginning in 2006, using 2453 reports for 1385 patients (52% female, 58% with CD). During office visits, physicians asked patients about signs and symptoms and recorded their answers (health care professional-reported outcomes). On a later date, patients received a questionnaire at home (independently of the medical visit), complete it, and sent it back to the data center. Patients also completed the short form 36 and IBD quality of life (QoL) questionnaires. We calculated Cohen's kappa (κ) statistics to assess the level of agreement in scores between patients and health care professionals (Δt between reports collected less than 2 months apart). We used Spearman correlation coefficients (ρ) to compare general well-being (GWB) and QoL scores determined by patients vs health care professionals. Our primary aim was to investigate the overall and individual level of agreement on signs and symptoms reported by health care professionals vs patients. RESULTS: The best level of agreement (although moderate) was observed for number of stools last week in patients with CD (κ = 0.47), and nocturnal diarrhea in patients with UC (κ = 0.52). Agreement was low on level of abdominal pain (κ = 0.31 for patients with CD and κ = 0.37 for patients with UC) and GWB (κ = 0.23 for patients with CD and κ = 0.26 for patients with UC). Patients reported less severe abdominal pain and worse GWB (CD) or better GWB (UC) than that determined by health care professionals. Patient self-rated GWB correlated with IBD quality of life (ρ = 0.68 for patients with CD and ρ = 0.70 for patients with UC) and SF-36 physical scores (ρ = 0.55 for patients with CD and ρ = 0.60 for patients with UC); there was no correlation between health care professional-rated GWB and QoL. CONCLUSIONS: In a comparison of patient vs health care provider-reported outcomes in a Swiss IBD cohort, we found that health care professionals seem to misinterpret patients' complaints. Patients self-rated GWB correlated with QoL scores, indicating that reporting GWB in a single question is possible and relevant, but can vary based on how the data are collected.

High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS: We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS: The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION: Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group--a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.

Long-Term Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: The FACTS III Survey.

BACKGROUND: Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. METHODS: In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. RESULTS: We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease (>5 years). CONCLUSIONS: CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.

Efficacy, Safety and Mucosal Healing of Methotrexate in a Large Longitudinal Cohort of Inflammatory Bowel Disease Patients.

BACKGROUND/AIMS: Evidence for the effectiveness of methotrexate (MTX) in treating inflammatory bowel disease (IBD) is still incomplete. This study assessed the effectiveness, safety and mucosal healing in IBD patients treated with MTX in the Swiss IBD Cohort. METHODS: Efficacy was defined by physician assessment or by CD activity index <150 points for Crohn's disease (CD) or Modified Truelove and Witts activity index <4 points for ulcerative colitis (UC), measured at least after 3 months of MTX therapy. Mucosal healing was evaluated after 3 months or more of therapy. RESULTS: MTX was administered to 341 patients (262 CD; 79 UC) out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0% (24/60) in UC (chi2 = 7.2409, p = 0.007). Among patients on MTX therapy at the time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD and UC patients respectively. The median duration of MTX therapy was 40 months for CD and 15 months for UC. Occurrence of adverse events was the first reason for treatment discontinuation (39.4% of all cases). The rate of mucosal healing with MTX was 9.5% for CD and 25% for UC patients respectively. CONCLUSION: MTX therapy was effective for the induction and maintenance therapy in IBD patients, with only a modest mucosal healing ability.

[Management of ulcerative colitis in 2017]. / Mise au point sur la rectocolite ulcéro-hémorragique en 2017.

Ulcerative colitis (UC) has a prevalence of 1 in 1000 inhabitants in Switzerland. The diagnosis of UC is based on a typical clinical presentation that involves bloody diarrhea, characteristic endoscopic features with continuous inflammation involving the rectum, and compatible histology. UC develops in genetically susceptible individuals with a dysregulated mucosal immune system. This article highlights latest insights into the pathogenesis, diagnosis, and therapy of UC.

La rectocolite ulcéro-hémorragique (RCUH) représente une maladie fréquente en Suisse avec une prévalence de 1 sur 1000 habitants. Le diagnostic se base sur la présentation clinique typique avec des diarrhées sanglantes, une image endoscopique caractéristique avec une inflammation continue qui touche pratiquement toujours le rectum, et une image histologique compatible. La RCUH se développe chez des individus avec prédisposition génétique et une dérégulation du système immunitaire colique. Cet article fait le point sur la pathogenèse, le diagnostic et les approches thérapeutiques de cette maladie.

Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents.

BACKGROUND & AIMS: Ustekinumab, a human monoclonal antibody against the p40 subunit of interleukins-12 and -23, is effective in inducing and maintaining remission in patients with luminal Crohn's disease (CD). We assessed the efficacy and safety of subcutaneous ustekinumab in patients with anti-tumor necrosis factor (anti-TNF) refractory CD. METHODS: We performed a retrospective observational study, collecting data from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif on 122 consecutive patients with active CD refractory to anti-TNF therapy who received at least 1 subcutaneous injection of ustekinumab from March 2011 to December 2014, in 20 tertiary centers in Europe. Subjects were followed for at least 3 months. The primary outcome was clinical benefit, defined as reductions in symptoms and biochemical markers of CD and complete weaning from steroids, without surgery or immunosuppressant therapies. RESULTS: Seventy-nine patients (65%) had a clinical benefit within 3 months of receiving ustekinumab. Concomitant immunosuppressant therapy at study inclusion increased the odds for a clinical benefit from ustekinumab (odds ratio, 5.43; 95% confidence interval, 1.14-25.77; P = .03). Over a median follow-up period of 9.8 months (interquartile range, 5.3-14.5 months), the cumulative probabilities that patients maintained the clinical benefit for 6 and 12 months after introduction of ustekinumab were 93% and 68%, respectively. CONCLUSIONS: Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent receive clinical benefit from ustekinumab therapy, not requiring steroids for up to 12 months afterward. While awaiting results from ongoing trials, ustekinumab can be considered for use in these patients.

Patients and gastroenterologists' perceptions of treatments for inflammatory bowel diseases: do their perspectives match?

BACKGROUND: Perceptions of appropriateness of treatments may differ between gastroenterologists (GIs) and inflammatory bowel disease (IBD) patients. The aim of this study was to explore and compare GIs' and patients' perceptions of risks and benefits of treatments and prioritization of expected outcomes. METHODS: Four vignette cases were drawn from clinical situations and used in three independent focus groups with GIs (n = 7), ulcerative colitis (UC-p, n = 8) and Crohn's disease patients (CD-p, n = 6). Content analysis was performed based on the conversation transcripts. RESULTS: UC-p agreed more often with GIs' treatment choices than CD-p. CD-p often considered 5-ASA as a placebo. UC-p saw topical 5-ASA as a temporary solution, neither comfortable nor practical when professionally active. Azathioprine was considered as the treatment for which the risks versus benefits were perceived as the highest. The main risk perceived by patients on anti-TNFs was a potential loss of response. Divergences were observed on 1) stop of treatment: UC-p did not easily concur with stopping a treatment, which differed from GIs' expectation of patients' perceptions; CD-p were more prone to consider stopping treatment than GIs, 2) perception of outcomes: physicians had a focus on long-term objective goals. Patients' expectations were of shorter term and mainly concerned stress management, nutritional advice, and information on the treatments effects. CONCLUSIONS: Overall, patients and GIs agreed on perceptions of IBD treatments. GIs seemed more concerned about objective and scientific measures of remission whereas patients focused on quality of life and social outcomes when it came to evaluating a therapy.

Characteristics of non-responders to self-reported questionnaires in a large inflammatory bowel disease cohort study.

BACKGROUND: A major threat to the validity of longitudinal cohort studies is non-response to follow-up, which can lead to erroneous conclusions. The objective of this study was to evaluate the profile of non-responders to self-reported questionnaires in the Swiss inflammatory bowel disease (IBD) Cohort. METHODS: We used data from adult patients enrolled between November 2006 and June 2011. Responders versus non-responders were compared according to socio-demographic, clinical and psychosocial characteristics. Odds ratio for non-response to initial patient questionnaire (IPQ) compared to 1-year follow-up questionnaire (FPQ) were calculated. RESULTS: A total of 1943 patients received IPQ, in which 331 (17%) did not respond. Factors inversely associated with non-response to IPQ were age >50 and female gender (OR = 0.37; p < 0.001 respectively OR = 0.63; p = 0.003) among Crohn's disease (CD) patients, and disease duration >16 years (OR = 0.48; p = 0.025) among patients with ulcerative colitis (UC). FPQ was sent to 1586 patients who had completed the IPQ; 263 (17%) did not respond. Risk factors of non-response to FPQ were mild depression (OR = 2.17; p = 0.003) for CD, and mild anxiety (OR = 1.83; p = 0.024) for UC. Factors inversely associated with non-response to FPQ were: age >30 years, colonic only disease location, higher education and higher IBD-related quality of life for CD, and age >50 years or having a positive social support for UC. CONCLUSIONS: Characteristics of non-responders differed between UC and CD. The risk of non-response to repetitive solicitations (longitudinal versus transversal study) seemed to decrease with age. Assessing non-respondents' characteristics is important to document potential bias in longitudinal studies.

Postsurgical Prophylaxis in Crohn's Disease: Which Patients, Which Agents?

Crohn's disease (CD) evolution is characterized by increasing proportions of patients developing complications such as strictures, abscesses and fistulas that require surgical management. After resection of a diseased intestinal segment, CD recurrence concerns up to 60% of patients within a year post surgery. The mucosa just above the site of the intestinal anastomosis is at particularly high risk of relapse. Prophylactic medical therapy to prevent recurrence has been shown to be effective with a variety of medications, but the recurrence rate remains high, demanding that a better risk stratification of patients be achieved. Recognized risk factors for postsurgical CD recurrence include young age at diagnosis and at surgery, smoking, need for repeated surgeries and penetrating disease. These patients require full dose immunosuppressive or anti-tumor necrosis factor (anti-TNF) therapy, which should be initiated in the immediate postoperative period, to prevent the onset of an inflammatory activity in the bowel. Systematic follow-up by endoscopy to monitor treatment benefit should also be part of the management, as endoscopic recurrence heralds clinical relapse in these patients. The role of noninvasive markers of mucosal inflammation, such as stool calprotectin levels, show promise to complete this monitoring. Although the efficacy of mesalazine and imidazole antibiotics has been long recognized, more aggressive approaches, such as thiopurines and anti-TNF antibodies, have shown higher efficacies in direct comparison trials. The potential place of anti-homing agents is not yet defined, but these agents should in principle be of interest for this prophylactic indication due to their mode of action and interesting side-effect profile. The current recommendations are based on a step-up approach that includes immunosuppressors and/or imidazole antibiotics, followed by an anti-TNF agent, such as infliximab and adalimumab, both already tested in randomized trials in this indication. When endoscopic recurrence is identified during follow-up, upscaling to anti-TNF or dose escalation is advocated.

Patients' information-seeking activity is associated with treatment compliance in inflammatory bowel disease patients.

BACKGROUND: Despite the chronic and relapsing nature of inflammatory bowel diseases (IBD), at least 30% to 45% of the patients are noncompliant to treatment. IBD patients often seek information about their disease. AIM: To examine the association between information-seeking activity and treatment compliance among IBD patients. To compare information sources and concerns between compliant and noncompliant patients. METHODS: We used data from the Swiss IBD cohort study, and from a qualitative survey conducted to assess information sources and concerns. Crude and adjusted odds ratios (OR) for noncompliance were calculated. Differences in the proportions of information sources and concerns were compared between compliant and noncompliant patients. RESULTS: A total of 512 patients were included. About 18% (n = 99) of patients were reported to be noncompliant to drug treatment and two-thirds (n = 353) were information seekers. The OR for noncompliance among information seekers was 2.44 (95%CI: 1.34-4.41) after adjustment for confounders and major risk factors. General practitioners were 15.2% more often consulted (p = 0.019) among compliant patients, as were books and television (+13.1%; p = 0.048), whereas no difference in proportions was observed for sources such as internet or gastroenterologists. Information on tips for disease management were 14.2% more often sought among noncompliant patients (p = 0.028). No difference was observed for concerns on research and development on IBD or therapies. CONCLUSION: In Switzerland, IBD patients noncompliant to treatment were more often seeking disease-related information than compliant patients. Daily management of symptoms and disease seemed to be an important concern of those patients.

Critical role of the GM-CSF signaling pathway in macrophage pro-repair activities.

OBJECTIVE: Macrophages play a critical role in intestinal wound repair. However, the molecular pathways that regulate macrophage wound repair activities remain poorly understood. The aim of this study was to evaluate the role of GM-CSF receptor signaling in the wound repair activities of macrophages. METHODS: Murine macrophages were differentiated from bone marrow cells and human macrophages from monocytes isolated from peripheral blood mononuclear cells of Crohn's disease (CD) patients. In vitro models were used to study the repair activities of macrophages. RESULTS: We provide evidence that GM-CSF receptor signaling is required for murine macrophages to promote epithelial repair. In addition, we demonstrate that the deficient repair properties of macrophages from CD patients with active disease can be recovered via GM-CSF therapy. CONCLUSION: Our data support a critical role of the GM-CSF signaling pathway in the pro-repair activities of mouse and human macrophages.

Monitoring disease activity and progression in Crohn's disease. A Swiss perspective on the IBD ahead 'optimised monitoring' recommendations.

BACKGROUND AND AIMS: The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. METHODS: The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. RESULTS: A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. CONCLUSION: The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations.