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ABSTRACT: BACKGROUND:: Using clinical symptoms alone to inform treatment decisions in Crohn's disease (CD) may increase the risk of disease progression and complications. Treatment beyond symptoms may offer improved outcomes. METHODS:: We explore alternative definitions of remission, beyond traditional clinical remission, incorporating more objective parameters of inflammation control, which may support prevention or delay the disease progression. These definitions could serve as a platform for future clinical research, evaluating whether treating beyond symptoms alters the natural history of CD. RESULTS:: Proposed definitions may include endoscopic remission (mucosal healing), normalization of serologic or fecal markers of inflammation, and even radiographic remission, in addition to clinical remission (symptom control). Endoscopic remission is the leading candidate for inclusion because it is the best studied. The definition should include considerations for both early and late disease given that in late disease, which may be associated with operation-related symptoms or irreversible bowel damage, symptomatic remission may not achievable. Desired outcomes in early disease are complete absence of symptoms, no disease progression, no complications or disability, and normal quality of life. In late disease, there are stabilization of noninflammatory symptoms, no progression of damage or disability, and improved quality of life. CONCLUSIONS:: Over time, we anticipate that a working definition of remission that includes both biological remission and clinical remission will evolve and be evaluated in clinical trials. Our proposed definition is a possible starting point for that evolution. Ultimately, the goal in evolving the definition of remission is to improve the outcomes in patients with CD.
Inflammatory Bowel Diseases 04/2013; · 4.86 Impact Factor
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Pavol Papay,
Ana Ignjatovic,
Konstantinos Karmiris,
Heda Amarante,
Pal Milheller,
Brian Feagan,
Geert D'Haens,
Philippe Marteau,
Walter Reinisch,
Andreas Sturm,
Flavio Steinwurz,
Laurence Egan,
Julián Panés, Edouard Louis,
Jean-Frédéric Colombel,
Remo Panaccione
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ABSTRACT: Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation can be disconnected. Therefore, strategies that objectively monitor inflammatory activity should be utilised throughout the disease course to optimise patient management. Initially, a thorough assessment of the severity, location and extent of disease is needed to ensure a correct diagnosis, identify any complications, help assess prognosis and select appropriate therapy. During follow-up, clinical decision-making should be driven by disease activity monitoring, with the aim of optimising treatment for tight disease control. However, few data exist to guide the choice of monitoring tools and the frequency of their use. Furthermore, adaption of monitoring strategies for symptomatic, asymptomatic and post-operative patients has not been well defined. The Annual excHangE on the ADvances in Inflammatory Bowel Disease (IBD Ahead) 2011 educational programme, which included approximately 600 gastroenterologists from 36 countries, has developed practice recommendations for the optimal monitoring of Crohn's disease based on evidence and/or expert opinion. These recommendations address the need to incorporate different modalities of disease assessment (symptom and endoscopic assessment, measurement of biomarkers of inflammatory activity and cross-sectional imaging) into robust monitoring. Furthermore, the importance of measuring and recording parameters in a standardised fashion to enable longitudinal evaluation of disease activity is highlighted.
Journal of Crohn s and Colitis 04/2013; · 2.57 Impact Factor
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Gert Van Assche,
Karin A Herrmann, Edouard Louis,
Simon M Everett,
Jean-Frédéric Colombel,
Jean-François Rahier,
Dirk Vanbeckevoort,
Paul Meunier,
Damian Tolan,
Olivier Ernst,
Paul Rutgeerts,
Séverine Vermeire,
Isolde Aerden,
Alessandra Oortwijn,
Thomas Ochsenkühn
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ABSTRACT: BACKGROUND AND AIMS: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy. METHODS: In this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease. RESULTS: Twenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by ≥2 points and by ≥50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index. CONCLUSION: Improvement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare.
Journal of Crohn s and Colitis 02/2013; · 2.57 Impact Factor
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Laurent Peyrin-Biroulet,
Vincent Billioud,
Geert D'Haens,
Remo Panaccione,
Brian Feagan,
Julian Panés,
Silvio Danese,
Stefan Schreiber,
Haruhiko Ogata,
Toshifumi Hibi,
Peter D R Higgins,
Laurent Beaugerie,
Yehuda Chowers, Edouard Louis,
Flávio Steinwurz,
Walter Reinisch,
Paul Rutgeerts,
Jean-Frédéric Colombel,
Simon Travis,
William J Sandborn
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ABSTRACT: We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD.
The American Journal of Gastroenterology 12/2012; 107(12):1770-6. · 7.28 Impact Factor
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Luke Jostins,
Stephan Ripke,
Rinse K Weersma,
Richard H Duerr,
Dermot P McGovern,
Ken Y Hui,
James C Lee,
L Philip Schumm,
Yashoda Sharma,
Carl A Anderson, [......],
Graham Radford-Smith,
Christopher G Mathew,
John D Rioux,
Eric E Schadt,
Mark J Daly,
Andre Franke,
Miles Parkes,
Severine Vermeire,
Jeffrey C Barrett,
Judy H Cho
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ABSTRACT: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
Nature 11/2012; 491(7422):119-24. · 36.28 Impact Factor
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ABSTRACT: BACKGROUND AND AIMS: Patients' and physicians' perceptions of ulcerative colitis and its management are important for developing and guiding appropriate therapies. This study explored national differences in patients' and physicians' experiences, expectations, and beliefs about ulcerative colitis. METHODS: Structured, cross-sectional, online surveys evaluating various indices were completed by 775 adult patients with ulcerative colitis and 475 physicians actively managing ulcerative colitis patients from France, Germany, Ireland, Spain, the United Kingdom, and Canada. RESULTS: Patients' classification of their symptom severity differed across countries (mild, 16%-45%; moderate, 46%-58%; severe, 4%-36%). Expectations of disease control also varied, with 26% (Ireland) to 65% (Spain) describing that remission realistically involves "living without symptoms." Within each country, more patients (45%-69%) than physicians (28%-45%) considered ulcerative colitis symptoms to affect patients' quality of life. Mean number of patient-reported flares during the past year ranged from 2.5 in Ireland to 8.0 in France. Self-reported adherence with oral 5-aminosalicylic acid (during remission) was highest in Spain (91% vs 50%-73% across other countries). Spanish patients were more likely to self-adjust their medications (54% vs 2%-5%), but reported the most dissatisfaction with therapy (42% vs 9%-27%). Irish patients were least likely to arrange physician/specialist nurse visits (14% vs 36%-49%) and least open to discussion of their condition. CONCLUSIONS: Important national differences in ulcerative colitis patients' attitudes and perceptions were observed, which may help physicians improve patient care based on country-specific needs and influence self-assessments in clinical trials. The results suggest a need for structured patient education to improve adherence and outcomes.
Journal of Crohn s and Colitis 08/2012; · 2.57 Impact Factor
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ABSTRACT: BACKGROUND: The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and healthcare professionals (HCPs). METHODS: Structured, cross-sectional, Web-based questionnaires designed to assess a variety of disease indices were completed by adult patients with UC and HCPs involved in the care of patients with UC from Canada, France, Germany, Ireland, Spain, and the United Kingdom. RESULTS: Surveys were completed by 775 patients, 475 physicians, and 50 nurses. Patient self-reported classification of disease severity revealed generally greater severity (mild, 32 %; moderate, 53 %) compared with physician and nurse estimates of UC severity among their caseloads (mild, 52 % and 49 %; moderate, 34 % and 37 %, respectively). Patients reported that an average of 5.5 (standard deviation, 11.0) flares (self-defined) occurred over the past year, compared with 3.4 and 3.8 flares per year estimated by physicians and nurses. Perceived flare triggers differed between patients (stress ranked first) and HCPs (natural disease course ranked first). Fifty-five percent of patients stated that UC symptoms over the past year had affected their quality of life, while physicians and nurses estimated that 35 % to 37 % of patients would have a reduced quality of life over the same period. Patients ranked urgency and pain as the most bothersome symptoms, while physicians and nurses ranked urgency and stool frequency highest. About half of patients (47 %) defined remission as experiencing no symptoms; by comparison, 62 % to 63 % of HCPs defined remission as requiring the complete absence of symptoms. HCPs (doctors/nurses in general practice and/or hospital) were regarded by patients as their main source of UC information by 72 %; however, 59 % reported not arranging regular visits to see their HCPs. CONCLUSIONS: This large survey identified important differences between patients' and HCPs' perceptions of the impact of UC symptoms on patients' lives. Notably, HCPs may underestimate the effect of specific UC symptoms on patients and may fail to recognize issues that are important to patients.
BMC Gastroenterology 08/2012; 12(1):108. · 2.42 Impact Factor
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ABSTRACT: Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures, fistulae, perianal complications, surgery, and colorectal cancer. Changing the natural history and avoiding evolution to a disabling disease should be the main goal of treatment. In recent studies, mucosal healing has been associated with longer-term remission and fewer complications. Conventional therapies with immunosuppressive drugs are able to induce mucosal healing in a minority of cases but their impact on disease progression appears modest. Higher rates of mucosal healing can be achieved with anti-tumor necrosis factor therapies that reduce the risk of relapse, surgery and hospitalization, and are associated with perianal fistulae closure. These drugs might be able to change the natural history of the disease mainly when introduced early in the course of the disease. Treatment strategy in inflammatory bowel diseases should thus be tailored according to the risk that each patient could develop disabling disease.
World Journal of Gastroenterology 08/2012; 18(29):3823-7. · 2.47 Impact Factor
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ABSTRACT: Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients' family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations. This article aims to provide a framework for clinical decision making in IBD based on review of the literature on pregnancy-related topics.
Medline searches with search terms 'IBD', 'Crohn's disease' or 'ulcerative colitis' in combination with keywords for the topics fertility, pregnancy, congenital abnormalities and drugs names of drugs used for treatment of IBD.
IBD patients have normal fertility, except for women after ileal pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving and maintaining disease remission is a key factor for successful pregnancy outcomes in this population, as active disease at conception carries an increased risk of preterm delivery and low birth weight. Clinicians should discuss the need for drug therapy to maintain remission with their patients in order to ensure therapy compliance. Most IBD drugs are compatible with pregnancy, except for methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by the end of the second trimester and the choice of delivery route should be discussed with the patient.
Disease control prior to conception and throughout pregnancy is the cornerstone of successful pregnancy management in IBD patients.
Journal of Crohn s and Colitis 05/2012; 6(8):811-23. · 2.57 Impact Factor
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ABSTRACT: BACKGROUND AND AIMS: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. METHODS: All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome. RESULTS: Eighty four percent of 720 patients had a primary response and were followed up for a median of 14months. Thirty four percent needed escalation after a median of 7months (0-55months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14m adalimumab was discontinued in 29% of patients. CONCLUSION: In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab.
Journal of Crohn s and Colitis 04/2012; · 2.57 Impact Factor
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Gastroenterology 11/2011; 142(1):176-8. · 11.68 Impact Factor
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Marco Daperno,
Fabiana Castiglione,
Lissy de Ridder,
Iris Dotan,
Martti Färkkilä,
Jon Florholmen,
Gerald Fraser,
Walter Fries,
Xavier Hebuterne,
Peter Laszlo Lakatos,
Julián Panés,
Jordi Rimola, Edouard Louis
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ABSTRACT: The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing both in clinical studies and routine practice is a key issue. Endoscopy for the colon and terminal ileum and computerized tomography or magnetic resonance imaging for the small bowel are the most direct ways to evaluate intestinal healing. However, there are many unsolved questions about the definition and the precise assessment of intestinal healing using these endoscopic and imaging techniques. Furthermore, these are relatively invasive and expensive procedures that may be inadequate for regular patients' monitoring. Therefore, biomarkers such as C-reactive protein and fecal calprotectin have been proposed as surrogate markers for intestinal healing. Nevertheless, the sensitivity and specificity of these markers for the prediction of healing may be insufficient for routine practice. New stool, blood or intestinal biomarkers are currently studied and may improve our ability to monitor intestinal healing in the future.
Journal of Crohn s and Colitis 10/2011; 5(5):484-98. · 2.57 Impact Factor
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Edouard Louis,
Jean-Yves Mary,
Gwenola Vernier-Massouille,
Jean-Charles Grimaud,
Yoram Bouhnik,
David Laharie,
Jean-Louis Dupas,
Hélène Pillant,
Laurence Picon,
Michel Veyrac,
Mathurin Flamant,
Guillaume Savoye,
Raymond Jian,
Martine Devos,
Raphaël Porcher,
Gilles Paintaud,
Eric Piver,
Jean-Frédéric Colombel,
Marc Lemann
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ABSTRACT: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse.
We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model.
After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% ± 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 × 10(9)/L, and levels of hemoglobin ≤145 g/L, C-reactive protein ≥5.0 mg/L, and fecal calprotectin ≥300 μg/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse.
Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.
Gastroenterology 09/2011; 142(1):63-70.e5; quiz e31. · 11.68 Impact Factor
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ABSTRACT: It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.
Rheumatology (Oxford, England) 09/2011; 50(11):1955-68. · 4.24 Impact Factor
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Benjamin Pariente,
Jacques Cosnes,
Silvio Danese,
William J Sandborn,
Maïté Lewin,
Joel G Fletcher,
Yehuda Chowers,
Geert D'Haens,
Brian G Feagan,
Toshifumi Hibi, [......],
Bruce E Sands,
Juergen Schoelmerich,
Stefan Schreiber,
Herbert Tilg,
Simon Travis,
Gert van Assche,
Maurizio Vecchi,
Jean-Yves Mary,
Jean-Frédéric Colombel,
Marc Lémann
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ABSTRACT: Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.
Inflammatory Bowel Diseases 06/2011; 17(6):1415-22. · 4.86 Impact Factor
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Inflammatory Bowel Diseases 04/2011; 17(6):E62-3. · 4.86 Impact Factor
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ABSTRACT: Inflammatory bowel diseases (IBD) are classically divided in Crohn's disease (CD) and ulcerative colitis (UC). However, these two entities are still heterogeneous and a further classification in subphenotypes is necessary. Clinical subphenotypes are easy to use, do not necessitate complicated tests and can already give very important information for the management of the patients. In CD, clinical subphenotypes are based on age at diagnosis, disease location and disease behaviour. Age at diagnosis allows to differentiating paediatric CD, classical young adult onset and more seldom CD of the elderly. These categories are associated with a different risk of development of complications and disabling disease and may have partly different pathophysiology. The classification on disease behaviour, including stricturin, penetrating or uncomplicated disease may have an impact on reponse to medical treatment and need for surgery. Finally the classification based on location is particularly relevant since it has been associated with different types of complications. Particularly ileal disease has been associated with the risk of surgery and colonic (particularly rectal) disease, with the risk of perianal disease. In UC, the classification in subphenotypes is essentially based on disease location, distinguishing proctitis, left-sided colitis and extensive colitis. This subclassification also has a very significant clinical relevance since extensive colitis has been associated with and increased risk of colon cancer, colectomy and even in some studies, mortality.
Best practice & research. Clinical gastroenterology 04/2011; 25 Suppl 1:S2-7. · 2.48 Impact Factor
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Jean-François Rahier,
Pavol Papay,
Julia Salleron,
Shaji Sebastian,
Manuela Marzo,
Laurent Peyrin-Biroulet,
Valle Garcia-Sanchez,
Walter Fries,
Dirk P van Asseldonk,
Klaudia Farkas, [......],
Taina Sipponen,
Pierre Ellul, Edouard Louis,
Simon T C Peake,
Uri Kopylov,
Jochen Maul,
Badira Makhoul,
Gionata Fiorino,
Yazdan Yazdanpanah,
Maria Chaparro
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ABSTRACT: Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy.
The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded.
Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%).
Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.
Gut 02/2011; 60(4):456-62. · 10.11 Impact Factor
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Carl A Anderson,
Gabrielle Boucher,
Charlie W Lees,
Andre Franke,
Mauro D'Amato,
Kent D Taylor,
James C Lee,
Philippe Goyette,
Marcin Imielinski,
Anna Latiano, [......],
Mark J Daly,
Jeffrey C Barrett,
Miles Parkes,
Vito Annese,
Hakon Hakonarson,
Graham Radford-Smith,
Richard H Duerr,
Séverine Vermeire,
Rinse K Weersma,
John D Rioux
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ABSTRACT: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
Nature Genetics 02/2011; 43(3):246-52. · 35.53 Impact Factor
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Dominique de Seny,
Mohammed Sharif,
Marianne Fillet,
Gaël Cobraiville,
Marie-Alice Meuwis,
Raphaël Marée,
Jean-Philippe Hauzeur,
Louis Wehenkel, Edouard Louis,
Marie-Paule Merville,
John Kirwan,
Clio Ribbens,
Michel Malaise
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ABSTRACT: Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specificity and sensitivity. Therefore, novel biomarkers are needed to better understand the pathophysiological processes of OA initiation and progression.
Surface enhanced laser desorption/ionisation-time of flight-mass spectrometry proteomic technique was used to analyse protein expression levels in 284 serum samples from patients with knee OA classified according to Kellgren and Lawrence (K&L) score (0-4). OA serum samples were also compared to serum samples provided by healthy individuals (negative control subjects; NC; n=36) and rheumatoid arthritis (RA) patients (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, whereas proteins with increased or decreased levels of expression were selected for further studies.
Two proteins were found to be expressed at higher levels in sera of OA patients at all four K&L scores compared to NC and RA, and were identified as V65 vitronectin fragment and C3fpeptide. Of the two remaining proteins, one showed increased expression (unknown protein at m/z of 3762) and the other (identified as connective tissue-activating peptide III protein) was decreased in K&L scores >2 subsets compared to NC, RA and K&L scores 0 or 1 subsets.
The authors detected four unexpected biomarkers (V65 vitronectin fragment, C3f peptide, CTAP-III and m/z 3762 protein) that could be relevant in the pathophysiological process of OA as having significant correlation with parameters reflecting local inflammation and bone remodelling, as well as decrease in cartilage turnover.
Annals of the rheumatic diseases 02/2011; 70(6):1144-52. · 8.11 Impact Factor
