J Panés

University Pompeu Fabra, Barcino, Catalonia, Spain

Are you J Panés?

Claim your profile

Publications (353)2610 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe endoscopic lesions (SEL) in patients with colonic Crohn's disease (CD) have been linked to higher risk of colectomy. The aims of this study were to reassess the predictive value of colonoscopy compared against MRI for requirement of resection surgery in patients with CD and determine the influence of current therapeutic options. In this single-centre, observational, prospective, longitudinal study, patients with an established diagnosis of CD and suspected activity were included. After baseline assessment, including colonoscopy and MRI, patients were followed until resection surgery or the end of study. 112 patients were eligible for analysis. Ulcers were present in 94/112 (84%) of patients at colonoscopy (SELs in 51/112 (46%)) and stenosis in 38/112 (34%). MRI identified ulcers in 79/112 (71%) of patients, stenosis in 36/112 (32%) and intra-abdominal fistulae in 20/112 (18%). Surgical resection requirements (29/112 (26%)) were not associated with the presence of SELs at colonoscopy. The presence of stenosis (p<0.001) or intra-abdominal fistulae (p<0.001) at MRI correlated with a higher risk of surgery. In the multivariate analysis, perianal disease (OR 9 (2 to 39), p=0.003), stenosis (OR 3.4 (1 to 11), p=0.04) and fistulae at MRI (OR 10.6 (2 to 46), p=0.002) increased the risk of abdominal resection surgery, while months under immunomodulators (OR 0.94 (0.90 to 0.98), p=0.002) and/or antitumor necrosis factor (anti-TNF) therapy (OR 0.97 (0.94 to 1), p=0.04) during follow-up decreased this risk. Perianal disease, stenosis and/or intra-abdominal fistulae at MRI independently predict an increased risk of resection surgery in patients with CD, whereas immunosuppressants and/or anti-TNF therapy reduce such risk. Under current therapeutic strategies, the presence of SELs is not a predictor of resection surgery in patients with CD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 12/2014; · 10.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: & Aims: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, that measures disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD).
    Gastroenterology 09/2014; · 12.82 Impact Factor
  • Silvio Danese, Julián Panés
    [Show abstract] [Hide abstract]
    ABSTRACT: Increased understanding of the pathogenesis of inflammatory bowel diseases (IBD) has led to new therapeutic strategies. One of these is to target the molecules that regulate interactions between leukocytes and endothelial cells at sites of inflammation (mainly leukocyte integrins and endothelial cell adhesion molecules of the immunoglobulin superfamily). These molecules have been validated as therapeutic targets for IBD; several have shown efficacy and 2 have been approved by the Food and Drug Administration for treatment of IBD. Natalizumab, the first anti-integrin antibody tested for treatment of IBD, blocks the α4 subunit. Although it is effective, its clinical use has been limited by its association with risk for progressive multifocal leukoenkephalopathy. Other, allegedly more selective, drugs that affect leukocyte recruitment in the gastrointestinal tract have been developed or are under investigation, and could increase safety. These include vedolizumab and AMG 181 (antibodies against α4β7), etrolizumab (anti-β7), and PF-00547659 (anti-mucosal vascular addressin cell adhesion molecule 1). Other agents have been developed to block α4 (the small molecule AJM300), CCR9 (the small molecule CCX282-B), and CXCL10 (the antibody eldelumab). We review the scientific rationale for inhibiting interactions between leukocytes and endothelial cells to reduce intestinal inflammation, and analyze the clinical studies that have been carried out to test these new molecules, with particular attention to safety. We propose an evidence-based clinical positioning of this class of drugs.
    Gastroenterology 09/2014; · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dersalazine sodium is an inhibitor of platelet activator factor with potential efficacy in patients with ulcerative colitis through an alternative mechanism of action. The study was a first proof of clinical safety and activity of dersalazine sodium in patients with ulcerative colitis.
    Inflammatory Bowel Diseases 09/2014; · 5.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & Aims Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through γ-chain–containing cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn’s disease. Methods Patients (n = 139, ≥18 y old) with moderate-to-severe active Crohn’s disease were randomly assigned to groups given 1 mg (n=36), 5 mg (n=34), or 15 mg (n=35) tofacitinib or placebo (n=34), twice daily for 4 weeks, at 48 centers in 12 countries. The primary endpoint was the proportion of clinical responders at week 4 (decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥70 points [Response-70]). Secondary endpoints included clinical remission (CDAI score <150 points) at week 4. Results A clinical response was observed in 36% (P = .467), 58% (P = .466), and 46% (P ≥ .999) of patients given the 1, 5, and 15 mg doses of tofacitinib, compared with 47% of patients given placebo. Clinical remission was observed in 31% (P = .417), 24% (P = .776), and 14% (P = .540) of patients given the 1, 5, and 15 mg doses of tofacitinib, compared with 21% of patients given placebo. The 15 mg dose of tofacitinib reduced levels, from baseline, of C-reactive protein and fecal calprotectin. Adverse and serious adverse events were similar among groups. Dose-dependent increases in low- and high-density lipoprotein cholesterol were observed in patients given the 5 or 15 mg doses of tofacitinib. Conclusions There were no significant differences in percentages of patients with moderate-to-severe active Crohn’s disease who achieved clinical responses (Response-70) or clinical remission following 4 weeks administration of tofacitinib (1, 5, or 15 mg) or placebo twice daily. However, a large percentage of patients given placebo achieved Response-70 or remission. Reductions in C-reactive protein and fecal calprotectin among patients given the 15 mg dose of tofacitinib indicate its biologic activity. ClinicalTrials.gov Number NCT00615199.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2014; · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1,525 healthy controls from Spain with the six previously published GWAS comprising 6,687 cases and 19,718 controls from Northern European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 (rs2858829, P=8.97 x 10(-9), OR (95% CI)=1.12 (1.08-1.16)) that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1,073 cases and 1,279 controls (combined P=7.59 x 10(-10), OR (95% CI)=1.12 (1.08-1.16)). Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P<0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence.
    Gut 06/2014; · 10.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine the accuracy of advanced endoscopy for prediction of relapse in ulcerative colitis, in comparison with serum and fecal biomarkers.
    Inflammatory Bowel Diseases 05/2014; · 5.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of the heterodimeric integrins α4β7 and αEβ7. We aimed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis. In this double-blind, placebo-controlled, randomised, phase 2 study, patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries. Eligible patients (aged 18-75 years; Mayo Clinic Score [MCS] of 5 of higher [or ≥6 in USA]; and disease extending 25 cm or more from anal verge) were randomised (1:1:1) to one of two dose levels of subcutaneous etrolizumab (100 mg at weeks 0, 4, and 8, with placebo at week 2; or 420 mg loading dose [LD] at week 0 followed by 300 mg at weeks 2, 4, and 8), or matching placebo. The primary endpoint was clinical remission at week 10, defined as MCS of 2 or less (with no individual subscore of >1), analysed in the modified intention-to-treat population (mITT; all randomly assigned patients who had received at least one dose of study drug, had at least one post-baseline disease-activity assessment, and had a centrally read screening endoscopic subscore of ≥2). This study is registered with ClinicalTrials.gov, number NCT01336465. Between Sept 2, 2011, and July 11, 2012, 124 patients were randomly assigned, of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population, leaving 39 patients in the etrolizumab 100 mg group, 39 in the etrolizumab 300 mg plus LD group, and 41 in the placebo group for the primary analyses. No patients in the placebo group had clinical remission at week 10, compared with eight (21% [95% CI 7-36]) patients in the etrolizumab 100 mg group (p=0·0040) and four (10% [0·2-24]) patients in the 300 mg plus LD group (p=0·048). Adverse events occurred in 25 (61%) of 41 patients in the etrolizumab 100 mg group (five [12%] of which were regarded as serious), 19 (48%) of 40 patients in the etrolizumab 300 mg plus LD group (two [5%] serious), and 31 (72%) of 43 patients in the placebo group (five [12%] serious). Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo. Therefore, blockade of both α4β7 and αEβ7 might provide a unique therapeutic approach for the treatment of ulcerative colitis, and phase 3 studies have been planned. Genentech.
    The Lancet 05/2014; · 39.21 Impact Factor
  • Source
    Journal of Crohn s and Colitis 05/2014; · 3.39 Impact Factor
  • Gastroenterology 05/2014; 8:S7. · 12.82 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-586. · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It goes back to 1932 when Dr. Burrill Bernard Crohn and co-workers published their landmark paper, describing regional ileitis as a disease entity. However, clinical trial research has been developing rather slowly in luminal Crohn's disease. It took until the early seventies before the first randomized clinical trial was set up by the National Co-operative Crohn's Disease Study (NCCDS) group. Although the efforts of this group triggered a first wave of clinical trials in Crohn's disease, the lack of guidelines for conducting a clinical trial in this research area resulted in a variety of study designs and much criticism. Besides having a rather small sample size and a short follow-up time, they were often characterized by vague and subjective assessment of disease activity and treatment response. Following the advent of a new and very potent drug class in the late nineties, the anti-TNF agents, investigators started to re-think their study protocols and the first guidelines were set up by the regulatory authorities. Over the last 15 years, clinical trials in luminal Crohn's disease have been evolving significantly. Inclusion criteria have been shifting from clinical scores such as Crohn's Disease Activity Index (CDAI) to more objective disease activity parameters such as biomarkers (C-reactive protein and faecal calprotectin) and endoscopic lesions. Primary endpoints have been developing from clinical response to corticosteroid-free remission and more ambitious end-points such as mucosal healing. In this paper, we will give a historical overview on clinical trials in luminal Crohn's disease, before and within the biologic era, and provide insight into how they have shaped our current understanding of trial designs in Crohn's disease.
    Journal of Crohn s and Colitis 05/2014; · 3.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment goals in inflammatory bowel diseases are evolving beyond the control of symptoms towards the tight control of objectively-measured gastrointestinal inflammation. This review discusses the progress and challenges in adopting a treat-to-target approach in inflammatory bowel diseases. Evidence from the literature that highlights current thinking in terms of treating-to-target in patients with inflammatory bowel diseases is discussed. Monitoring for objective evidence of inflammation using endoscopy, cross-sectional imaging or laboratory biomarkers may be a useful approach in inflammatory bowel diseases; however, setting the appropriate treatment goal remains a challenge. Deep remission (a composite of symptom control and mucosal healing) may now be a realistic target in Crohn's disease; however, it remains to be proven that achieving deep remission will modify the long-term disease course. Assessing prognosis at an early stage of the disease course is essential for the development of an appropriate management plan, with the rationale of adapting treatment to disease severity. An algorithm has been proposed for the treatment of early Crohn's disease that involves early treatment with immunosuppressants and tumour necrosis factor antagonists, in the hope of preventing structural bowel damage. Treating beyond symptoms will require a clear management plan influenced by disease severity at presentation, clinical and biological prognostic factors, achievement and maintenance of clinical and biological remission and pharmacoeconomics.
    Journal of Crohn s and Colitis 04/2014; · 3.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are a number of gaps in our current quality of care for patients with inflammatory bowel diseases. This review proposes changes that could be made now to improve inflammatory bowel disease care. Evidence from the literature and clinical experience are presented that illustrate best practice for improving current quality of care of patients with inflammatory bowel diseases. Best care for inflammatory bowel disease patients will involve services provided by a multidisciplinary team, ideally delivered at a centre of excellence and founded on current guidelines. Dedicated telephone support lines, virtual clinics and networking may also provide models through which to deliver high-quality, expert integrated patient care. Improved physician-patient collaboration may improve treatment adherence, producing tangible improvements in disease outcomes, and may also allow patients to better understand the benefits and risks of a disease management plan. Coaching programmes and tools that improve patient self-management and empowerment are likely to be supported by payers if these can be shown to reduce long-term disability. Halting disease progression before there is widespread bowel damage and disability are ideal goals of inflammatory bowel disease management. Improving patient-physician communication and supporting patients in their understanding of the evidence base are vital for ensuring patient commitment and involvement in the long-term management of their condition. Furthermore, there is a need to create more centres of excellence and to develop inflammatory bowel disease networks to ensure a consistent level of care across different settings.
    Journal of Crohn s and Colitis 04/2014; · 3.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anti-tumour necrosis factor α (TNFα) therapy effectively induces and maintains remission in Crohn's disease (CD). Up to 40% of patients, however, fail to respond to anti-TNFα. To identify the mechanisms underlying the persistence of mucosal lesions in patients who fail to respond to anti-TNFα therapy. An observational study based on whole-genome transcriptional analysis was carried out using intestinal biopsy specimens from patients with CD receiving (n=12) or not (n=10) anti-TNFα therapy. The transcriptional signature of responders was compared with that of non-responders after anti-TNFα therapy. Controls with non-inflammatory bowel disease (non-IBD) (n=17) were used for comparisons. Genes of interest were validated by real-time RT-PCR in an independent cohort of patients with CD receiving (n=17) or not (n=16) anti-TNFα and non-IBD controls (n=7). We confirmed that response to anti-TNFα is accompanied by significant regulation of a large number of genes, including IL1B, S100A8, CXCL1, which correlated with endoscopic activity. Remarkably, patients who failed to respond to anti-TNFα showed a mixed signature, maintaining increased expression of IL1B, IL17A and S100A8, while showing significant modulation of other genes commonly upregulated in active CD, including IL6 and IL23p19. Our results show that anti-TNFα therapy significantly downregulates a subset of inflammatory genes even in patients who fail to achieve endoscopic remission, suggesting that these genes may not be dominant in driving inflammation in non-responders. On the other hand, we identified IL1B and IL17A as genes that remained altered in non-responders, pointing to potentially more relevant targets for modulating mucosal damage in refractory patients.
    Gut 04/2014; · 10.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. Aim To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. Methods 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. Results In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25–44] vs 37 years [IQR 27–49]; p < 0.0001); (CD: 27 years [IQR 21–35] vs 29 years [IQR 22–40]; p < 0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p = 0.04); (CD: 30.1% vs 23.6%; p < 0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p = 0.0001), penetrating behavior (21% vs 17.6%; p = 0.01) and perianal disease (32% vs 27.1%; p = 0.003). Differences are not influenced by degree of consanguinity. Conclusion When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.
    Journal of Crohn s and Colitis 03/2014; 8(3):234–239. · 3.39 Impact Factor
  • Article: Reply.
    Julián Panés, Antonio López-Sanromán
    Gastroenterology 03/2014; 146(3):869-70. · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND AIMS: While it is commonly accepted that Inflammatory bowel disease (IBD) Comprehensive Care Units (ICCUs) facilitate the delivery of quality care to Crohn's disease and ulcerative colitis patients, it remains unclear how an ICCU should be defined or evaluated. The aim of the present study was to develop a comprehensive set of Quality Indicators (QIs) of structure, process, and outcomes for defining and evaluating an ICCU. METHODS: A Delphi consensus-based approach with a standardized three-step process was used to identify a core set of QIs. The process included an exhaustive search using complementary approaches to identify potential QIs, and two Delphi voting rounds to select the QIs defining the core requirements for an ICCU. RESULTS: The consensus selected a core set of 56 QIs (12 structure, 20 process and 24 outcome). Structure and process QIs highlighted the need for multidisciplinary management and continuity of care. The minimal IBD team should include an IBD nurse, gastroenterologists, radiologists, surgeons, endoscopists and stoma management specialists. ICCUs should be able to provide both outpatient and inpatient care and admission should not break the continuity of care. Outcome QIs focused on the adequate prophylaxis of disease complication and drug adverse events, the need to monitor appropriateness of treatment and the need to reinforce patient autonomy by providing adequate information and facilitating the patients' participation in their own care. CONCLUSIONS: The present Delphi consensus identified a set of core QIs that may be useful for evaluating and certifying ICCUs.
    Journal of Crohn s and Colitis 03/2014; J Crohns Colitis. 2014 Mar 1;8(3):240-251.. · 3.39 Impact Factor
  • Julian Panes
    Journal of Crohn's and Colitis. 01/2014;

Publication Stats

7k Citations
2,610.00 Total Impact Points


  • 2014
    • University Pompeu Fabra
      Barcino, Catalonia, Spain
  • 1994–2014
    • Hospital Clínic de Barcelona
      • Servicio de Gastroenterología
      Barcino, Catalonia, Spain
  • 1992–2014
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2013
    • Azienda Ospedaliera Fatebenefratelli e Oftalmico Milano
      Milano, Lombardy, Italy
  • 2012–2013
    • Medical University of Vienna
      Wien, Vienna, Austria
    • Hospital Universitari Sant Joan de Reus
      Reus, Catalonia, Spain
    • University of Leuven
      Louvain, Flanders, Belgium
    • University of California, San Diego
      • Division of Gastroenterology
      San Diego, CA, United States
    • Centro Medico Teknon
      Barcino, Catalonia, Spain
  • 2009–2013
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
    • Hospital Clínico, Maracaibo
      Maracaibo, Estado Zulia, Venezuela
    • Hospital Posadas
      Buenos Aires, Buenos Aires F.D., Argentina
  • 1999–2013
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2011
    • Centre Hospitalier Universitaire de Liège
      Luik, Walloon Region, Belgium
  • 2009–2011
    • Hospital Universitario de La Princesa
      • Servicio de Aparato Digestivo
      Madrid, Madrid, Spain
  • 2010
    • Christian-Albrechts-Universität zu Kiel
      • Institute of Clinical Molecular Biology
      Kiel, Schleswig-Holstein, Germany
  • 2000–2009
    • Instituto de Investigaciones Biomedicas de Barcelona
      Barcino, Catalonia, Spain
  • 2007
    • Instituto Oncológico Baselga
      Barcino, Catalonia, Spain
  • 2006–2007
    • The Centro Español de Investigación Farmacoepidemiológica
      Madrid, Madrid, Spain
  • 2002–2005
    • Hospital Universitari Germans Trias i Pujol
      • Department of Rheumatology
      Badalona, Catalonia, Spain
  • 2003
    • Hospital Clínico Universitario Lozano Blesa, Zaragoza
      Caesaraugusta, Aragon, Spain
  • 2000–2001
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 1998
    • Spanish National Research Council
      Madrid, Madrid, Spain
  • 1994–1998
    • Louisiana State University in Shreveport
      Shreveport, Louisiana, United States
  • 1997
    • LSU Medical Center
      • Department of Physiology
      Shreveport, Louisiana, United States
  • 1988–1991
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain