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909 results on '"Cottone, M"'

1. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

Author

Rahier, J.F., Magro, F., Abreu, C., Armuzzi, A., Ben-Horin, S., Chowers, Y., Cottone, M., de Ridder, L., Doherty, G., Ehehalt, R., Esteve, M., Katsanos, K., Lees, C.W., MacMahon, E., Moreels, T., Reinisch, W., Tilg, H., Tremblay, L., Veereman-Wauters, G., Viget, N., Yazdanpanah, Y., Eliakim, R., and Colombel, J.F.

Published
2014
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3. P412 The Sicilian network of biological therapy in inflammatory bowel disease: preliminary data on efficacy

Author

Orlando, A., Macaluso, F.S., Fries, W., Privitera, A.C., Cappello, M., Siringo, S., Inserra, G., Magnano, A., Di Mitri, R., Belluardo, N., Scarpulla, G., Magrì, G., Trovatello, N., Carroccio, A., Genova, S., Calandruccio, G., Vassallo, R., Romano, C., Pellegrino, S., Citrano, M., Accomando, S., Ventimiglia, M., Renna, S., Orlando, R., Rizzuto, G., Vinci, E., and Cottone, M.

Published
2017
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7. Burden of Crohn’s disease: economics and quality of life aspects in Italy

Author

Benedini V, Caporaso N, Corazza GR, Rossi Z, Fornaciari G, Cottone M, Frosini G, Caruggi M, Ottolini C, and Colombo GL

Subjects
Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Viviano Benedini,1 Nicola Caporaso,2 Gino Roberto Corazza,3 Zaccaria Rossi,4 Giovanni Fornaciari,5 Mario Cottone,6 Giorgio Frosini,7 Mauro Caruggi,8 Chiara Ottolini,8 Giorgio L Colombo9,10 On behalf of the COSMO Study Group1Department of Gastroenterology, AO Carlo Poma, Mantova; 2Department of Gastroenterology, University of Naples, Federico II, Naples; 3IRCCS Policlinico San Matteo, Pavia; 4Department of Gastroenterology, Ospedale Regina Apostolorum, Albano Laziale, Rome; 5Department of Gastroenterology, Arcispedale S Maria Nuova, Reggio Emilia; 6Medical Division, Azienda Ospedaliera Cervello, Palermo; 7Department of Gastroenterology, Policlinico Universitario Senese, Siena; 8Hospital S Antonio Abate, Gallarate, Varese, 9University of Pavia; School of Pharmacy, Pavia, Lombardy; 10Studi Analisi Valutazioni Economiche (SAVE), Milan, ItalyBackground: This was a prospective observational study designed to evaluate direct and indirect costs and quality of life for patients with Crohn’s disease in Italy from the perspectives of the National Health System and of society.Methods: A total of 162 male and female subjects aged 18–70 years with Crohn’s disease in the active phase and a Crohn’s Disease Activity Index score ≥150 were included in the study. Subjects were recruited from 25 Italian centers on a consecutive basis. The study consisted of four visits undertaken every 6 months with a follow-up period of 18 months. The study started on September 1, 2006 and was completed on April 12, 2010. Multivariate analyses were carried out on demographic characteristics, treatment costs based on the prescribed daily dose, resource use and other cost parameters, and changes in quality of life using the EQ5D questionnaire.Results: Cost of illness per subject with Crohn’s disease in Italy was estimated to be €15,521 per year, with direct costs representing 76% of total costs. Nonhealth care costs and loss of productivity accounted for 24% of total costs. Societal costs during the first months of enrolment were higher compared with costs in the final months of the study. Quality of life measured by the EQ-5D was 0.558 initially and then increased to 0.739, with a mean value of 0.677 during the enrolment period. The cost of illness was not correlated with age or gender.Conclusion: The cost of illness was correlated with quality of life; Crohn’s disease had a negative impact on subjects’ quality of life, and higher costs corresponded to a lower quality of life as measured with the EQ5D. Drug treatment may improve quality of life and reduce hospitalization costs. Our results appear to be in line with the results of other international cost-of-illness studies.Keywords: Crohn’s disease, quality of life, EuroQol, EQ5D, cost-of-illness, cost analysis, economic evaluation

Published
2012

8. Infliximab to treat Crohn’s disease: an update

Author

Criscuoli V and Cottone M

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

M Cottone, V CriscuoliBiomedical Department of Internal and Specialist Medicine, Division of Medicine, Villa Sofia-V Cervello Hospital, Palermo University, Palermo, ItalyAbstract: Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract characterized by recurring flares followed by periods of inactive disease and remission. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab (IFX), a chimeric immunoglobulin G1 monoclonal antibody to tumor necrosis factor, has dramatically changed the approach to managing patients with CD and improving their treatment, by achieving treatment goals, such as mucosal healing, and decreasing the need for hospitalizations and surgeries. This review provides an update on existing evidence for the use of IFX in CD, taking into account the safety profile in clinical practice and special situations such as pregnancy. Antitumor necrosis factor therapy has been evaluated as an induction and maintenance therapy in CD in several randomized controlled trials and meta-analyses, showing efficacy in both clinical settings. Early use of biologics may improve patient outcomes in active CD. However, a widespread use of a “top-down” approach in all CD patients cannot be recommended. Clinical factors at diagnosis may predict poor outcome in CD, and should be taken into account when determining the initial therapeutic approach.Keywords: Crohn’s disease, infliximab, adult

Published
2011

12. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Author

Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., S. M. E., Ng, Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., S. M., Ng, Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., Ng, S. M. E., Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., Ng, S. M., Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Daly, Mark J. [0000-0002-0949-8752], Apollo - University of Cambridge Repository, Hugot, Jean-Pierre [0000-0002-8446-6056], UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Romagnoni, A, Jegou, S, VAN STEEN, Kristel, Wainrib, G, Hugot, JP, Peyrin-Biroulet, L, Chamaillard, M, Colombel, JF, Cottone, M, D'Amato, M, D'Inca, R, Halfvarson, J, Henderson, P, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Ng, SME, Oikonomou, I, Peeters, H, Proctor, DD, Rahier, JF, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Andrews, JM, Bampton, PA, Barclay, M, Florin, TH, Gearry, R, Krishnaprasad, K, Lawrance, IC, Mahy, G, Montgomery, GW, Radford-Smith, G, Roberts, RL, Simms, LA, Hanigan, K, Croft, A, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie, AM, Beck, K, Bernard, EJ, Binion, DG, Bitton, A, Brant, SR, Cho, JH, Cohen, A, Croitoru, K, Daly, MJ, Datta, LW, Deslandres, C, Duerr, RH, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, GR, Haritunians, T, Jobin, G, Katz, S, Lahaie, RG, McGovern, DP, Nelson, L, Ng, SM, Ning, K, Pare, P, Regueiro, MD, Rioux, JD, Ruggiero, E, Schumm, LP, Schwartz, M, Scott, R, Sharma, Y, Silverberg, MS, Spears, D, Steinhart, AH, Stempak, JM, Swoger, JM, Tsagarelis, C, Zhang, C, Zhao, HY, AERTS, Jan, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, CM, Coffey, AJ, Mc Connell, J, Conrad, DF, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Frayling, TM, Freathy, RM, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Marchini, JL, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, McVean, G, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Munroe, PB, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Ovington, NR, Owen, MJ, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, JRB, Phillips, A, Plagnol, V, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Sawcer, SJ, Schuilenburg, H, Scott, CE, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stirrups, K, Stone, MA, Strachan, DP, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Tobin, MD, Travers, ME, Turnbull, C, Vukcevic, D, Wain, LV, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Yau, C, Young, AH, Zeggini, E, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Hurles, ME, Duncanson, A, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Kwiatkowski, DP, McCarthy, MI, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Jankowski, J, Markus, HS, Palmer, CNA, Plomin, R, Rautanen, A, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, and Kwiatkowski, D

Subjects
Male, 692/4020/1503/257/1402, Genotype, Genotyping Techniques, LOCI, 45/43, lcsh:Medicine, Polymorphism, Single Nucleotide, Crohn's disease, genetics, genome wide association, Article, Deep Learning, Crohn Disease, INDEL Mutation, Genetics research, Humans, genetics, Genetic Predisposition to Disease, 129, lcsh:Science, Alleles, Science & Technology, genome wide association, RISK PREDICTION, 45, Models, Genetic, lcsh:R, Decision Trees, 692/308/2056, ASSOCIATION, Multidisciplinary Sciences, Crohn's disease, Logistic Models, Nonlinear Dynamics, ROC Curve, Area Under Curve, Science & Technology - Other Topics, lcsh:Q, Female, Neural Networks, Computer, INFLAMMATORY-BOWEL-DISEASE, Genome-Wide Association Study
Abstract

Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise.

Published
2019

18. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author

Patsopoulos, NA, Baranzini, SE, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, AH, James, T, Replogle, J, Vlachos, IS, McCabe, C, Pers, TH, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, IP, Robbins, A, Andlauer, TFM, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, HB, Sellebjerg, F, Sorensen, PS, Ullum, H, Thorner, LW, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, CM, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, MD, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, MA, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, SD, Celius, EG, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, IL, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, SJ, Calabresi, P, Cree, BAC, Cross, A, Davis, M, de Bakker, PWI, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, IY, Gourraud, PA, Haines, JL, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, MH, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, CP, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, MA, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, RJ, Lechner-Scott, J, Leal, R, Moscato, P, Booth, DR, Stewart, GJ, Vucic, S, Pame, G, BamettO, M, Mason, D, GriffithS, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, BV, Charlesworth, J, Kilpatrick, TJ, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, WM, Kermode, AG, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, JF, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, JP, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, GW, Ng, SME, Oikonomnou, J, Peeters, H, Proctor, DD, Rahier, JF, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, DA, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, HF, Hauser, SL, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, LF, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, McCauley, JL, Oksenberg, JR, Oturai, A, Sawcer, S, Ivinson, AJ, Olsson, T, De Jager, PL, Patsopoulos, Na, Baranzini, Se, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, Ah, James, T, Replogle, J, Vlachos, I, Mccabe, C, Pers, Th, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, Ip, Robbins, A, Andlauer, Tfm, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, Hb, Sellebjerg, F, Sorensen, P, Ullum, H, Thorner, Lw, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, Cm, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, Md, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, Ma, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, Sd, Celius, Eg, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, Il, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, Sj, Calabresi, P, Cree, Bac, Cross, A, Davis, M, de Bakker, Pwi, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, Iy, Gourraud, Pa, Haines, Jl, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, Mh, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, Cp, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, Ma, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, Rj, Lechner-Scott, J, Leal, R, Moscato, P, Booth, Dr, Stewart, Gj, Vucic, S, Pame, G, Bametto, M, Mason, D, Griffiths, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, Bv, Charlesworth, J, Kilpatrick, Tj, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, Wm, Kermode, Ag, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, Jf, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, Gw, Ng, Sme, Oikonomnou, J, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, Km, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H, Mathew, Cg, Palmer, Cna, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cca, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, Da, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, Hf, Hauser, Sl, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, Lf, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, Mccauley, Jl, Oksenberg, Jr, Oturai, A, Sawcer, S, Ivinson, Aj, Olsson, T, De Jager, Pl, Neurology, and Immunology

Subjects
0301 basic medicine, Multiple Sclerosis, Quantitative Trait Loci, Inheritance Patterns, Cell Cycle Proteins, Genome-wide association study, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Major Histocompatibility Complex, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Gene Frequency, Autoimmune Process, medicine, Humans, RNA-Seq, X chromosome, Genetics, Chromosomes, Human, X, Multidisciplinary, Microglia, Multiple sclerosis, GTPase-Activating Proteins, Chromosome Mapping, Genomics, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Genetic Loci, Case-Control Studies, biology.protein, Genome-Wide Association Study, 030217 neurology & neurosurgery
Abstract

Genetic roots of multiple sclerosis The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis. Science , this issue p. eaav7188 ; see also p. 1383

Published
2019

19. Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial

Author

Orlando, A, Mocciaro, F, Ventimiglia, M, Renna, S, Rispo, A, Scribano, M, Testa, A, Aratari, A, Bossa, F, Angelucci, E, Onali, S, Cappello, M, Giunta, M, Scimeca, D, Macaluso, F, Castiglione, F, Papi, C, Annese, V, Biancone, L, Kohn, A, Di Mitri, R, and Cottone, M

Subjects
Settore MED/12, Crohn Disease, Double-Blind Method, Recurrence, Azathioprine, Humans, Mesalamine
Abstract

The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER.We performed a 1-year multicenter randomized double-blind double-dummy trial. Primary end-points were endoscopic improvement and therapeutic failure (clinical recurrence or drug discontinuation due to lack of efficacy or adverse events) 12 months after randomization. We also performed a post-trial analysis on symptomatic and endoscopic outcomes 10 years after the beginning of the trial, with a median follow-up of 60 months.Therapeutic failure occurred in 8 patients (17.4%) within 12 months from randomization, with no significant difference between patients treated with 5-ASA (20.8%, 5 patients) and those with AZA (13.6%, 3 patients). Therapeutic failure was due to clinical recurrence in the 5-ASA group and to adverse events in the AZA group. Endoscopic improvement at 12 months was observed in 8 patients, 2 (11.8%) in the 5-ASA group and 6 (30%) in the AZA group. No serious adverse event was recorded. At the post-trial analysis (median follow-up 60 months), 47.8% (22/46) of patients experienced clinical recurrence: 54.2% (13/24) in the 5-ASA group and 40.9% (9/22) in the AZA group, p=0.546. Patients treated with AZA had lower risk of drug escalation. Clinical recurrence was associated with smoking (p=0.031) and previous surgery (p=0.003).Our trial indicates that there was no difference in terms of treatment failure between 5-ASA and AZA in patients with severe ER. The main limit of AZA is its less favorable safety profile.

Published
2020

20. Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study

Author

Biancone, L., Orlando, A., Kohn, A., Colombo, E., Sostegni, R., Angelucci, E., Rizzello, F., Castiglione, F., Benazzato, L., Papi, C., Meucci, G., Riegler, G., Petruzziello, C., Mocciaro, F., Geremia, A., Calabrese, E., Cottone, M., and Pallone, F.

Subjects
Infliximab -- Complications and side effects, Infliximab -- Research, Crohn's disease -- Drug therapy, Gastrointestinal tumors -- Risk factors, Health
Published
2006

24. OC.02.3 A PROPENSITY SCORE WEIGHTED COMPARISON OF VEDOLIZUMAB, ADALIMUMAB, AND GOLIMUMAB IN PATIENTS WITH ULCERATIVE COLITIS: REAL-LIFE DATA FROM THE SICILIAN NETWORK FOR INFLAMMATORY BOWEL DISEASE (SN-IBD)

Author

Macaluso, F.S., primary, Ventimiglia, M., additional, Fries, W., additional, Viola, A., additional, Cappello, M., additional, Scrivo, B., additional, Magnano, A., additional, Pluchino, D., additional, Camilleri, S., additional, Garufi, S., additional, Di Mitri, R., additional, Mocciaro, F., additional, Magrì, G., additional, Ferracane, C., additional, Citrano, M., additional, Graziano, F., additional, Bertolami, C., additional, Renna, S., additional, Orlando, R., additional, Rizzuto, G., additional, Cottone, M., additional, and Orlando, A., additional

Published
2020
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25. PC.01.2 A PROPENSITY SCORE WEIGHTED COMPARISON OF VEDOLIZUMAB AND ADALIMUMAB IN CROHN'S DISEASE: REAL-LIFE DATA FROM THE SICILIAN NETWORK FOR INFLAMMATORY BOWEL DISEASE (SN-IBD)

Author

Macaluso, F.S., primary, Ventimiglia, M., additional, Fries, W., additional, Viola, A., additional, Sitibondo, A., additional, Cappello, M., additional, Scrivo, B., additional, Busacca, A., additional, Privitera, A.C., additional, Camilleri, S., additional, Garufi, S., additional, Di Mitri, R., additional, Mocciaro, F., additional, Belluardo, N., additional, Giangreco, E., additional, Bertolami, C., additional, Renna, S., additional, Orlando, R., additional, Rizzuto, G., additional, Cottone, M., additional, and Orlando, A., additional

Published
2020
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26. P690 A propensity score weighted comparison of vedolizumab, adalimumab, and golimumab in patients with ulcerative colitis: Real-life data from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD)

Author

Macaluso, F S, primary, Ventimiglia, M, additional, Fries, W, additional, Viola, A, additional, Cappello, M, additional, Scrivo, B, additional, Magnano, A, additional, Pluchino, D, additional, Camilleri, S, additional, Garufi, S, additional, Di Mitri, R, additional, Mocciaro, F, additional, Magrì, G, additional, Ferracane, C, additional, Citrano, M, additional, Graziano, F, additional, Bertolami, C, additional, Renna, S, additional, Orlando, R, additional, Rizzuto, G, additional, Cottone, M, additional, and Orlando, A, additional

Published
2020
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27. P325 A propensity score-weighted comparison of vedolizumab and adalimumab in Crohn’s disease: Real-life data from the Sicilian Network for inflammatory bowel disease (SN-IBD)

Author

Macaluso, F S, primary, Ventimiglia, M, additional, Fries, W, additional, Viola, A, additional, Sitibondo, A, additional, Cappello, M, additional, Scrivo, B, additional, Busacca, A, additional, Privitera, A C, additional, Camilleri, S, additional, Garufi, S, additional, Di Mitri, R, additional, Mocciaro, F, additional, Belluardo, N, additional, Giangreco, E, additional, Bertolami, C, additional, Renna, S, additional, Orlando, R, additional, Rizzuto, G, additional, Cottone, M, additional, and Orlando, A, additional

Published
2020
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28. CLINICAL COURSE OF SEVERE COLITIS: A COMPARISON BETWEEN CROHN'S DISEASE AND ULCERATIVE COLITIS

Author

Sinagra,E, Orlando,A, Scalisi,A, Mocciaro F, Criscuoli V, Oliva,L, Maisano,S, Giunta,M, La Seta, F, Solina G, Rizzo AG, Leone,A, Tomasello,G, Cappello,F, Cottone,M, Sinagra,E, Orlando,A, Scalisi,A, Mocciaro,F, Criscuoli,V, Oliva,L, Maisano,S, Giunta,M, La Seta, F, Solina,G, Rizzo,AG, Leone,A, Tomasello,G, Cappello,F, and Cottone,M

Subjects
Adult, Male, Settore MED/18 - Chirurgia Generale, Settore MED/12 - Gastroenterologia, Crohn Disease, Humans, Colitis, Ulcerative, Female, colectomy, Crohn's diesease, ulcerative colitis, Middle Aged
Abstract

Few data are available about the clinical course of severe colonic Crohn’s disease (CD). The aim of this study is to describe the clinical course of severe Crohn’s colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohn’s colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn’s Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohn’s colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohn’s colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohn’s colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease.

Published
2018

29. Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A propensity score-matched comparison of infliximab and adalimumab in naïve and non-naïve patients with Crohn’s disease

Author

Orlando, A., Macaluso, F., Fries, W., Privitera, A., Cappello, M., Siringo, S., Inserra, G., Magnano, A., Di Mitri, R., Belluardo, N., Scarpulla, G., Magrì, G., Trovatello, N., Carroccio, A., Genova, S., Bertolami, C., Vassallo, R., Ventimiglia, M., Renna, S., Orlando, R., Rizzuto, G., Cottone, M., and Orlando A., Macaluso F.S., Fries W., Privitera A.C., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello N., Carroccio A., Genova S., Bertolami C., Vassallo R., Ventimiglia M., Renna S., Orlando R., Rizzuto G, Cottone M.

Subjects
Sicilian Network, Inflammatory Bowel Disease, SN-IBD, Settore MED/09 - Medicina Interna
Abstract

Background: In the absence of head-to-head trials, there is an unmeet need to better understand the relative effectiveness of different biologics in inflammatory bowel disease (IBD). The Sicilian Network for Inflammatory Bowel Disease (SN-IBD) is a group composed by all Sicilian centres which continuously enter in a web-based software all clinical data of IBD patients treated with biologics. Methods: Data of all incident Crohn’s disease (CD) patients treated with infliximab (IFX) and adalimumab (ADA) from January 2013 to April 2017 were extracted from the cohort of SN-IBD. Patients were divided in biologic-naïve and non-naïve, and the two groups were analysed singularly. We used a one-to-two propensity score matching (1 IFX: 2 ADA) accounting for the main baseline characteristics in naïve patients, and a one-to-one propensity score matching (1 IFX: 1 ADA) in non-naïve. Results: Seven hundred and forty-seven naïve and 188 non-naïve patients were included. After propensity score matching, 453 naïve (IFX: 151; ADA: 302) and 100 non-naïve patients (total treatments: 122; IFX: 61; ADA: 61) were analysed. Among naïve patients, the rates of response/remission at 12 weeks for IFX and ADA were 80.1% and 81.1%,, respectively (adjusted OR 0.97, p = 0.923); over a median follow-up of 11.8 months, the rates of response/remission for IFX and ADA were 70.2% and 66.2%, respectively, without significant differences (adjusted OR 1.14, p = 0.401). Among non-naïve patients, the rates of response/remission at 12 weeks for IFX and ADA were 68.9% and 60.7%, respectively (adjusted OR 1.54, p = 0.320); over a median follow-up of 8.9 months, the rates of response/remission for IFX and ADA were 57.4% and 54.1%, respectively, without significant differences (adjusted OR 1.96, p = 0.297). Cox regression analysis showed no differences in risk of treatment failure between ADA and IFX, neither in naïve (adjusted HR 1.23, p = 0.381) nor in non-naïve patients (adjusted HR 1.23, p = 0.488). At multivariable conditional logistic regression analysis of naïve CD patients, upper GI involvement (OR 0.18, p = 0.038), previous surgery (OR 0.24, p = 0.003), and older age (OR 0.97, p = 0.036) were associated with lower clinical benefit at 12 weeks, while previous surgery was the only independent predictor of treatment failure at the end of follow-up (HR 2.13, p = 0.03). Mixed effect Cox analysis showed that non-naïve patients experiencing more than one previous line of treatment with biologics have a significant higher risk of treatment failure compared with those previously treated with one biologic only (HR 2.57, p = 0.002) Conclusions: In this large, propensity score matched, real-life, multicentre, cohort study of CD patients, there was no significant difference in the effectiveness of ADA and IFX. Both drugs showed a good efficacy.

Published
2018

35. Clinical and endoscopic presentation of primary gastric lymphoma: a multicentre study

Author

ANDRIANI, A., ZULLO, A., DI RAIMONDO, F., PATTI, C., TEDESCHI, L., RECINE, U., CARUSO, L., BONANNO, G., CHIARENZA, A., LIZZANI, G., MIEDICO, A., ROMANELLI, A., COSTA, A., LINEA, C., MARRONE, C., MIRTO, S., MISTRETTA, A., MONTALBANO, L., RESTIVO, G., VINCI, M., BIBAS, M., HASSAN, C., STELLA, F., COTTONE, M., and MORINI, S.

Published
2006

43. The Sicilian network of biological therapy in inflammatory bowel disease: preliminary data on efficacy

Author

Orlando A., Macaluso F. S., Fries W., Privitera A. C., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello N., Carroccio A., Genova S., Calandruccio G., Vassallo R., Romano C., Pellegrino S., Citrano M., Accomando S., Ventimiglia M., Renna S., Orlando R., Rizzuto G., Vinci E., Cottone M., and Orlando A., Macaluso F.S., Fries W., Privitera A.C., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello N., Carroccio A., Genova S., Calandruccio G., Vassallo R., Romano C., Pellegrino S., Citrano M., Accomando S., Ventimiglia M., Renna S., Orlando R., Rizzuto G., Vinci E., Cottone M.

Subjects
Settore MED/09 - Medicina Interna, biological therapy, inflammatory bowel disease, Sicilian network
Abstract

Background: The monitoring of appropriateness, costs, and clinical outcomes of biological therapy in inflammatory bowel disease (IBD) is a relevant need. We aimed to evaluate all these issues in Sicily through a web based network of all prescribing centers. Methods: From January 2013, all IBD patients starting a biological agent (incident cases) or already on treatment (prevalent cases) were entered in a web based software. Herein we report data of incident cases about the efficacy of biological therapy after twelve weeks and one year of treatment. Results: From January 2013 to October 2016, 1475 patients were included. Incident cases were 1090. Considering that 16% of patients experienced more than one line of therapy, a total of 1351 treatments were reported. Adalimumab was used in 622 Crohn’s disease (CD) patients and in 83 ulcerative colitis (UC)/unclassified colitis patients. Infliximab was prescribed in 275 CD patients (80 biosimilars) and in 279 UC patients (50 biosimilars). Golimumab was used in 32 UC patients, while vedolizumab in 40 CD patients and in 20 UC patients. In patients with CD, after twelve weeks and one year of therapy, the rates of remission with adalimumab were 43.9% and 60.2%, respectively, and the rates of response 40.9% and 25.8%, while the rates of remission with infliximab originator were 46.2% and 50.0%, and the rates of response 40.9% and 32.9% (biosimilars: remission 31.0% and response 51.7% after 12 weeks; remission 45.5% and response 36.4% after one year). In UC, after twelve weeks and one year of therapy, the rates of remission with adalimumab were 43.3% and 57.1%, respectively, and the rates of response 36.7% and 19.0%; the rates of remission with infliximab originator were 41.6% and 48.4%, and the rates of response 35.6% and 32.3% (biosimilars: remission 30.0% and response 63.3% after 12 weeks; remission 20.0% and response 40.0% after one year); the rate of remission after 12 weeks of therapy with Golimumab was 22.2%, and the rate of response was 33.3%. After twelve weeks of therapy with Vedolizumab, 28.6% of CD patients were in remission and 32.0% had a response, while the rates of remission and response in UC patients were 33.3% and 22.0%, respectively. Multivariable logistic regression analysis showed that age >50 years was independently linked to lower rates of remission/response at 12 weeks in CD patients (OR 0.613, p=0.046). Conclusions: In one of the largest series of IBD patients on biological therapy reported to date, CD patients older than 50 years showed a higher rate of non response at 12 weeks of treatment. Efficacy of biosimilars was overall comparable to that reported for infliximab originator.

Published
2017

44. The sicilian network of biological therapy in inflammatory bowel disease: preliminary data from a prospective study on efficacy and safety

Author

Orlando A., Fries W., Privitera A., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello A., Carroccio A., Genova S., Calandruccio G., Vassallo R., Romano C, Magazzù G., Citrano M., Accomando S., Ventimiglia M., Renna S., Orlando R., Rizzuto G., Vinci E., Macaluso F. S., Cottone M., and Orlando A., Fries W., Privitera A., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello A., Carroccio A., Genova S., Calandruccio G., Vassallo R., Romano C, Magazzù G., Citrano M., Accomando S., Ventimiglia M., Renna S., Orlando R., Rizzuto G., Vinci E., Macaluso F.S., Cottone M.

Subjects
Settore MED/09 - Medicina Interna, biological therapy, inflammatory bowel disease, Sicilian network
Abstract

Background and aim: The monitoring of appropriateness and costs of biological therapy in Inflammatory bowel disease (IBD) is a relevant need. We aimed to evaluate appropriateness, efficacy and safety of biological therapy in IBD in Sicily through a web based network of prescribing centers. Material and methods: The Sicilian network for the monitoring of biological therapy in IBD is composed by a super Hub coordinator center and five Hub plus ten Spoke centers. From January 2013 all IBD patients starting a biological agent (incident cases) or already on treatment (prevalent cases) were entered in a web based software. Herein we report data on remission and response after twelve weeks of biological therapy, and side effects until the end of follow-up of incident cases. Results: From January 2013 to June 2016, 1475 patients were included. Complete data were available in 1338 cases (983 with Crohn’s disease [CD], 345 with ulcerative colitis [UC], and 10 with unclassified colitis). Incident cases were 956 (673 CD, 274 UC, and 9 unclassified colitis). Considering that 12% of patients experienced more than one line of therapy, a total of 1098 treatments were reported. Adalimumab was used in 543 CD patients, in 69 UC patients, and in 4 with unclassified colitis. Infliximab was prescribed in 221 CD patients (64 biosimilars), in 226 UC patients (41 biosimilars), and in 5 patients with unclassified colitis. Golimumab was prebscribed in 29 UC patients, and in 1 patient with unclassified colitis. After twelve weeks, the rate of response with Adalimumab was 46% and the rate of remission was 38% in CD, while the rate of response with Infliximab originator was 48% and the rate of remission 42% (biosimilars: 37% and 50%, respectively). In UC the rate of response with Adalimumab was 46% and the rate of remission was 38%, the rate of response with Infliximab was 41% and the rate of remission 45% (biosimilars: 25% and 64%, respectively), while the rate of response with Golimumab was 47% and the rate of remission was 27%. Overall, the rate of side effects was 17% (9.2% with Adalimumab, 20% with Infliximab originator, 15% with biosimilars, and 17% with Golimumab). Conclusions: In one of the largest series of IBD patients on biological therapy reported to date, the rates of remission and response after twelve weeks were comparable to data from literature, and similar between the different biologics. Efficacy and safety of biosimilars were analogous to those reported for infliximab originator.

Published
2017

45. A real life comparison of the efficacy of adalimumab versus golimumab in moderate-to-severe ulcerative colitis. A multicenter experience from the sicilian network for inflammatory bowel disease (SN-IBD)

Author

Renna, S., Mocciaro, F., Ventimiglia, M., Macaluso, F., Orlando, R., Billeci, M., Cappello, M., Mendolaro, M., Privitera, A., Ferracane, C., Fries, W., Pisana, V., Magnano, A., Pluchino, D., Inserra, G., Scarpulla, G., Garufi, S., Carroccio, A., Siringo, S., Dimitri, R., Cottone, M., Orlando, A., and Renna S., Mocciaro F., Ventimiglia M., Macaluso F.S., Orlando R., Billeci M., Cappello M., Mendolaro M., Privitera A.C., Ferracane C., Fries W., Pisana V., Magnano A., Pluchino D., Inserra G., Scarpulla G., Garufi S., Carroccio A., Siringo S., Dimitri R., Cottone M., Orlando A.

Subjects
adalimumab, golimumab, ulcerative colitis, sicilian network, inflammatory bowel disease, SN-IBD, Settore MED/09 - Medicina Interna, ulcerative coliti
Abstract

Introduction: Adalimumab (ADA) and golimumab (GOL) are effective in the induction and maintenance treatment of moderate-to-severe ulcerative colitis (UC). No comparable data between the 2 drugs are available up to now. Aims & Methods: We reported the Sicilian Network experience on the comparative efficacy of ADA and GOL in patients (pts) with moderate-to-severe UC. From June 2015 until April 2017, 197 consecutive pts with moderate to severe UC were treated with ADA or GOL. The efficacy was evaluated at 8 week and at the end of the follow up considering ‘‘clinical response’’ (reduction of at least 2 points of Partial Mayo Score with concomitant steroid reduction or discontinuation) and “clinical remission” (Partial Mayo Score 52 without steroids). The presence of clinical response or clinical remission was defined as “clinical benefit”. Endoscopic Mayo Score was evaluated at the end of the follow up in pts who underwent colonoscopy. Results: 118 pts were treated with ADA and 79 with GOL for a median follow up of 40.21 [20.32, 69.14] weeks for ADA and 34.00 [17.43, 54.79] weeks for GOL (p ¼ 0.08). Eighty-eight pts were naive to anti-TNF (59 ADA, 29 GOL, p = 0.09). No difference in Mayo Score value was observed between the 2 groups at the time of first drug injection (p = 0.92). After 8 weeks clinical benefit was achieved in 93/118 (78.8%) pts treated with ADA and 50/79 (63.3%) pts treated with GOL (p = 0.026). Clinical remission was achieved in 48/118 (40.7%) pts treated with ADA and 20/79 (25.3%) pts treated with GOL (p = 0.038). At the end of the follow up clinical benefit was achieved in 79/118 (66.9%) pts treated with ADA and 37/79 (46.8%) pts treated with GOL (p = 0.008). Clinical remission was achieved in 50/118 (42.4%) pts treated with ADA and 23/79 (29.1%) pts treated with GOL (p = 0.082). No difference was observed in clinical outcomes at 8 weeks and at the end of the follow up between naive and non naive pts (p = 0.187). At the end of the follow up the median Endoscopic Mayo Score was 3.00 [0.00, 5.00] in pts treated with ADA and 4.00 [1.00, 7.00] in pts treated with GOL (p = 0.025). Univariable analysis revealed that age4 40 years at the time of first drug injection and age5 40 years at the diagnosis were associated with higher remission rate in pts treated with ADA respect to pts treated with GOL at 8 weeks and at the end of the follow up (p = 0.034 and p = 0.016 respectively). Disease duration 45 years was associated with a higher remission rate in pts treated with ADA respect to pts treated with GOL at 8 weeks and at the end of the follow up (p = 0.017). Conclusion: This is the first study where the comparable efficacy of ADA and GOL was evaluated. These real life data confirmed the efficacy of subcutaneous anti-TNF in the treatment of moderate to severe UC. ADA resulted to be more effective than GOL in inducing and maintaining clinical benefit. Larger prospective studies with longer follow up are warranted to confirm this data

Published
2017

46. The sicilian network for inflammatory bowel disease (SN-IBD): preliminary data on efficacy of biological therapy

Author

Orlando, A., Macaluso, F., Fries, W., Privitera, A., Cappello, M., Siringo, S., Inserra, G., Magnano, A., Di Mitri, R., Belluardo, N., Scarpulla, G., Magrì, G., Trovatello, A., Carroccio, A., Genova, S., Bertolami, C., Vassallo, R., Romano, C., Pellegrino, S., Citrano, M., Accomando, S., Ventimiglia, M., Renna, S., Orlando, R., Rizzuto, G., Vinci, E., Cottone, M., and Orlando A., Macaluso F.S., Fries W., Privitera A.C., Cappello M., Siringo S., Inserra G., Magnano A., Di Mitri R., Belluardo N., Scarpulla G., Magrì G., Trovatello A., Carroccio A., Genova S., Bertolami C., Vassallo R., Romano C., Pellegrino S., Citrano M., Accomando S., Ventimiglia M., Renna S., Orlando R., Rizzuto G., Vinci E., Cottone M.

Subjects
Settore MED/09 - Medicina Interna, Sicilian network, inflammatory bowel disease, SN-IBD
Abstract

Introduction: The monitoring of appropriateness, costs, and clinical outcomes of biological therapy in inflammatory bowel disease (IBD) is a relevant need. Aims & Methods: We aimed to evaluate all these issues in Sicily through a webbased network of all prescribing centers. The Sicilian Network for Inflammatory Bowel Disease (SN-IBD) is composed by a super Hub coordinator centre and five Hub plus ten Spoke centres. From January 2013, all IBD patients starting a biological agent (incident cases) or already on treatment (prevalent cases) were entered in a web based software. Herein we report data of incident cases about the efficacy of biological therapy after twelve weeks and one year of treatment. As clinical end-point, we set remission (corresponding to a Mayo Partial Score 52 for UC, and to a Harvey-Bradshaw Index 55 for CD), and response (reduction of Harvey-Bradshaw Index

Published
2017

49. P.07.1 ELDERLY PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD) ARE LESS LIKELY TO PERSIST ON ANTI-TNF THERAPY COMPARED WITH YOUNGER PATIENTS. DATA FROM THE SICILIAN NETWORK FOR INFLAMMATORY BOWEL DISEASES (SN-IBD)

Author

Porcari, S., primary, Fidanza, O., additional, Alibrandi, A., additional, Renna, S., additional, Cappello, M., additional, Siringo, S., additional, Privitera, A.C., additional, Inserra, G., additional, Mocciaro, F., additional, Magrì, G., additional, Carroccio, A., additional, Belluardo, N., additional, Bertolami, C., additional, Garufi, S., additional, Ventimiglia, M., additional, Macaluso, F.S., additional, Viola, A., additional, Cottone, M., additional, Orlando, A., additional, and Fries, W., additional

Published
2019
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