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IRIS
BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy.
Ustekinumab as induction and maintenance therapy for Crohn's disease / Feagan, B. G.; Sandborn, W. J.; Gasink, C.; Jacobstein, D.; Lang, Y.; Friedman, J. R.; Blank, M. A.; Johanns, J.; Gao, L. -L.; Miao, Y.; Adedokun, O. J.; Sands, B. E.; Hanauer, S. B.; Vermeire, S.; Targan, S.; Ghosh, S.; De Villiers, W. J.; Colombel, J. -F.; Tulassay, Z.; Seidler, U.; Salzberg, B. A.; Desreumaux, P.; Lee, S. D.; Loftus, E. V.; Dieleman, L. A.; Katz, S.; Rutgeerts, P.; Bampton, P.; Chung, A.; Connor, S.; Debinski, H.; Leong, R.; Macrae, F.; Pavli, P.; Sorrentino, D.; van den Bogaerde, J.; Vogel, W.; Vogelsang, H.; Louis, E.; Mana, F.; Zaltman, C.; Aumais, G.; Bernstein, C.; Bressler, B.; Dhalla, S.; Marshall, J.; Panaccione, R.; Ropeleski, M.; Stehlik, J.; Volfova, M.; Brynskov, J.; Glerup, H.; Abitbol-Selinger, V.; Allez, M.; Beaugerie, L.; Bourreille, A.; Cadiot, G.; Dupas, J.; Grimaud, J.; Laharie, D.; Lerebours, E.; Moreau, J.; Baumgart, D.; Brand, S.; Ebert, M.; Ehehalt, R.; Hasselblatt, P.; Howaldt, S.; Klaus, J.; Krummenerl, P.; Kucharzik, T.; Lugering, A.; Mudter, J.; Preiss, J.; Schreiber, S.; Stallmach, A.; Stein, J.; Strauch, U.; Salamon, A.; Patchett, S.; Lahat-Zok, A.; Rachmilewitz, D.; Annese, V.; Bossa, F.; Guidi, L.; Kohn, A.; Rocca, R.; Ando, A.; Ashida, T.; Hanai, H.; Ishida, T.; Ito, H.; Matsumoto, T.; Motoya, S.; Nakamura, S.; Sameshima, Y.; Suzuki, Y.; Watanabe, K.; Yamagami, H.; Yamamoto, T.; Yao, K.; Kim, H.; Kim, Y.; D'Haens, G.; Pierik, M.; van Bodegraven, A.; van der Woude, C. J.; Gearry, R.; Ciecko-Michalska, I.; Malecka-Panas, E.; Jojic, N.; Aboo, N.; Wright, J.; Arranz, M.; Viso, L.; Ahmad, T.; Bloom, S.; Campbell, S.; Creed, T.; Cummings, F.; Hawthorne, B.; Iqbal, T.; Ireland, A.; Parkes, M.; Pollok, R.; Shaw, I.; Shonde, A.; Smith, M.; Steel, A.; Subramanian, S.; Travis, S.; Tremelling, M.; Aberra, F.; Abraham, B.; Barish, C.; Behm, B.; Birbara, C.; Bochner, R.; Bologna, S.; Brant, S.; Charles, R.; Cohen, N.; de Villers, W.; Dryden, G.; Duvall, A.; Flasar, M.; Fleisher, M.; Florez, D.; Fogel, R.; Gagneja, H.; Gross, C.; Hamilton, J.; Hanson, J.; Hardi, R.; Higgins, P.; Isaacs, K.; Katz, J.; Kaur, N.; Khan, N.; Leman, B.; Levenson, S.; Lichtiger, S.; Malik, P.; Mcnair, A.; Melmed, G.; Miner, P.; Nichols, M.; Noar, M.; Oikonomou, I.; Oubre, B.; Peterson, K.; Pruitt, R.; Quirk, D.; Safdi, A.; Safdi, M.; Saubermann, L.; Scherl, E.; Schwartz, D.; Schwarz, R.; Sedghi, S.; Selby, L.; Shafran, I.; Siegel, C.; Sninsky, C.; Stern, M.; Stockwell, D.; Stone, C.; Swaminath, A.; Swoger, J.; Taormina, M.; Williams, E.; Winstead, N.; Wolf, D.; Wolosin, J.; Yacyshyn, B.; Yajnik, V.; Yen, E.; Hetzel, D.; Muls, V.; Bafutto, M.; Francesconi, C.; Sipahi, A.; Steinwurz, F.; Churchev, J.; Kotzev, I.; Marinova, I.; Penchev, P.; Spassova, Z.; Stoinov, S.; Takov, D.; Vassileva, G.; Fowler, S.; Greenberg, G.; Jones, J.; Saibil, F.; Salh, B.; Banic, M.; Duvnjak, M.; Stimac, D.; Goujon, G.; Pelletier, A.; Peyrin-Biroulet, L.; Aldinger, V.; Bokemeyer, B.; Buning, C.; Konturek, J.; Krummenerl, T.; Ochsenkuehn, T.; Altorjay, I.; Kis, J.; Pecsi, G.; Szekely, A.; Varga, M.; Vincze, A.; Wacha, J.; Oddsson, E.; Orvar, K.; Avni-Biron, I.; Fishman, S.; Fraser, G.; Konikoff, F.; Melzer, E.; Oren, R.; Shirin, H.; Danese, S.; Marino, M.; Sturniolo, G. C.; Horiki, N.; Iijima, H.; Iwabuchi, M.; Kanai, T.; Kunisaki, R.; Maemoto, A.; Matsuoka, K.; Osada, T.; Sugimoto, K.; Tanaka, S.; Cheon, J. H.; Han, D. S.; Jang, B. I.; Kim, J. S.; Park, S. J.; Yang, S. K.; Arnold, M.; Claydon, A.; Haines, M.; Hill, J.; Rowbotham, D.; Schultz, M.; Wallace, I.; Bochenek, A.; Niezgoda, K.; Szura, M.; Arutyunov, G.; Baranovsky, A.; Khalif, I.; Osipenko, M.; Milinic, N.; Bloch, H.; Kruger, F. C.; Prins, M.; Watermeyer, G.; Ziady, C.; Calvo, Xc.; Dominguez-Munoz, J. E.; Gisbert, J. P.; Arsenescu, R.; Beaulieu, D.; Bedford, R.; Behrend, C.; Cleavinger, P.; Cohen, J.; Ertan, A.; Freilich, B.; Friedenberg, K.; Glover, S.; Gordon, G.; Gunaratnam, N.; Gupta, N.; Holbrook, R.; Jones, M.; Kaufman, B.; Khurana, S.; Legnani, P.; Mutlu, E.; Phillips, R.; Rai, R.; Reichelderfer, M.; Ritter, T.; Safdi, M. A.; Schulman, M.; Smith, J.; Suiter, D.; Taylor, D.; Vasudeva, R.; Winstead, T.; Zwick, A.; Savoye, G.; Atreya, R.; Ochsenkuhn, T.; Ott, C.; Goldin, E.; Shirin, H.; Motohiro, E.; Takanori, K.; James, B.; Cummings, J.; Tariq, A.; Willert, R.; Allan, M.; Bulat, R.; Devilliers, W.; Eaker, E.; Hou, J.; Mendu, S.; Nicols, M.; Proctor, D.; Thosani, N.; Zhang, C.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 375:20(2016), pp. 1946-1960. [10.1056/NEJMoa1602773]
Ustekinumab as induction and maintenance therapy for Crohn's disease
BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy.
Ustekinumab as induction and maintenance therapy for Crohn's disease / Feagan, B. G.; Sandborn, W. J.; Gasink, C.; Jacobstein, D.; Lang, Y.; Friedman, J. R.; Blank, M. A.; Johanns, J.; Gao, L. -L.; Miao, Y.; Adedokun, O. J.; Sands, B. E.; Hanauer, S. B.; Vermeire, S.; Targan, S.; Ghosh, S.; De Villiers, W. J.; Colombel, J. -F.; Tulassay, Z.; Seidler, U.; Salzberg, B. A.; Desreumaux, P.; Lee, S. D.; Loftus, E. V.; Dieleman, L. A.; Katz, S.; Rutgeerts, P.; Bampton, P.; Chung, A.; Connor, S.; Debinski, H.; Leong, R.; Macrae, F.; Pavli, P.; Sorrentino, D.; van den Bogaerde, J.; Vogel, W.; Vogelsang, H.; Louis, E.; Mana, F.; Zaltman, C.; Aumais, G.; Bernstein, C.; Bressler, B.; Dhalla, S.; Marshall, J.; Panaccione, R.; Ropeleski, M.; Stehlik, J.; Volfova, M.; Brynskov, J.; Glerup, H.; Abitbol-Selinger, V.; Allez, M.; Beaugerie, L.; Bourreille, A.; Cadiot, G.; Dupas, J.; Grimaud, J.; Laharie, D.; Lerebours, E.; Moreau, J.; Baumgart, D.; Brand, S.; Ebert, M.; Ehehalt, R.; Hasselblatt, P.; Howaldt, S.; Klaus, J.; Krummenerl, P.; Kucharzik, T.; Lugering, A.; Mudter, J.; Preiss, J.; Schreiber, S.; Stallmach, A.; Stein, J.; Strauch, U.; Salamon, A.; Patchett, S.; Lahat-Zok, A.; Rachmilewitz, D.; Annese, V.; Bossa, F.; Guidi, L.; Kohn, A.; Rocca, R.; Ando, A.; Ashida, T.; Hanai, H.; Ishida, T.; Ito, H.; Matsumoto, T.; Motoya, S.; Nakamura, S.; Sameshima, Y.; Suzuki, Y.; Watanabe, K.; Yamagami, H.; Yamamoto, T.; Yao, K.; Kim, H.; Kim, Y.; D'Haens, G.; Pierik, M.; van Bodegraven, A.; van der Woude, C. J.; Gearry, R.; Ciecko-Michalska, I.; Malecka-Panas, E.; Jojic, N.; Aboo, N.; Wright, J.; Arranz, M.; Viso, L.; Ahmad, T.; Bloom, S.; Campbell, S.; Creed, T.; Cummings, F.; Hawthorne, B.; Iqbal, T.; Ireland, A.; Parkes, M.; Pollok, R.; Shaw, I.; Shonde, A.; Smith, M.; Steel, A.; Subramanian, S.; Travis, S.; Tremelling, M.; Aberra, F.; Abraham, B.; Barish, C.; Behm, B.; Birbara, C.; Bochner, R.; Bologna, S.; Brant, S.; Charles, R.; Cohen, N.; de Villers, W.; Dryden, G.; Duvall, A.; Flasar, M.; Fleisher, M.; Florez, D.; Fogel, R.; Gagneja, H.; Gross, C.; Hamilton, J.; Hanson, J.; Hardi, R.; Higgins, P.; Isaacs, K.; Katz, J.; Kaur, N.; Khan, N.; Leman, B.; Levenson, S.; Lichtiger, S.; Malik, P.; Mcnair, A.; Melmed, G.; Miner, P.; Nichols, M.; Noar, M.; Oikonomou, I.; Oubre, B.; Peterson, K.; Pruitt, R.; Quirk, D.; Safdi, A.; Safdi, M.; Saubermann, L.; Scherl, E.; Schwartz, D.; Schwarz, R.; Sedghi, S.; Selby, L.; Shafran, I.; Siegel, C.; Sninsky, C.; Stern, M.; Stockwell, D.; Stone, C.; Swaminath, A.; Swoger, J.; Taormina, M.; Williams, E.; Winstead, N.; Wolf, D.; Wolosin, J.; Yacyshyn, B.; Yajnik, V.; Yen, E.; Hetzel, D.; Muls, V.; Bafutto, M.; Francesconi, C.; Sipahi, A.; Steinwurz, F.; Churchev, J.; Kotzev, I.; Marinova, I.; Penchev, P.; Spassova, Z.; Stoinov, S.; Takov, D.; Vassileva, G.; Fowler, S.; Greenberg, G.; Jones, J.; Saibil, F.; Salh, B.; Banic, M.; Duvnjak, M.; Stimac, D.; Goujon, G.; Pelletier, A.; Peyrin-Biroulet, L.; Aldinger, V.; Bokemeyer, B.; Buning, C.; Konturek, J.; Krummenerl, T.; Ochsenkuehn, T.; Altorjay, I.; Kis, J.; Pecsi, G.; Szekely, A.; Varga, M.; Vincze, A.; Wacha, J.; Oddsson, E.; Orvar, K.; Avni-Biron, I.; Fishman, S.; Fraser, G.; Konikoff, F.; Melzer, E.; Oren, R.; Shirin, H.; Danese, S.; Marino, M.; Sturniolo, G. C.; Horiki, N.; Iijima, H.; Iwabuchi, M.; Kanai, T.; Kunisaki, R.; Maemoto, A.; Matsuoka, K.; Osada, T.; Sugimoto, K.; Tanaka, S.; Cheon, J. H.; Han, D. S.; Jang, B. I.; Kim, J. S.; Park, S. J.; Yang, S. K.; Arnold, M.; Claydon, A.; Haines, M.; Hill, J.; Rowbotham, D.; Schultz, M.; Wallace, I.; Bochenek, A.; Niezgoda, K.; Szura, M.; Arutyunov, G.; Baranovsky, A.; Khalif, I.; Osipenko, M.; Milinic, N.; Bloch, H.; Kruger, F. C.; Prins, M.; Watermeyer, G.; Ziady, C.; Calvo, Xc.; Dominguez-Munoz, J. E.; Gisbert, J. P.; Arsenescu, R.; Beaulieu, D.; Bedford, R.; Behrend, C.; Cleavinger, P.; Cohen, J.; Ertan, A.; Freilich, B.; Friedenberg, K.; Glover, S.; Gordon, G.; Gunaratnam, N.; Gupta, N.; Holbrook, R.; Jones, M.; Kaufman, B.; Khurana, S.; Legnani, P.; Mutlu, E.; Phillips, R.; Rai, R.; Reichelderfer, M.; Ritter, T.; Safdi, M. A.; Schulman, M.; Smith, J.; Suiter, D.; Taylor, D.; Vasudeva, R.; Winstead, T.; Zwick, A.; Savoye, G.; Atreya, R.; Ochsenkuhn, T.; Ott, C.; Goldin, E.; Shirin, H.; Motohiro, E.; Takanori, K.; James, B.; Cummings, J.; Tariq, A.; Willert, R.; Allan, M.; Bulat, R.; Devilliers, W.; Eaker, E.; Hou, J.; Mendu, S.; Nicols, M.; Proctor, D.; Thosani, N.; Zhang, C.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 375:20(2016), pp. 1946-1960. [10.1056/NEJMoa1602773]
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Feagan, B. G.; Sandborn, W. J.; Gasink, C.; Jacobstein, D.; Lang, Y.; Friedman, J. R.; Blank, M. A.; Johanns, J.; Gao, L. -L.; Miao, Y.; Adedokun, O. ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/166127
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
