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126 results on '"Scherl, E"'

2. P704 Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: The SAPPHIRE Registry

Author

Axelrad, J, primary, Jiang, Y, additional, Colombel, J F, additional, Scherl, E, additional, Lukin, D, additional, Chang, S, additional, Chen, L, additional, Katz, S, additional, Kwah, J, additional, Swaminath, A, additional, Sultan, K, additional, Villagra, C, additional, Jandorf, L, additional, and Itzkowitz, S, additional

Published
2024
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3. DOP35 Spatial transcriptomics reveals cellular niches associated with histological inflammation in postoperative Crohn’s Disease

Author

Battat, R, primary, Sangiorgi, B, additional, Linggi, B, additional, Gui, S, additional, Torti, D, additional, Smith, M I, additional, Mehandru, S, additional, Longman, R, additional, Lukin, D J, additional, Scherl, E J, additional, Qin, L, additional, Ma, C, additional, Teft, W, additional, and Vande Casteele, N, additional

Published
2024
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4. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn’s Disease After Ileocolonic Resection

Author

Debinski, H., Florin, T., Hetzel, D., Lawrance, I., Radford-Smith, G., Sloss, A., Sorrentino, D., Gassner, S., Haas, T., Reicht, G., Reinisch, W., Strasser, M., Vogelsang, H., Bossuyt, P., DeWit, O., D'Haens, G., Franchimont, D., Louis, E., Vermeire, S., Bernstein, C.N., Bourdages, R., Chiba, N., Dhalla, S.S., Feagan, B.G., Fedorak, R.N., Lachance, J.R., Panaccione, R., Ropeleski, M., Singh Salh, B., Lukas, M, Colombel, J-F, Allez, M., Desreumaux, P., Dupas, J.L., Grimaud, J-C., Hebuterne, X., Laharie, D., Lerebours, E., Peyrin-Biroulet, L., Reimund, J-M., Viennot, S., Zerbib, F., Antoni, C., Atreya, R., Baumgart, D.C., Berg, C., Boecker, U., Bramkamp, G., Bünning, C., Ehehalt, R., Howaldt, S., Kucharzik, T., Lamprecht, H.G., Mudter, J., Preiss, J.C., Schreiber, S., Seidler, U., Altorjay, I., Banai, J., Lakatos, P.L., Varga, M., Vincze, A., Avni-Biron, I., Fishman, S., Fraser, G.M., Goldin, E., Rachmilewitz, D., Annese, V., Ardizzone, S., Biancone, L., Bossa, F., Danese, S., Fries, W., Gionchetti, P., Maconi, G., Terrosu, G., Usai, P., D'Haens, G.R., Gearry, R.B., Hill, J., Rowbotham, D.S., Schultz, M., Stubbs, R.S., Wallace, D., Walmsley, R.S., Wyeth, J., Malecka-Panas, E., Paradowski, L., Regula, J., Beales, I.P., Campbell, S., Hawthorne, A.B., Parkes, M., Travis, S.P., Achkar, J.P., Behm, B.W., Bickston, S.J., Brown, K.J., Chiorean, M.V., DeVilliers, W.J.S., Elliott, D.E., Grunkmeier, D., Hamilton, J.W., Hanauer, S.B., Hanson, J.S., Hardi, R., Helper, D.J., Herfarth, H., Higgins, P.D.R., Holderman, W.H., Kottoor, R., Kreines, M.D., Leman, B.I., Li, X., Loftus, E.V., Jr., Noar, M., Oikonomou, I., Onken, J., Peterson, K.A., Phillips, R.P., Randall, C.W., Ricci, M., Ritter, T., Rubin, D.T., Safdi, M., Sandborn, W.J., Sauberman, L., Scherl, E., Schwarz, R.P., Sedghi, S., Shafran, I., Sninsky, C.A., Stein, I., Swoger, J., Vecchio, J., Weinberg, D.I., Wruble, L.D., Yajnik, V., Younes, Z., Regueiro, Miguel, Feagan, Brian G., Zou, Bin, Johanns, Jewel, Blank, Marion A., Chevrier, Marc, Plevy, Scott, Popp, John, Cornillie, Freddy J., Lukas, Milan, Danese, Silvio, Gionchetti, Paolo, Hanauer, Stephen B., Reinisch, Walter, Sandborn, William J., Sorrentino, Dario, and Rutgeerts, Paul

Published
2016
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7. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Author

Sands, B.E., Irving, P.M., Hoops, T., Izanec, J.L., Gao, L.L., Gasink, C., Greenspan, A., Allez, M., Danese, S., Hanauer, S.B., Jairath, V., Kuehbacher, T., Lewis, J.D., Loftus, E.V., Jr., Mihaly, E., Panaccione, R., Scherl, E., Hoentjen, F., Shchukina, O.B., Sandborn, W.J., Sands, B.E., Irving, P.M., Hoops, T., Izanec, J.L., Gao, L.L., Gasink, C., Greenspan, A., Allez, M., Danese, S., Hanauer, S.B., Jairath, V., Kuehbacher, T., Lewis, J.D., Loftus, E.V., Jr., Mihaly, E., Panaccione, R., Scherl, E., Hoentjen, F., Shchukina, O.B., and Sandborn, W.J.

Abstract

Item does not contain fulltext, BACKGROUND: Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. METHODS: We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220-450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. FINDINGS: Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in th

Published
2022

8. P377 Impact of moderate-to-severe endoscopic disease criteria on endoscopic response, endoscopic remission, and deep remission in patients receiving ustekinumab or adalimumab in the SEAVUE study

Author

Allez, M, primary, Lewis, J D, additional, Hanauer, S B, additional, Danese, S, additional, Irving, P M, additional, Gasink, C, additional, Hoops, T, additional, Izanec, J L, additional, Ma, T, additional, Loftus, E V, additional, Scherl, E J, additional, Panaccione, R, additional, Sandborn, W J, additional, and Sands, B E, additional

Published
2022
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9. Joint Disease Activity in IBD-associated Peripheral Spondyloarthritis Stratifies Therapeutic Response

Author

Lai, D., primary, Funez-dePagnier, G., additional, Duenas-Bianchi, L., additional, Lavergne, A., additional, Battat, R., additional, Ahmed, W., additional, Schwartzman, M., additional, Lima, S., additional, Khan, S., additional, Chong, P.S., additional, Sonnenberg, G., additional, Artis, D., additional, Lukin, D., additional, Scherl, E., additional, and Longman, R.S., additional

Published
2022
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11. OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study

Author

Irving, P M, primary, Sands, B E, additional, Hoops, T, additional, Izanec, J L, additional, Gao, L L, additional, Gasink, C, additional, Greenspan, A, additional, Allez, M, additional, Danese, S, additional, Hanauer, S B, additional, Jairath, V, additional, Kuehbacher, T, additional, Lewis, J D, additional, Loftus, E V, additional, Mihaly, E, additional, Panaccione, R, additional, Scherl, E, additional, Shchukina, O, additional, and Sandborn, W J, additional

Published
2021
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12. DOP86 Corticosteroid-sparing effects of ustekinumab therapy for Ulcerative Colitis through 3 years: UNIFI long-term extension

Author

Scherl, E J, primary, Rowbotham, D S, additional, Danese, S, additional, Sandborn, W J, additional, Miao, Y, additional, Zhang, H, additional, Abreu, M T, additional, Panaccione, R, additional, Afif, W, additional, Hisamatsu, T, additional, Leong, R W, additional, Arasaradnam, R P, additional, Sands, B E, additional, and Marano, C, additional

Published
2021
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13. P508 Dose adjustment in patients with moderate to severe ulcerative colitis: results from year 3 of the UNIFI maintenance study long-term extension

Author

Rowbotham, D S, primary, Scherl, E J, additional, Sands, B E, additional, Panaccione, R, additional, Peyrin-Biroulet, L, additional, Zhang, H, additional, Miao, Y, additional, Leong, R W, additional, Afif, W, additional, Arasaradnam, R P, additional, Danese, S, additional, and Marano, C, additional

Published
2021
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14. DOP83 Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension

Author

Abreu, M T, primary, Danese, S, additional, Sandborn, W J, additional, Miao, Y, additional, Tikhonov, I, additional, Zhang, H, additional, Panaccione, R, additional, Hisamatsu, T, additional, Scherl, E J, additional, Leong, R W, additional, Rowbotham, D S, additional, Arasaradnam, R P, additional, Afif, W, additional, Peyrin-Biroulet, L, additional, Sands, B E, additional, and Marano, C, additional

Published
2021
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16. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis

Author

Sands, B. E., Sandborn, W. J., Panaccione, R., O'Brien, C. D., Zhang, H., Johanns, J., Adedokun, O. J., Li, K., Peyrin-Biroulet, L., Van Assche, G., Danese, S., Targan, S., Abreu, M. T., Hisamatsu, T., Szapary, P., Brown S, Marano C., Connor, S, De Cruz, P, Ding, Nj, Florin, T, Hendy, P, Leong, R, Moore, G, Pavli, P, Sparrow, M, Gassner, S, Vogelsang, H, Baert, F, Colard, A, De Vos, M, D'Heygere, F, Ferrante, M, Louis, E, Staessen, D, Berova, T, Churchev, J, Draganova, R, Gancheva, D, Ivanova, N, Marinova, I, Markov, M, Nikolov, R, Tsonev, N, Vassileva, G, Afif, W, Berstein, C, Bressler, B, Jairath, V, Lachance, Jr, Singh, R, Tilbe, K, Komarek, V, Kozeluhova, J, Lukas, M, Volfova, M, Dahlerup, J, Altwegg, R, Beorchia, S, Bouguen, G, Cadiot, G, Dupas, Jl, Desreumaux, P, Flourie, B, Grimaud, Jc, Guillaud, O, Moreau, J, Roblin, X, Zerbib, F, Baumgart, D, Beckebaum, S, Bokemeyer, B, Ebert, M, Hasselblatt, P, Lügering, A, Maaser, C, Schiefke, I, Schreiber, S, Seidler, U, Altorjay, I, Kiss, Gg, Literati-Nagy, B, Patai, A, Pecsi, G, Salamon, A, Schnabel, R, Székely, A, Tulassay, Z, Varga, M, Fich, A, Fishman, S, Konikoff, F, Lichtenstein, L, Rainis, T, Sbeit, W, Schwartz, D, Annese, V, Biancone, L, Bossa, F, Costintino, R, Danese, S, Fries, W, Gasbarrini, A, Guidi, L, Kohn, A, Maconi, G, Rocca, R, Rogai, F, Villa, E, Zoli, G, Akiho, H, Aoyama, N, Arisawa, T, Hidaka, H, Hisamatsu, T, Horiki, N, Inaba, T, Inoue, S, Ishida, T, Ishida, H, Ishiguro, Y, Ishihara, S, Iwabuchi, M, Kato, J, Katsushima, S, Kobayashi, T, Kojima, Y, Kurihara, H, Masuo, T, Matsui, T, Matsumoto, T, Matsuoka, K, Mitsuyama, K, Motoya, S, Nakagawa, T, Nakai, K, Nakamura, S, Niihara, T, Ohnishi, Y, Ohta, A, Osada, T, Ryuichi, I, Sakai, Y, Sakata, Y, Sameshima, Y, Sano, K, Shibatoge, M, Shibuya, T, Suzuki, Y, Takeshima, F, Tanaka, S, Taruishi, M, Tokito, S, Ueo, T, Watanabe, K, Yamagami, H, Cheon, Jh, Cho, Kb, Knowles, Kim, Kim, Hj, Kim, Y, Lee, Km, Yang, Sk, D'Haens, G, Pierik, M, Gearry, R, Inns, S, Rowbotham, D, Schultz, M, Bochenek, A, Gawdis-Wojnarska, B, Kleczkowski, D, Leszczyszyn, J, Malecka-Panas, E, Mamos, A, Petryka, R, Regula, J, Rozciecha, J, Stefanuik, P, Wozniak-Stolarska, B, Cimpoeru, N, Craciun, E, Ovidiu, Cf, Goldis, E, Ionita-Radu, F, Lazar, D, Suciu, I, Abdulkhakov, R, Alikhanov, B, Apartsin, K, Bakulin, I, Belousova, E, Gofman, A, Grinevich, V, Kulyapin, A, Nizov, A, Osipenko, M, Simanenkov, V, Tkachev, A, Uspenskiy, Y, Valuyskikh, E, Jovanovic, I, Nagorni, A, Svorcan, P, Zdravkovic, N, Bunganic, I, Abrahamovych, O, Bilianskyi, L, Datsenko, O, Golovchenko, O, Kharchenko, N, Klymenko, V, Levchenko, O, Lozynskyy, Y, Murenets, N, Oliinyk, O, Prystupa, L, Pyrogovskyi, V, Reznikova, V, Rishko, I, Stanislavchuk, M, Vizir, V, Yatsyshyn, R, Arasaradnam, R, Bloom, S, Cummings, F, Iqbal, T, Irving, P, Kaser, A, Shonde, A, Subramanian, S, Aberra, F, Aguilar, H, Araya, V, Bakken, A, Beaulieu, D, Cappa, Ja, Chiorean, M, Cohen, N, Dryden, G, Duvall, G, Ehrlich, A, Eisner, M, Ertan, A, Fogel, R, Friedenberg, K, Gatof, D, Glover, S, Grosman, I, Gunaratnam, N, Gupta, N, Haynes, P, Hemaidan, A, Higgins, P, Hou, J, Hudesman, D, Iskandar, H, Jazrawi, S, Jones, M, Karnam, U, Khurana, S, Killpack, M, Kreines, M, Lawlor, G, Lee, S, Loftus, E, Lukin, Dj, Marcet, J, Mattar, M, Melmed, G, Minor, T, Mirkin, K, Mutlu, E, Nichols, M, Nudell, J, Rai, R, Ramos, C, Mcleod, Randall, Rausher, D, Ritter, T, Singh Saini, S, Salzberg, B, Saubermann, L, Scherl, E, Sedghi, S, Sellin, J, Shafran, I, Sorrentino, D, Suiter, D, Swaminath, A, Tiongco, F, Vrabie, R, Walp, K, Warner, N, Winstead, N, Wolf, Dc, Woods, J, Yen, E, Younes, Z., Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Maag Darm Lever (9), Interne Geneeskunde, Sands, Be, Sandborn, Wj, Panaccione, R, O'Brien, Cd, Zhang, H, Johanns, J, Adedokun, Oj, Li, K, Peyrin-Biroulet, L, Van Assche, G, Danese, S, Targan, S, Abreu, Mt, Hisamatsu, T, Szapary, P, and Marano, C

Subjects
Adult, Male, Infusions, [SDV]Life Sciences [q-bio], Injections, Subcutaneous, Anti-Inflammatory Agents, Ulcerative, Klinikai orvostudományok, Article, Injections, Maintenance Chemotherapy, Dose-Response Relationship, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, INFLIXIMAB, Colitis, Ulcerative, Dose-Response Relationship, Drug, Female, Humans, Induction Chemotherapy, Infusions, Intravenous, Patient Acuity, Remission Induction, Ustekinumab, ComputingMilieux_MISCELLANEOUS, ACTIVITY INDEXES, Subcutaneous, Orvostudományok, General Medicine, EFFICACY, Colitis, 3. Good health, INFECTIONS, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Drug, Intravenous
Abstract

The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore1 [range, 0 to 3] on any of the four Mayo scale components).The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).

Published
2019
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20. P448 Dose adjustment in patients with moderate-to-severe ulcerative colitis: results from the UNIFI maintenance study long-term extension

Author

Danese, S, primary, Panaccione, R, additional, Peyrin-Biroulet, L, additional, Marano, C, additional, O’Brien, C D, additional, Zhang, H, additional, Zhou, Y, additional, Johanns, J, additional, Scherl, E, additional, Leong, R W L, additional, Rowbotham, D S, additional, Arasaradnam, R P, additional, and Sands, B E, additional

Published
2020
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21. P446 Transcriptional and microbial biomarkers of response to anti-TL1A therapy in ulcerative colitis: the Phase 2a TUSCANY study

Author

Hassan-Zahraee, M, primary, Ye, Z, additional, Xi, L, additional, Baniecki, M L, additional, Li, X, additional, Farin, W, additional, Tibaldi, L, additional, Allegretti, J R, additional, Romatowski, J, additional, Scherl, E J, additional, Klopocka, M, additional, Hyde, C, additional, Danese, S, additional, Longman, R, additional, and Hung, K E, additional

Published
2020
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22. DOP72 Safety, tolerability and efficacy of anti-TL1A antibody PF-06480605 in treatment of ulcerative colitis: The open-label, multicentre, Phase 2a TUSCANY study

Author

Danese, S, primary, Klopocka, M, additional, Scherl, E J, additional, Romatowski, J, additional, Allegretti, J R, additional, Peeva, E, additional, Vincent, M S, additional, Schoenbeck, U, additional, Xi, L, additional, Ye, Z, additional, Hassan-Zahraee, M, additional, Rath, N, additional, Li, G, additional, Neelakantan, S, additional, Banfield, C, additional, Lepsy, C, additional, Chandra, D, additional, and Hung, K E, additional

Published
2020
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23. P565 Efficacy and safety of long-term treatment with ustekinumab in moderate–severe ulcerative colitis patients with delayed response to ustekinumab induction: Results from UNIFI 2-year long-term extension

Author

Sands, B E, primary, Abreu, M T, additional, Leong, R W L, additional, Marano, C, additional, O’Brien, C D, additional, Zhang, H, additional, Zhou, Y, additional, Johanns, J, additional, Rowbotham, D, additional, Hisamatsu, T, additional, Arasaradnam, R P, additional, Scherl, E, additional, Danese, S, additional, and Peyrin-Biroulet, L, additional

Published
2020
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24. P729 The SAPPHIRE registry: Safety of immunosuppression in a prospective cohort of inflammatory bowel disease patients with a HIstoRy of CancEr

Author

Axelrad, J, primary, Colombel, J F, additional, Scherl, E, additional, Lukin, D, additional, Chang, S, additional, Chen, L, additional, Kwah, J, additional, Swaminath, A, additional, Sultan, K, additional, Lawlor, G, additional, Villagra, C, additional, Galanko, J, additional, Sharpless, V, additional, and Itzkowitz, S, additional

Published
2020
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27. DOP76 Corticosteroid sparing effects of ustekinumab therapy for ulcerative colitis through 2 years: UNIFI long-term extension

Author

Peyrin-Biroulet, L, primary, Sandborn, W, additional, Sands, B, additional, Scherl, E, additional, Marano, C, additional, O’Brien, C, additional, Zhang, H, additional, Johanns, J, additional, Zhou, Y, additional, Abreu, M, additional, Arasaradnam, R P, additional, Rowbotham, D S, additional, Leong, R W L, additional, and Danese, S, additional

Published
2020
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28. Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease

Author

Sandborn, Wj, Feagan, Bg, Rutgeerts, P, Hanauer, S, Colombel, Jf, Sands, Be, Lukas, M, Fedorak, Rn, Lee, S, Bressler, B, Fox, I, Rosario, M, Sankoh, S, Xu, J, Stephens, K, Milch, C, Parikh, A, Bampton P, GEMINI 2 Study G. r. o. u. p., Borody, T, Chung, A, Debinski, H, Florin, T, Hetzel, D, Jakobovits, S, Lawrance, I, Leong, R, Macrae, F, Mitchell, B, Moore, G, Pavli, P, Samuel, D, Weltman, M, Haas, T, Reinisch, W, Vogel, W, Baert, F, De Maeyer, M, De Vos, M, Dewit, O, D'Haens, G, Louis, E, Muls, V, Van Assche, G, Krastev, Z, Nikolovska, D, Petrov, P, Petrov, A, Stoinov, S, Tchernev, K, Vasileva, G, Aumais, G, Axler, J, Bailey, R, Bernstein, C, Bitton, A, Bourdages, R, Cohen, A, Devroede, G, Dhalla, S, Feagan, B, Fedorak, R, Green, D, Greenberg, G, Jones, J, Larkai, E, Macintosh, D, Panaccione, R, Ponich, T, Singh, R, Sy, R, Wiesinger, H, Albin, A, Douda, L, Horny, I, Stehlik, J, Stuksa, J, Volfova, M, Vyhnalek, P, Zadorova, Z, Andersen, V, Bendtsen, F, Fallingborg, J, Rannem, T, Maelt, A, Margus, B, Salupere, R, Allez, M, Des Varennes SB, Desreumaux, P, Dupas, Jl, Grimaud, Jc, Hebuterne, X, Lerebours, E, Picon, L, Zerbib, F, Aldinger, V, Baumgart, D, Buening, C, Dollinger, M, Hoffmann, P, Howaldt, S, Klaus, J, Konturek, Jw, Krummenerl, T, Malfertheiner, P, Schmidt, W, Schreiber, S, Seidler, U, Stallmach, A, Stremmel, W, Zeitz, M, Mantzaris, G, Triantafyllou, K, Ng, C, Bene, L, Fazekas, I, Fejes, R, Gall, J, Horvat, G, Hunyady, B, Salamon, A, Toth, T, Tulassay, Z, Varga, E, Varga, M, Varga Szabo, L, Vincze, A, Oddsson, E, Örvar, K, Ahuja, V, Amarapurkar, D, Chandra, A, Koshy, A, Krishna, P, Ramakrishna, K, Reddy, N, Thorat, V, Patchett, S, Ryan, B, Ben Horin, S, Fishman, S, Lavy, A, Rachmilewitz, D, Ardizzone, S, Corazziari, E, Danese, S, Fries, Walter, Gasbarrini, A, Kohn, A, Sturniolo, Gc, Danilans, A, George, Am, Hilmi, In, Engels, Lg, Ponsioen, Cy, van der Woude CJ, Gearry, R, Haines, M, Schultz, M, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Horynski, M, Huk, J, Jamrozik Kruk, Z, Janke, A, Klupinska, G, Marecik, J, Paradowski, L, Rudzinski, J, Rydzewska, G, Han, Ds, Hong, Sp, Kim, Hj, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Gheorghe, Ls, Voiosu, Rm, Alexeeva, O, Baranovsky, A, Bunkova, E, Burnevich, E, Dolgikh, O, Grinevich, V, Lakhin, A, Tarabar, D, Ling, Kl, Bunganic, I, Cernok, S, Gregus, M, Coetzer, T, Grundling, H, Moola, Sa, Wright, Jp, Ziady, C, Bermejo, F, Calvet, X, Herrerias, Jm, Perez Calle JL, Perez Gisbert, J, Hertervig, E, Karlen, P, Michetti, P, Rogler, G, Seibold, F, Wu, Dc, Atug, O, Kurdas, Oo, Datsenko, O, Dorofyeyev, A, Dudar, L, Golovchenko, O, Klyarits'Ka, I, Skrypnyk, I, Hawthorne, Ab, Middleton, S, Abreu, M, Bala, N, Becker, S, Behm, B, Braun, R, Bukhari, M, Chen, S, Coates, A, Dar, S, Dassopoulos, T, De Villiers, W, Desautels, S, Desta, T, Dimitroff, J, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glombicki, A, Glover, S, Gordon, G, Grisolano, S, Hanson, J, Hardi, R, Hoffman, B, Isaacs, K, Kim, C, Koval, G, Lashner, B, Lawitz, E, Leman, B, Levine, J, Loftus, E, Mahadevan, U, Mannon, P, Marcet, J, Matsuyama, R, Matusow, G, Mccabe, R, Mirkin, K, Murphy, M, Mushahwar, A, Mutlu, E, Nagrani, M, Nguyen, D, Nichols, M, Nieves Ramirez, A, Oubre, B, Pace, S, Pandak, W, Perera, L, Quadri, A, Quallich, L, Rajapakse, R, Randall, C, Regueiro, M, Safdi, A, Sandborn, W, Sands, B, Saubermann, L, Scherl, E, Schwartz, D, Sedghi, S, Shafran, I, Shepard, R, Siegel, C, Stein, L, Tatum, H, Triebling, A, Vasudeva, R, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Lev, M., GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., and Medical Microbiology & Infectious Diseases

Subjects
Adult, Male, Integrins, medicine.medical_specialty, HUMAN POLYOMAVIRUSES, JC, Antibodies/blood, Antibodies, Monoclonal, Humanized/adverse effects, Antibodies, Monoclonal, Humanized/immunology, Crohn Disease/drug therapy, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Glucocorticoids/therapeutic use, Humans, Immunosuppressive Agents/therapeutic use, Induction Chemotherapy, Infusions, Intravenous/adverse effects, Integrins/antagonists & inhibitors, Integrins/immunology, Maintenance Chemotherapy, Middle Aged, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, Antibodies, Monoclonal, Humanized, Placebo, Gastroenterology, Inflammatory bowel disease, Antibodies, Vedolizumab, CERTOLIZUMAB PEGOL, Natalizumab, Crohn Disease, Maintenance therapy, HUMANIZED ANTIBODY, Internal medicine, Ustekinumab, medicine, Certolizumab pegol, Infusions, Intravenous, Glucocorticoids, NATALIZUMAB, business.industry, Induction chemotherapy, General Medicine, medicine.disease, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, RELAPSING MULTIPLE-SCLEROSIS, INFLAMMATORY-BOWEL-DISEASE, HUMAN POLYOMAVIRUSES, HUMANIZED ANTIBODY, CERTOLIZUMAB PEGOL, ULCERATIVE-COLITIS, RANDOMIZED-TRIAL, NATALIZUMAB, JC, RANDOMIZED-TRIAL, digestive system diseases, Surgery, ULCERATIVE-COLITIS, RELAPSING MULTIPLE-SCLEROSIS, business, Immunosuppressive Agents, INFLAMMATORY-BOWEL-DISEASE, medicine.drug
Abstract

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P

Published
2013
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29. Risk Stratification for Prevention of Recurrence of Postoperative Crohn’s Disease

Author

Shirley Cohen-Mekelburg, Schneider, Y., Gold, S., Scherl, E., and Steinlauf, A.

Subjects
Column
Abstract

Although there have been significant advances in medical therapies to treat Crohn's disease, an estimated 50% of patients will require surgery within the first decade of disease duration. Of these patients, a substantial number will develop recurrent symptoms within the first postoperative year. To prevent disease recurrence, many physicians use postoperative prophylactic therapy. Randomized, controlled trials, although limited in number, have demonstrated that a prophylactic postoperative strategy is effective at reducing recurrence (both clinical and endoscopic) in high-risk patients. This article reviews the frequency of and risk factors for postoperative Crohn's disease recurrence and the current evidence in favor of postoperative Crohn's disease management strategies. Future studies must be conducted to establish a gold standard as to who should receive postoperative prophylaxis and which therapies and time course are ideal.

Published
2017

32. Ustekinumab as induction and maintenance therapy for Crohn's disease

Author

Feagan, Bg, Sandborn, Wj, Gasink, C, Jacobstein, D, Lang, Y, Friedman, Jr, Blank, Ma, Johanns, J, Gao, Ll, Miao, Y, Adedokun, Oj, Sands, Be, Hanauer, Sb, Vermeire, S, Targan, S, Ghosh, S, de Villiers WJ, Colombel, Jf, Tulassay, Z, Seidler, U, Salzberg, Ba, Desreumaux, P, Lee, Sd, Loftus EV Jr, Dieleman, La, 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, Dieleman, L, Feagan, B, 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, Lügering, 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 CJ, 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, Hanauer, S, Hanson, J, Hardi, R, Higgins, P, Isaacs, K, Katz, J, Kaur, N, Khan, N, Lee, S, Leman, B, Levenson, S, Lichtiger, S, Loftus, E, 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, Salzberg, B, Sandborn, W, 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, Banić, M, Duvnjak, M, Stimac, D, Goujon, G, Pelletier, A, Peyrin-Biroulet, L, Aldinger, V, Bokemeyer, B, Büning, C, Konturek, J, Krummenerl, T, Ochsenkuehn, T, Altorjay, I, Kis, J, Pecsi, G, Székely, 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, Gc, Horiki, N, Iijima, H, Iwabuchi, M, Kanai, T, Kunisaki, R, Maemoto, A, Matsuoka, K, Osada, T, Sugimoto, K, Tanaka, S, Cheon, Jh, Han, Ds, Jang, Bi, Kim, Hj, Kim, Js, Kim, Yh, Park, Sj, Yang, Sk, 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, Fc, Prins, M, Watermeyer, G, Ziady, C, Calvo, Xc, Domínguez-Muñoz, Je, Gisbert, Jp, 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, Khan, Nh, Khurana, S, Legnani, P, Mutlu, E, Phillips, R, Rai, R, Reichelderfer, M, Ritter, T, Safdi, Ma, Sands, B, Schulman, M, Smith, J, Suiter, D, Taylor, D, Vasudeva, R, Winstead, T, Zwick, A, Savoye, G, Atreya, R, Ochsenkuhn, T, Ott, C, Goldin, E, Motohiro, E, Takanori, K, Park, S, 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, and UNITI-IM-UNITI Study Group

Subjects
030203 arthritis & rheumatology, Adult, Male, Infusions, Medicine (all), Remission Induction, Crohn Disease, Female, Humans, Induction Chemotherapy, Infusions, Intravenous, Maintenance Chemotherapy, Middle Aged, Ustekinumab, General Medicine, Orvostudományok, Klinikai orvostudományok, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Intravenous
Abstract

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.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 score150). The primary end point for the maintenance trial was remission at week 44 (CDAI score150).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 P0.001 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.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. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).

Published
2016

33. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn’s Disease After Ileocolonic Resection

Author

Regueiro, Miguel, primary, Feagan, Brian G., additional, Zou, Bin, additional, Johanns, Jewel, additional, Blank, Marion A., additional, Chevrier, Marc, additional, Plevy, Scott, additional, Popp, John, additional, Cornillie, Freddy J., additional, Lukas, Milan, additional, Danese, Silvio, additional, Gionchetti, Paolo, additional, Hanauer, Stephen B., additional, Reinisch, Walter, additional, Sandborn, William J., additional, Sorrentino, Dario, additional, Rutgeerts, Paul, additional, Debinski, H., additional, Florin, T., additional, Hetzel, D., additional, Lawrance, I., additional, Radford-Smith, G., additional, Sloss, A., additional, Sorrentino, D., additional, Gassner, S., additional, Haas, T., additional, Reicht, G., additional, Reinisch, W., additional, Strasser, M., additional, Vogelsang, H., additional, Bossuyt, P., additional, DeWit, O., additional, D'Haens, G., additional, Franchimont, D., additional, Louis, E., additional, Vermeire, S., additional, Bernstein, C.N., additional, Bourdages, R., additional, Chiba, N., additional, Dhalla, S.S., additional, Feagan, B.G., additional, Fedorak, R.N., additional, Lachance, J.R., additional, Panaccione, R., additional, Ropeleski, M., additional, Singh Salh, B., additional, Lukas, M, additional, Colombel, J-F, additional, Allez, M., additional, Desreumaux, P., additional, Dupas, J.L., additional, Grimaud, J-C., additional, Hebuterne, X., additional, Laharie, D., additional, Lerebours, E., additional, Peyrin-Biroulet, L., additional, Reimund, J-M., additional, Viennot, S., additional, Zerbib, F., additional, Antoni, C., additional, Atreya, R., additional, Baumgart, D.C., additional, Berg, C., additional, Boecker, U., additional, Bramkamp, G., additional, Bünning, C., additional, Ehehalt, R., additional, Howaldt, S., additional, Kucharzik, T., additional, Lamprecht, H.G., additional, Mudter, J., additional, Preiss, J.C., additional, Schreiber, S., additional, Seidler, U., additional, Altorjay, I., additional, Banai, J., additional, Lakatos, P.L., additional, Varga, M., additional, Vincze, A., additional, Avni-Biron, I., additional, Fishman, S., additional, Fraser, G.M., additional, Goldin, E., additional, Rachmilewitz, D., additional, Annese, V., additional, Ardizzone, S., additional, Biancone, L., additional, Bossa, F., additional, Danese, S., additional, Fries, W., additional, Gionchetti, P., additional, Maconi, G., additional, Terrosu, G., additional, Usai, P., additional, D'Haens, G.R., additional, Gearry, R.B., additional, Hill, J., additional, Rowbotham, D.S., additional, Schultz, M., additional, Stubbs, R.S., additional, Wallace, D., additional, Walmsley, R.S., additional, Wyeth, J., additional, Malecka-Panas, E., additional, Paradowski, L., additional, Regula, J., additional, Beales, I.P., additional, Campbell, S., additional, Hawthorne, A.B., additional, Parkes, M., additional, Travis, S.P., additional, Achkar, J.P., additional, Behm, B.W., additional, Bickston, S.J., additional, Brown, K.J., additional, Chiorean, M.V., additional, DeVilliers, W.J.S., additional, Elliott, D.E., additional, Grunkmeier, D., additional, Hamilton, J.W., additional, Hanauer, S.B., additional, Hanson, J.S., additional, Hardi, R., additional, Helper, D.J., additional, Herfarth, H., additional, Higgins, P.D.R., additional, Holderman, W.H., additional, Kottoor, R., additional, Kreines, M.D., additional, Leman, B.I., additional, Li, X., additional, Loftus, E.V., additional, Noar, M., additional, Oikonomou, I., additional, Onken, J., additional, Peterson, K.A., additional, Phillips, R.P., additional, Randall, C.W., additional, Ricci, M., additional, Ritter, T., additional, Rubin, D.T., additional, Safdi, M., additional, Sandborn, W.J., additional, Sauberman, L., additional, Scherl, E., additional, Schwarz, R.P., additional, Sedghi, S., additional, Shafran, I., additional, Sninsky, C.A., additional, Stein, I., additional, Swoger, J., additional, Vecchio, J., additional, Weinberg, D.I., additional, Wruble, L.D., additional, Yajnik, V., additional, and Younes, Z., additional

Published
2016
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34. Vedolizumab as induction and maintenance therapy for ulcerative colitis

Author

Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, Parikh, A, Bampton P, GEMINI 1 Study G. r. o. u. p., Chung, A, Debinski, H, Florin, T, Hetzel, D, Kronborg, I, Lawrance, I, Leong, R, Macrae, F, Moore, G, Pavli, P, Radford Smith, G, Weltman, M, Haas, T, Reinisch, W, Stockenhuber, F, Vogel, W, De Maeyer, M, De Vos, M, D'Haens, G, Louis, E, Muls, V, Petrov, P, Aumais, G, Bitton, A, Bourdages, R, Bressler, B, Cohen, A, Fedorak, R, Greenberg, G, Jones, J, Kutcher, W, Macintosh, D, Ponich, T, Singh, R, Steinhart, H, Sy, R, Douda, L, Lukas, M, Samek, M, Vyhnalek, P, Woznica, V, Zadorova, Z, Andersen, V, Rannem, T, Staun, M, Maelt, A, Margus, B, Bonaz, B, Coffin, B, Desreumaux, P, Laharie, D, Reimund, Jm, Karaus, M, Pace, A, Ross, M, Schmidt, W, Witthoeft, T, Zeitz, M, Karamanolis, D, Mantzaris, G, Maris, T, Ng, C, Gall, J, Hunyady, B, Szepes, A, Toth, T, Vincze, A, Oddsson, E, Jósefsspktali, Kö, Ahuja, V, Amarapurkar, D, Goenka, M, Habeeb, Ma, Jalihal, U, Kalambe, B, Koshy, A, Kumar, R, Prasad, V, Reddy, N, Sekar, T, Shankar, R, Tantry, V, Ryan, B, Avni, Y, Ben Horin, S, Ardizzone, S, Armuzzi, A, Corazziari, E, Fries, Walter, Kohn, A, Lisova, D, George, Am, Hilmi, In, Bhaskaran, Sk, Soon, Sy, Engels, L, Ponsioen, C, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Huk, J, Jamrozik Kruk, Z, Kondusz Szklarz, M, Paradowski, L, Wiechowska Kozlowska, A, Han, Ds, Hong, Sp, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Alexeeva, O, Bunkova, E, Burnevich, E, Dolgikh, O, Kasherininova, I, Khovaeva, Y, Lakhin, A, Ling, Kl, Bester, F, Coetzer, T, Grundling Hde, K, Jackson, Ld, Spies, P, Wright, Jp, Ziady, C, Garcia Planella, E, Perez Gisbert, J, Rogler, G, Seibold, F, Kao, Aw, Wu, Dc, Atug, O, Kurdas, Oo, Hawthorne, Ab, Lindsay, J, Abreu, M, Aggarwal, A, Bala, N, Becker, S, Behm, B, Braun, R, Cohn, W, Cross, R, Dar, S, Dassopoulos, T, De Villiers, W, Desta, T, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glover, S, Gopal, V, Hanson, J, Hardi, R, Isaacs, K, Jain, R, Karyotakis, N, Korzenik, J, Koshy, G, Koval, G, Lawitz, E, Lee, S, Loftus, E, Luther, R, Mahadevan, U, Mannon, P, Matsuyama, R, Mcintosh, A, Melmed, G, Mirkin, K, Nichols, M, Oubre, B, Pandak, W, Quadri, A, Quallich, L, Randall, C, Rausher, D, Regueiro, M, Safdi, A, Sands, B, Scherl, E, Schneier, J, Schwartz, D, Sedghi, S, Shafran, I, Siegel, C, Stein, L, Tatum, H, Weinberg, D, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Abstract, Lev M., Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, and Parikh, A

Subjects
Adult, Male, medicine.medical_specialty, Integrins, Placebo, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, law.invention, Vedolizumab, Maintenance Chemotherapy, Maintenance therapy, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Glucocorticoids, Aged, business.industry, General Medicine, Induction Chemotherapy, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Surgery, Clinical trial, Cohort, Colitis, Ulcerative, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).

Published
2013
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35. Vedolizumab as induction and maintenance therapy for Crohn's disease.

Author

GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., Sandborn, W.J., Feagan, B.G., Colombel, J.F., Sands, B.E., Fedorak, R.N., Fox, I., Rosario, M., Sankoh, S., Xu, J., Stephens, K., Milch, C., Parikh, A., GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., Sandborn, W.J., Feagan, B.G., Colombel, J.F., Sands, B.E., Fedorak, R.N., Fox, I., Rosario, M., Sankoh, S., Xu, J., Stephens, K., Milch, C., and Parikh, A.

Abstract

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients rec

Published
2013

42. The cost-effectiveness of vedolizumab for inflammatory bowel disease: A review of the current literature

Author

Schneider, Y., Saumoy, M., Shirley Cohen-Mekelburg, Steinlauf, A. F., and Scherl, E. J.

Subjects
Column, health care economics and organizations
Abstract

The United States spends a greater share per gross domestic product on health care than any other developed country in the world. Cost-conscious, high-value care has an important role in the practice of medicine. Inflammatory bowel disease (IBD) affects 1.6 million people in the United States and is responsible for significant health care costs, with estimates as high as $31.6 billion annually, a large portion of which is attributable to the use of biologic therapies. As the number of therapeutic targets for IBD expands, gastroenterologists can anticipate the arrival of novel therapeutic agents on the market, and these may carry significant costs. Vedolizumab, a monoclonal antibody directed against the gut-selective integrin α4β7, is a novel biologic agent approved for the treatment of Crohn's disease and ulcerative colitis. Cost-effectiveness is an area of research that aims to assess the added value (in terms of both cost and utility) of diagnostic or therapeutic interventions. This article reviews the current literature evaluating the cost-effectiveness of vedolizumab for the treatment of IBD.

44. Wound Healing After Vaginal Delivery, Episiotomy, and Cesarean Section Delivery Among Women With IBD: Results From the PIANO Registry.

Author

Lewin S, Long M, Cohen R, Scherl E, Wolf D, and Mahadevan U

Abstract

Background: Women with inflammatory bowel disease (IBD) face complexities of disease management during pregnancy and childbirth. Apprehension regarding vaginal delivery in pregnant individuals with IBD persists due to concern for perianal disease and perineal trauma. The incidence of poor wound healing after obstetric anal sphincter injury is approximately 4% in the general population. In an IBD population, risk of developing and difficulty healing perineal tears and episiotomy is not well described., Methods: In a multicenter prospective cohort of pregnant individuals with IBD, we collected demographic information, IBD disease and treatment history, pregnancy and labor history, and reports of delayed wound healing >1 month from episiotomy, vaginal tear, or Cesarean (C-) section. Prospective data were collected using questionnaires that were administered each trimester of pregnancy, at delivery, and in the year postpartum., Results: There were 743 patients in the PIANO registry who answered questions pertaining to postpartum wound healing, with 330 (44%) reporting a C-section and 413 (56%) reporting a vaginal delivery. Of 119 C-section deliveries assessed for delayed wound healing, only 1 (0.8%) patient reported this complication. Episiotomies were reported in 59 (14%) patients, with 9 (15%) reporting delayed wound healing. Vaginal tears were reported in 252 (64%) patients. Delayed wound healing from vaginal tear was reported in 9% of patients. Use of immunomodulators was associated with delayed wound healing from episiotomy (33% vs 0% for those on no medications, P = .024). No difference was seen in wound healing time for episiotomy with other medications, including corticosteroids, anti-tumor necrosis factor, or anti-integrin use. Delayed wound healing from vaginal tear was not associated with any class of IBD medication., Conclusions: Episiotomy was a common occurrence in patients with IBD. Immunomodulator, but not biologic, use was found to be associated with delayed wound healing. This association could reflect a direct medication effect on episiotomy wound healing or inadequate treatment of underlying active disease prior to delivery. Vaginal tears were also common but delayed wound healing was not associated with IBD therapy. C-section occurred at high rates, particularly in Crohn's disease patients, with no reported delays in postpartum wound healing., (© The Author(s) 2025. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2025
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45. Predictive Model for Outcomes in Inflammatory Bowel Disease Patients Receiving Maintenance Infliximab Therapy.

Author

Wong R, Charilaou P, Hemperly A, Qin L, Pan Y, Mathani P, Longman R, Boland BS, Dulai PS, Holmer AK, Lukin D, Singh S, Valasek MA, Sandborn WJ, Scherl E, Vande Casteele N, and Battat R

Abstract

Background: No models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes., Methods: Adult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included. The primary endpoint was an unfavorable outcome of active objective inflammation or need for IBD-related surgery or hospitalization at 6-18 months follow-up. Internal variables were identified using univariable analyses, modeling used multivariable analysis, and performance was assessed (area under receiver-operating curve [AUC]) and externally validated., Results: In 81 patients, 40.7% developed unfavorable outcomes at follow-up. Infliximab concentration <9.3 µg/mL (odds ratio [OR] 5.3, P  = .001) and RHI > 12 (OR 3.4, P  = .03) were the only factors associated with developing the primary unfavorable outcome. A prediction score assigning 1 point to each variable had good discrimination and performed similarly on internal (AUC 0.71) and external (AUC 0.73) cohorts. The risk of primary unfavorable outcomes in internal and external cohorts, respectively, was 23% and 15% for a score of 0, 46% and 50% for a score of 1, and 100% and 75% for a score of 2. Infliximab concentration alone performed similar to the 2-predictor model in internal (AUC 0.65, P  = .5 vs. 2-predictor model) and external (AUC 0.70, P  = .9, vs. 2-predictor model) cohorts., Conclusions: Using unbiased variable selection, a 2-predictor model using infliximab concentrations and histology identified IBD patients on maintenance infliximab therapy at high risk of future unfavorable outcomes. For practical applicability, infliximab concentrations alone performed similarly well., Competing Interests: R.L.: Consulting for Pfizer. B.S.B.: Consulting for Bristol Meyers Squibb, Takeda, Pfizer. Grants: Gilead, Prometheus Biosciences. B.S.B. holds the position of Clinical Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. P.S.D.: Consulting and/or research support from Takeda, Pfizer, Abbvi, Janssn, Gilead, BMS, Abivax, Addiso, GSK, Lilly. A.K.H.: Received advisory board fees from Pfizer. D.L.: Consulting for Abbvie, Boehringer Ingelheim, Bristol Meyers Squibb, Eli Lilly, Janssen, Palatin Technologies, Pfizer, Prometheus Laboratories. Grants: Abbvie, Janssen, Takeda. S.S.: Research grants from AbbVie and Pfizer in the previous 24 months; personal fees from Pfizer for ad hoc grant review. W.J.S.: research grants from Abbvie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Laboratories, Seres Therapeutics, Shire Pharmaceuticals, Takeda, Theravance Biopharma; consulting fees from Abbvie, Abivax, Alfasigma, Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust), Allakos, Amgen, Arena Pharmaceuticals, AstraZeneca, Atlantic Pharmaceuticals, Beigene, Boehringer Ingelheim, Bristol Meyers Squibb, Celltrion, Clostrabio, Forbion, Galapagos, Genentech (Roche), GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Iota Biosciences, Janssen, Lilly, Morphic Therapeutics, Novartis, Oppilan Pharma (now Ventyx Biosciences), Pfizer, Pharm Olam, Polpharm, Progenity, Prometheus Biosciences, Protagonist Therapeutics, PTM Therapeutics, Seres Therapeutics, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Vedanta Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences, Xencor, Zealand Pharmaceuticals; stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma (now Ventyx Biosciences), Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences; and employee at Shoreline Biosciences and Ventyx Biosciences. Spouse: Iveric Bio—consultant, stock options; Progenity—stock; Oppilan Pharma (now Ventyx Biosciences)—stock; Prometheus Biosciences—employee, stock, stock options; Prometheus Laboratories—stock, stock options, consultant; Ventyx Biosciences—stock, stock options; Vimalan Biosciences—stock, stock options. E.S.: Grant/Research Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech. Seres Therapeutics, Celgene Corporation; Consultant/Advisory Board: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb; Stock Shareholder: Gilead; Honoraria: GIHealth Foundation for non-branded speaker’s bureau, Janssen for non-branded speaker’s bureau. N.V.C.: received research grant from R-Biopharm; and personal fees from AcelaBio, Alimentiv, Pfizer, ProciseDX, and Ventyx. These activities were all outside of the submitted work. R.B.: Speaking/Consulting/Advertising Boards: Prometheus Laboratories, Bristol Myers Squibb, Janssen, Abbvie, Takeda, Pfizer, Eli Lilly. All other authors (R.W., P.C., A.H., L.Q., Y.P., P.M., M.A.V.) have no financial disclosures or conflicts of interest to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Published
2024
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46. The Relationship Between the Endoscopic Healing Index, Fecal Calprotectin, and Magnetic Resonance Enterography in Crohn's Disease.

Author

Smith ES, Chen J, Pan Y, Mahtani P, Lukin D, Ahmed W, Longman R, Burakoff R, Scherl E, and Battat R

Subjects
Humans, Male, Female, Adult, Prospective Studies, Middle Aged, Young Adult, Biomarkers analysis, Biomarkers metabolism, Ileum diagnostic imaging, Ileum pathology, Endoscopy, Gastrointestinal, ROC Curve, Crohn Disease diagnostic imaging, Leukocyte L1 Antigen Complex analysis, Feces chemistry, Magnetic Resonance Imaging methods, Severity of Illness Index
Abstract

Introduction: The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity., Materials and Methods: Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL., Results: A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P =0.002), FCAL >50 µg/g (87% vs. 64%, P <0.001) and FCAL >250 µg/g (90% vs. 75%, P =0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P <0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P =0.35)., Conclusion: Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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47. Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry.

Author

Itzkowitz SH, Jiang Y, Villagra C, Colombel JF, Sultan K, Lukin DJ, Faleck DM, Scherl E, Chang S, Chen L, Katz S, Kwah J, Swaminath A, Petralia F, Sharpless V, Sachar D, Jandorf L, and Axelrad JE

Abstract

Background & Aims: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue., Methods: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications., Results: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class., Conclusions: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2024
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48. Higher Adalimumab Trough Levels Are Associated with Histologic Remission and Mucosal Healing in Inflammatory Bowel Disease.

Author

Wong R, Qin L, Pan Y, Mahtani P, Longman R, Lukin D, Scherl E, and Battat R

Abstract

(1) Many patients with inflammatory bowel disease (IBD) in endoscopic remission have persistent histologic activity, which is associated with worse outcomes. There are limited data on the association between adalimumab drug concentrations and histologic outcomes using validated histologic indices. We aimed to assess the relationship between adalimumab concentrations and the Robarts Histopathology Index (RHI). (2) Patients from a tertiary IBD center from 2013 to 2020 with serum adalimumab (ADA) trough concentrations measured during maintenance therapy (≥14 weeks) and a colonoscopy or flexible sigmoidoscopy with biopsies performed within 90 days of drug level were included. Blinded histologic scoring using the RHI was performed. Primary analysis assessed the relationship between adalimumab drug concentrations and histologic remission using receiver operating characteristic curve analysis. (3) In 36 patients (26 Crohn's Disease, 9 ulcerative colitis, 1 indeterminate), median adalimumab concentrations were higher (17.3 ug/mL, 12.2-24.0) in patients with histologic remission compared to those without (10.3 ug/mL, 6.8-13.9, p = 0.008). The optimal ADA concentration identified using the Youden threshold was ≥16.3 ug/mL (sensitivity 70%, specificity 90%). Patients with ADA ≥ 16.3 ug/mL had higher histologic remission rates (78%) compared to lower ADA concentrations (14%, p = 0.002), as well as higher mucosal healing rates (86%) compared to lower levels (12%, p = 0.001). Symptoms correlated weakly and non-significantly with both histologic (RHI) scores (r = 0.25, p = 0.2) and adalimumab concentrations (r = 0.05, p = 0.8). (4) The current study demonstrated that higher serum adalimumab concentrations (≥16.3 ug/mL) are needed for histologic remission and mucosal healing assessed using the RHI.

Published
2023
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50. The Impact of Confounders on Symptom-Endoscopic Discordances in Crohn's Disease.

Author

Rajan A, Pan Y, Mahtani P, Niec R, Longman R, Gerber J, Lukin D, Scherl E, and Battat R

Abstract

Background: Discordances between clinical and endoscopic Crohn's disease (CD) activity indices negatively impact the utility of clinic visits and efficacy assessments in clinical trials. Bile acid diarrhea (BAD) and small intestinal bacterial overgrowth (SIBO) mimic CD symptoms. This study quantified the impact of BAD and SIBO on the relationship between clinical and endoscopic disease activity indices., Methods: CD patients with 7α-hydroxy-4-cholesten-3-one (7C4) serum measurements and/or SIBO breath tests and matched clinical and endoscopic scores were included. Clinical remission (stool frequency [SF] ≤ 1 and abdominal pain score ≤ 1) rates were compared between those with and without (1) endoscopic remission, (2) BAD (7C4 > 55 ng/mL), and (3) SIBO., Results: Of 295 CD patients, 219 had SIBO testing and 87 had 7C4 testing. Patients with elevated 7C4 had lower proportions with clinical remission (14% vs 40%, P = .007) and SF ≤ 1 (14% vs 42%, P = .004) compared to those with normal 7C4. In patients with normal 7C4, higher rates of clinical remission (65% vs 27%, P = .01) and SF ≤ 1 (71% vs 27%, P = .003) existed in patients with endoscopic remission compared to those without endoscopic remission. Conversely, among the entire 295 patient cohorts, nearly identical clinical remission rates existed between those with and without endoscopic remission (25% vs 24%, P = .8), and the Crohn's Disease Patient-Reported Outcome-2 score was not accurate for predicting endoscopic remission (Area Under the Curve (AUC): 0.48; 95% CI, 0.42-0.55). SIBO status did not impact clinical remission rates ( P = 1.0)., Conclusions: BAD, but not SIBO, contributed to symptom scores. A relationship between endoscopic inflammation and clinical remission rates only existed in patients without 7C4 elevations., Competing Interests: A.R., Y.P., P.M., R.N., J.G.: no conflicts of interest to disclose. R.L.: Consulting/Speaking Fees: Pfizer, Enzymetrics, Ancilia Biosciences. Grant Support: National Institute of Health (NIH). D.L.: Consulting/Speaking Fees: Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Palatin Technologies, Pfizer. Grant Support: Abbvie, Janssen, Takeda. E.S.: Consulting/Speaking Fees: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Grant Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech, Seres Therapeutics, Celgen. R.B.: Consulting: Prometheus, (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Published
2023
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