Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy

U. Kopylov; J. Hanzel; C. Liefferinckx; D. De Marco; N. Imperatore; N. Plevris; I. Baston-Rey; R.J. Harris; M. Truyens; V. Domislovic; S. Vavricka; V. Biemans; S. Myers; S. Sebastian; S. Ben-Horin; Y.G. Lama; C. Gilletta; B.G.S. Ariella; Z. Zelinkova; R. Weishof; D. Storan; E. Zittan; K. Farkas; T. Molnar; D. Franchimont; A. Cremer; W. Afif; F. Castiglione; C. Lees; M. Barreiro-de Acosta; T. Lobaton; G. Doherty; Z. Krznaric; M. Pierik; F. Hoentjen; D. Drobne

doi:10.1111/apt.15784

Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy

U. Kopylov^*, J. Hanzel, C. Liefferinckx, D. De Marco, N. Imperatore, N. Plevris, I. Baston-Rey, R.J. Harris, M. Truyens, V. Domislovic, S. Vavricka, V. Biemans, S. Myers, S. Sebastian, S. Ben-Horin, Y.G. Lama, C. Gilletta, B.G.S. Ariella, Z. Zelinkova, R. WeishofD. Storan, E. Zittan, K. Farkas, T. Molnar, D. Franchimont, A. Cremer, W. Afif, F. Castiglione, C. Lees, M. Barreiro-de Acosta, T. Lobaton, G. Doherty, Z. Krznaric, M. Pierik, F. Hoentjen, D. Drobne

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited.Aim To assess the effectiveness of dose escalation of ustekinumab.Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

Original language	English
Pages (from-to)	135-142
Number of pages	8
Journal	Alimentary Pharmacology & Therapeutics
Volume	52
Issue number	1
DOIs	https://doi.org/10.1111/apt.15784
Publication status	Published - 1 Jul 2020

Keywords

experience
induction
EXPERIENCE
INDUCTION

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10.1111/apt.15784

Cite this

Kopylov, U., Hanzel, J., Liefferinckx, C., De Marco, D., Imperatore, N., Plevris, N., Baston-Rey, I., Harris, R. J., Truyens, M., Domislovic, V., Vavricka, S., Biemans, V., Myers, S., Sebastian, S., Ben-Horin, S., Lama, Y. G., Gilletta, C., Ariella, B. G. S., Zelinkova, Z., ... Drobne, D. (2020). Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy. Alimentary Pharmacology & Therapeutics, 52(1), 135-142. https://doi.org/10.1111/apt.15784

@article{96db50108872468889efcc762d22ce0f,

title = "Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy",

abstract = "Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited.Aim To assess the effectiveness of dose escalation of ustekinumab.Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.",

keywords = "experience, induction, EXPERIENCE, INDUCTION",

author = "U. Kopylov and J. Hanzel and C. Liefferinckx and {De Marco}, D. and N. Imperatore and N. Plevris and I. Baston-Rey and R.J. Harris and M. Truyens and V. Domislovic and S. Vavricka and V. Biemans and S. Myers and S. Sebastian and S. Ben-Horin and Y.G. Lama and C. Gilletta and B.G.S. Ariella and Z. Zelinkova and R. Weishof and D. Storan and E. Zittan and K. Farkas and T. Molnar and D. Franchimont and A. Cremer and W. Afif and F. Castiglione and C. Lees and {Barreiro-de Acosta}, M. and T. Lobaton and G. Doherty and Z. Krznaric and M. Pierik and F. Hoentjen and D. Drobne",

note = "Funding Information: Uri Kopylov, designed the study, collected the data, performed the analysis and drafted the manuscriptJurij Hanzel, Claire Liefferinckx, Davide De Marco, Nicola Imperatore, Nikolas Plevris, Iria Baston-Rey, Richard J Harris, Marie Truyens, Viktor Domislovic, Stephan Vavricka, Vince Biemans, Sally Myers, Shaji Sebastian, Shomron Ben- Horin, Yago Gonz?lez Lama, Cyrielle Gilletta, Bar-Gil Shitrit Ariella, Zuzana Zelinkova, Roni Weishof, Darragh Storan, Eran Zittan, Klaudia Farkas, Tamas Molnar, Denis Franchimont, Anneline Cremer, Waqqas Afif, Fabiana Castiglione, Charles Lees, Manuel Barreiro-de Acosta, Triana Lobaton, Glen Doherty, Zeljko Krznaric, Marieke Pierik, Frank Hoentjen, David Drobne, collected the data, reviewed the manuscript and contributed valuable scientific content. Declaration of personal interests: Uri Kopylov received consultancy and speaker fees from Abbvie, Janssen, Takeda, MSD and Medtronic, and research grants from Janssen Takeda Medtronic. Jurij Hanzel received lecture fees from Biogen, Janssen and Takeda outside the submitted work. Claire Liefferinckx received consultancy fees from Takeda, and speaker fees from Sandoz, Janssen, Abbvie. Anneline Cremer received consultancy fees from Takeda and Janssen, and speaker fees from Pfizer and Abbvie. Denis Franchimont received educational grants from Abbvie, Takeda, MSD, fees or consultancy fees from Ferring, Falk, Chiesi, Abbvie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma and Hospira. Zeljko Krznaric received speaker fees from Abbvie, Takeda, MSD, Janssen, Oktal Pharma, Fresenius, Mylan and Pfizer. Manuel Barreiro-de Acosta has served as a speaker, a consultant and advisory member for or received research funding from MSD, Abbvie, Celltrion, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Chiesi, Gebro Pharma, Roche, Otsuka Pharmaceuticals and Tillotts Pharma. Shomron Ben-Horin received consulting and advisory board fees and research support from AbbVie, Janssen, Takeda and Celltrion, and consulting and speaker fees from Pfizer, GlaxoSmithKline and MSD. Frank Hoentjen has served on advisory boards or as speaker or consultant for Abbvie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen-Cilag, Abbvie. Klaudia Farkas received speaker fees from AbbVie, Takeda, Janssen and Ferring. Tam?s Moln?r received speaker fees from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer and Teva. Eran Zittan received speaker fees, or research support or consulting fees from Janssen, Abbvie, Takeda, Neopharm and Pfizer. Nikolas Plevris received speaker fees and/or travel support from AbbVie, Takeda, Janssen, Norgine and Ferring. David Drobne has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen and Krka. Fabiana Castiglione received lecture fees from Abbvie, Takeda, Janssen, Sofar, Ferring. Richard James Harris received personal fees from Takeda, AbbVie and Janssen, and nonfinancial support from Falk. Yago Gonz?lez-Lama received consultancy, speaker fees and unrestricted grants from AbbVie, Janssen, Takeda, Pfizer, Ferring, Amgen, MSD. Shaji Sebastian holds research grants from Takeda, AbbVie, Warner Chilcott, Ferring, MSD, Biohit and Celgene, serves on the advisory boards of Janssen, Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene and Tillotts Pharma, and has received speaker fees from Abbvie, Jansen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar-Gil Shitrit- Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Waqqas Afif has been a speaker advisory board member, and or clinical investigator for Abbvie, Arena Pharmaceuticals, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Takeda, Janssen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar-Gil Shitrit- Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Stephan Vavricka received consultancy and speaker fees from Abbvie, Falk, Ferring, Janssen, MSD, Pfizer, Takeda, UCB, Vifor. Glen Doherty has received educational and research grants, and/or professional fees from Abbvie, MSD, Janssen, Takeda/Shire, Tillott's, Dr Falk, Mylan, Biogen, Celltrion and Amgen. Dr Charlie Lees has received research support from Abbvie and Gilead, acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, MSD, Hospira, Pharmacosmos, GSK, Gilead, Topivert, Vifor Pharma and Dr Falk and received speaking fees and travel support from Pfizer, Abbvie, MSD, Takeda, Shire, Ferring, Hospira, Warner-Chilcott and Dr Falk.Davide De Marco, Nicola Imperatore, Iria Baston-Rey, Marie Truyens, Viktor DomislovicVince Biemans, Sally Myers, Cyrielle Gilletta, Darragh Storan- did not have any conflict of interest to discloseAll authors approved the final version of the manuscriptNo funding was obtained for the study. No funding was obtained for the data analysis or writing of the paper. Funding Information: : Uri Kopylov received consultancy and speaker fees from Abbvie, Janssen, Takeda, MSD and Medtronic, and research grants from Janssen Takeda Medtronic. Jurij Hanzel received lecture fees from Biogen, Janssen and Takeda outside the submitted work. Claire Liefferinckx received consultancy fees from Takeda, and speaker fees from Sandoz, Janssen, Abbvie. Anneline Cremer received consultancy fees from Takeda and Janssen, and speaker fees from Pfizer and Abbvie. Denis Franchimont received educational grants from Abbvie, Takeda, MSD, fees or consultancy fees from Ferring, Falk, Chiesi, Abbvie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma and Hospira. Zeljko Krznaric received speaker fees from Abbvie, Takeda, MSD, Janssen, Oktal Pharma, Fresenius, Mylan and Pfizer. Manuel Barreiro‐de Acosta has served as a speaker, a consultant and advisory member for or received research funding from MSD, Abbvie, Celltrion, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Chiesi, Gebro Pharma, Roche, Otsuka Pharmaceuticals and Tillotts Pharma. Shomron Ben‐Horin received consulting and advisory board fees and research support from AbbVie, Janssen, Takeda and Celltrion, and consulting and speaker fees from Pfizer, GlaxoSmithKline and MSD. Frank Hoentjen has served on advisory boards or as speaker or consultant for Abbvie, Celgene, Janssen‐Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen‐Cilag, Abbvie. Klaudia Farkas received speaker fees from AbbVie, Takeda, Janssen and Ferring. Tam{\'a}s Moln{\'a}r received speaker fees from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer and Teva. Eran Zittan received speaker fees, or research support or consulting fees from Janssen, Abbvie, Takeda, Neopharm and Pfizer. Nikolas Plevris received speaker fees and/or travel support from AbbVie, Takeda, Janssen, Norgine and Ferring. David Drobne has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen and Krka. Fabiana Castiglione received lecture fees from Abbvie, Takeda, Janssen, Sofar, Ferring. Richard James Harris received personal fees from Takeda, AbbVie and Janssen, and nonfinancial support from Falk. Yago Gonz{\'a}lez‐Lama received consultancy, speaker fees and unrestricted grants from AbbVie, Janssen, Takeda, Pfizer, Ferring, Amgen, MSD. Shaji Sebastian holds research grants from Takeda, AbbVie, Warner Chilcott, Ferring, MSD, Biohit and Celgene, serves on the advisory boards of Janssen, Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene and Tillotts Pharma, and has received speaker fees from Abbvie, Jansen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar‐Gil Shitrit‐ Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Waqqas Afif has been a speaker advisory board member, and or clinical investigator for Abbvie, Arena Pharmaceuticals, Eli‐Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Takeda, Janssen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar‐Gil Shitrit‐ Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Stephan Vavricka received consultancy and speaker fees from Abbvie, Falk, Ferring, Janssen, MSD, Pfizer, Takeda, UCB, Vifor. Glen Doherty has received educational and research grants, and/or professional fees from Abbvie, MSD, Janssen, Takeda/Shire, Tillott's, Dr Falk, Mylan, Biogen, Celltrion and Amgen. Dr Charlie Lees has received research support from Abbvie and Gilead, acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, MSD, Hospira, Pharmacosmos, GSK, Gilead, Topivert, Vifor Pharma and Dr Falk and received speaking fees and travel support from Pfizer, Abbvie, MSD, Takeda, Shire, Ferring, Hospira, Warner‐Chilcott and Dr Falk.Davide De Marco, Nicola Imperatore, , Iria Baston‐Rey, Marie Truyens , Viktor DomislovicVince Biemans , Sally Myers, Cyrielle Gilletta, , Darragh Storan‐ did not have any conflict of interest to discloseAll authors approved the final version of the manuscriptNo funding was obtained for the study. No funding was obtained for the data analysis or writing of the paper. Declaration of personal interests Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons Ltd",

year = "2020",

month = jul,

day = "1",

doi = "10.1111/apt.15784",

language = "English",

volume = "52",

pages = "135--142",

journal = "Alimentary Pharmacology & Therapeutics",

issn = "0269-2813",

publisher = "Wiley",

number = "1",

}

Kopylov, U, Hanzel, J, Liefferinckx, C, De Marco, D, Imperatore, N, Plevris, N, Baston-Rey, I, Harris, RJ, Truyens, M, Domislovic, V, Vavricka, S, Biemans, V, Myers, S, Sebastian, S, Ben-Horin, S, Lama, YG, Gilletta, C, Ariella, BGS, Zelinkova, Z, Weishof, R, Storan, D, Zittan, E, Farkas, K, Molnar, T, Franchimont, D, Cremer, A, Afif, W, Castiglione, F, Lees, C, Barreiro-de Acosta, M, Lobaton, T, Doherty, G, Krznaric, Z, Pierik, M, Hoentjen, F & Drobne, D 2020, 'Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy', Alimentary Pharmacology & Therapeutics, vol. 52, no. 1, pp. 135-142. https://doi.org/10.1111/apt.15784

TY - JOUR

T1 - Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy

AU - Kopylov, U.

AU - Hanzel, J.

AU - Liefferinckx, C.

AU - De Marco, D.

AU - Imperatore, N.

AU - Plevris, N.

AU - Baston-Rey, I.

AU - Harris, R.J.

AU - Truyens, M.

AU - Domislovic, V.

AU - Vavricka, S.

AU - Biemans, V.

AU - Myers, S.

AU - Sebastian, S.

AU - Ben-Horin, S.

AU - Lama, Y.G.

AU - Gilletta, C.

AU - Ariella, B.G.S.

AU - Zelinkova, Z.

AU - Weishof, R.

AU - Storan, D.

AU - Zittan, E.

AU - Farkas, K.

AU - Molnar, T.

AU - Franchimont, D.

AU - Cremer, A.

AU - Afif, W.

AU - Castiglione, F.

AU - Lees, C.

AU - Barreiro-de Acosta, M.

AU - Lobaton, T.

AU - Doherty, G.

AU - Krznaric, Z.

AU - Pierik, M.

AU - Hoentjen, F.

AU - Drobne, D.

N1 - Funding Information: Uri Kopylov, designed the study, collected the data, performed the analysis and drafted the manuscriptJurij Hanzel, Claire Liefferinckx, Davide De Marco, Nicola Imperatore, Nikolas Plevris, Iria Baston-Rey, Richard J Harris, Marie Truyens, Viktor Domislovic, Stephan Vavricka, Vince Biemans, Sally Myers, Shaji Sebastian, Shomron Ben- Horin, Yago Gonz?lez Lama, Cyrielle Gilletta, Bar-Gil Shitrit Ariella, Zuzana Zelinkova, Roni Weishof, Darragh Storan, Eran Zittan, Klaudia Farkas, Tamas Molnar, Denis Franchimont, Anneline Cremer, Waqqas Afif, Fabiana Castiglione, Charles Lees, Manuel Barreiro-de Acosta, Triana Lobaton, Glen Doherty, Zeljko Krznaric, Marieke Pierik, Frank Hoentjen, David Drobne, collected the data, reviewed the manuscript and contributed valuable scientific content. Declaration of personal interests: Uri Kopylov received consultancy and speaker fees from Abbvie, Janssen, Takeda, MSD and Medtronic, and research grants from Janssen Takeda Medtronic. Jurij Hanzel received lecture fees from Biogen, Janssen and Takeda outside the submitted work. Claire Liefferinckx received consultancy fees from Takeda, and speaker fees from Sandoz, Janssen, Abbvie. Anneline Cremer received consultancy fees from Takeda and Janssen, and speaker fees from Pfizer and Abbvie. Denis Franchimont received educational grants from Abbvie, Takeda, MSD, fees or consultancy fees from Ferring, Falk, Chiesi, Abbvie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma and Hospira. Zeljko Krznaric received speaker fees from Abbvie, Takeda, MSD, Janssen, Oktal Pharma, Fresenius, Mylan and Pfizer. Manuel Barreiro-de Acosta has served as a speaker, a consultant and advisory member for or received research funding from MSD, Abbvie, Celltrion, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Chiesi, Gebro Pharma, Roche, Otsuka Pharmaceuticals and Tillotts Pharma. Shomron Ben-Horin received consulting and advisory board fees and research support from AbbVie, Janssen, Takeda and Celltrion, and consulting and speaker fees from Pfizer, GlaxoSmithKline and MSD. Frank Hoentjen has served on advisory boards or as speaker or consultant for Abbvie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen-Cilag, Abbvie. Klaudia Farkas received speaker fees from AbbVie, Takeda, Janssen and Ferring. Tam?s Moln?r received speaker fees from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer and Teva. Eran Zittan received speaker fees, or research support or consulting fees from Janssen, Abbvie, Takeda, Neopharm and Pfizer. Nikolas Plevris received speaker fees and/or travel support from AbbVie, Takeda, Janssen, Norgine and Ferring. David Drobne has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen and Krka. Fabiana Castiglione received lecture fees from Abbvie, Takeda, Janssen, Sofar, Ferring. Richard James Harris received personal fees from Takeda, AbbVie and Janssen, and nonfinancial support from Falk. Yago Gonz?lez-Lama received consultancy, speaker fees and unrestricted grants from AbbVie, Janssen, Takeda, Pfizer, Ferring, Amgen, MSD. Shaji Sebastian holds research grants from Takeda, AbbVie, Warner Chilcott, Ferring, MSD, Biohit and Celgene, serves on the advisory boards of Janssen, Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene and Tillotts Pharma, and has received speaker fees from Abbvie, Jansen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar-Gil Shitrit- Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Waqqas Afif has been a speaker advisory board member, and or clinical investigator for Abbvie, Arena Pharmaceuticals, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Takeda, Janssen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar-Gil Shitrit- Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Stephan Vavricka received consultancy and speaker fees from Abbvie, Falk, Ferring, Janssen, MSD, Pfizer, Takeda, UCB, Vifor. Glen Doherty has received educational and research grants, and/or professional fees from Abbvie, MSD, Janssen, Takeda/Shire, Tillott's, Dr Falk, Mylan, Biogen, Celltrion and Amgen. Dr Charlie Lees has received research support from Abbvie and Gilead, acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, MSD, Hospira, Pharmacosmos, GSK, Gilead, Topivert, Vifor Pharma and Dr Falk and received speaking fees and travel support from Pfizer, Abbvie, MSD, Takeda, Shire, Ferring, Hospira, Warner-Chilcott and Dr Falk.Davide De Marco, Nicola Imperatore, Iria Baston-Rey, Marie Truyens, Viktor DomislovicVince Biemans, Sally Myers, Cyrielle Gilletta, Darragh Storan- did not have any conflict of interest to discloseAll authors approved the final version of the manuscriptNo funding was obtained for the study. No funding was obtained for the data analysis or writing of the paper. Funding Information: : Uri Kopylov received consultancy and speaker fees from Abbvie, Janssen, Takeda, MSD and Medtronic, and research grants from Janssen Takeda Medtronic. Jurij Hanzel received lecture fees from Biogen, Janssen and Takeda outside the submitted work. Claire Liefferinckx received consultancy fees from Takeda, and speaker fees from Sandoz, Janssen, Abbvie. Anneline Cremer received consultancy fees from Takeda and Janssen, and speaker fees from Pfizer and Abbvie. Denis Franchimont received educational grants from Abbvie, Takeda, MSD, fees or consultancy fees from Ferring, Falk, Chiesi, Abbvie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma and Hospira. Zeljko Krznaric received speaker fees from Abbvie, Takeda, MSD, Janssen, Oktal Pharma, Fresenius, Mylan and Pfizer. Manuel Barreiro‐de Acosta has served as a speaker, a consultant and advisory member for or received research funding from MSD, Abbvie, Celltrion, Takeda, Janssen, Pfizer, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Chiesi, Gebro Pharma, Roche, Otsuka Pharmaceuticals and Tillotts Pharma. Shomron Ben‐Horin received consulting and advisory board fees and research support from AbbVie, Janssen, Takeda and Celltrion, and consulting and speaker fees from Pfizer, GlaxoSmithKline and MSD. Frank Hoentjen has served on advisory boards or as speaker or consultant for Abbvie, Celgene, Janssen‐Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen‐Cilag, Abbvie. Klaudia Farkas received speaker fees from AbbVie, Takeda, Janssen and Ferring. Tamás Molnár received speaker fees from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer and Teva. Eran Zittan received speaker fees, or research support or consulting fees from Janssen, Abbvie, Takeda, Neopharm and Pfizer. Nikolas Plevris received speaker fees and/or travel support from AbbVie, Takeda, Janssen, Norgine and Ferring. David Drobne has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen and Krka. Fabiana Castiglione received lecture fees from Abbvie, Takeda, Janssen, Sofar, Ferring. Richard James Harris received personal fees from Takeda, AbbVie and Janssen, and nonfinancial support from Falk. Yago González‐Lama received consultancy, speaker fees and unrestricted grants from AbbVie, Janssen, Takeda, Pfizer, Ferring, Amgen, MSD. Shaji Sebastian holds research grants from Takeda, AbbVie, Warner Chilcott, Ferring, MSD, Biohit and Celgene, serves on the advisory boards of Janssen, Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene and Tillotts Pharma, and has received speaker fees from Abbvie, Jansen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar‐Gil Shitrit‐ Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Waqqas Afif has been a speaker advisory board member, and or clinical investigator for Abbvie, Arena Pharmaceuticals, Eli‐Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Takeda, Janssen, Merck, Warner Chilcott and Falk Pharma. Ariella Bar‐Gil Shitrit‐ Grants; Takeda, Janssen. Lectures fee and advisory consultancy: Takeda, Janssen, Neopharm, Abbvie, Pfizer. Stephan Vavricka received consultancy and speaker fees from Abbvie, Falk, Ferring, Janssen, MSD, Pfizer, Takeda, UCB, Vifor. Glen Doherty has received educational and research grants, and/or professional fees from Abbvie, MSD, Janssen, Takeda/Shire, Tillott's, Dr Falk, Mylan, Biogen, Celltrion and Amgen. Dr Charlie Lees has received research support from Abbvie and Gilead, acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, MSD, Hospira, Pharmacosmos, GSK, Gilead, Topivert, Vifor Pharma and Dr Falk and received speaking fees and travel support from Pfizer, Abbvie, MSD, Takeda, Shire, Ferring, Hospira, Warner‐Chilcott and Dr Falk.Davide De Marco, Nicola Imperatore, , Iria Baston‐Rey, Marie Truyens , Viktor DomislovicVince Biemans , Sally Myers, Cyrielle Gilletta, , Darragh Storan‐ did not have any conflict of interest to discloseAll authors approved the final version of the manuscriptNo funding was obtained for the study. No funding was obtained for the data analysis or writing of the paper. Declaration of personal interests Publisher Copyright: © 2020 John Wiley & Sons Ltd

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited.Aim To assess the effectiveness of dose escalation of ustekinumab.Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

AB - Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited.Aim To assess the effectiveness of dose escalation of ustekinumab.Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

KW - experience

KW - induction

KW - EXPERIENCE

KW - INDUCTION

U2 - 10.1111/apt.15784

DO - 10.1111/apt.15784

M3 - Article

C2 - 32412134

SN - 0269-2813

VL - 52

SP - 135

EP - 142

JO - Alimentary Pharmacology & Therapeutics

JF - Alimentary Pharmacology & Therapeutics

IS - 1

ER -