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

被引：61

作者：

Kopylov, Uri ^{[1
,2
,3
]}

Hanzel, Jurij ^{[4
]}

Liefferinckx, Claire ^{[5
]}

De Marco, Davide ^{[3
]}

Imperatore, Nicola ^{[6
]}

Plevris, Nikolas ^{[7
]}

Baston-Rey, Iria ^{[8
]}

Harris, Richard J. ^{[9
]}

Truyens, Marie ^{[10
]}

Domislovic, Viktor ^{[11
]}

Vavricka, Stephan ^{[12
]}

Biemans, Vince ^{[13
,14
]}

Myers, Sally ^{[15
]}

Sebastian, Shaji ^{[15
]}

Ben-Horin, Shomron ^{[1
,2
]}

Gonzalez Lama, Yago ^{[16
]}

Gilletta, Cyrielle ^{[17
]}

Ariella, Bar-Gil Shitrit ^{[18
]}

Zelinkova, Zuzana ^{[19
]}

Weishof, Roni ^{[20
,21
]}

Storan, Darragh ^{[22
,23
]}

Zittan, Eran ^{[24
]}

Farkas, Klaudia ^{[25
]}

Molnar, Tamas ^{[25
]}

Franchimont, Denis ^{[5
]}

Cremer, Anneline ^{[5
]}

Afif, Waqqas ^{[3
]}

Castiglione, Fabiana ^{[6
]}

Lees, Charles ^{[7
]}

Barreiro-de Acosta, Manuel ^{[8
]}

Lobaton, Triana ^{[10
]}

Doherty, Glen ^{[22
,23
]}

Krznaric, Zeljko ^{[20
,21
]}

Pierik, Marieke ^{[13
]}

Hoentjen, Frank ^{[14
]}

Drobne, David ^{[4
,26
]}

机构：

[1] Sheba Med Ctr, Dept Gastroenterol, Ramat Gan, Israel

[2] Tel Aviv Univ, Sackler Med Sch, Tel Aviv, Israel

[3] McGill Univ, Div Gastroenterol, Hlth Ctr, Montreal, PQ, Canada

[4] Univ Med Ctr Ljubljana, Dept Gastroenterol, Ljubljana, Slovenia

[5] ULB, Dept Gastroenterol, Hop Erasme, Brussels, Belgium

[6] Sch Med Federico II Naples, Dept Clin Med & Surg, Gastroenterol, Naples, Italy

[7] Western Gen Hosp, Edinburgh IBD Unit, Edinburgh, Midlothian, Scotland

[8] Hosp Clin Univ Santiago de Compostela, Serv Aparato Digest, Unidad EII, Santiago De Compostela, A Coruna, Spain

[9] Univ Hosp Southampton NHS Fdn Trust, Dept Gastroenterol, Southampton, Hants, England

[10] Ghent Univ Hosp, Dept Gastroenterol, Ghent, Belgium

[11] Univ Hosp Ctr Zagreb, Dept Gastroenterol & Hepatol, Zagreb, Croatia

[12] Ctr Gastroenterol & Hepatol, Zurich, Switzerland

[13] Maastricht Univ, Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Maastricht, Netherlands

[14] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands

[15] Hull Univ Teaching Hosp NHS Trust, IBD Unit, Kingston Upon Hull, N Humberside, England

[16] Hosp Univ Puerta de Hierro, Gastroenterol & Hepatol Dept, IBD Unit, Madrid, Spain

[17] CHU Toulouse Rangueil, Serv Gastroenterol & Nutr, Toulouse, France

[18] Hebrew Univ Jerusalem, Shaare Zedek Med Ctr, Med Sch, IBD MOM Unit,Digest Dis Inst, Jerusalem, Israel

[19] St Michaels Hosp, Dept Gastroenterol & Gastrointestinal Endoscopy, Bratislava, Slovakia

[20] Rambam Hlth Care Campus, Gastroenterol Dept, Haifa, Israel

[21] Technion Israel Inst Technol, Bruce Rappaport Sch Med, Haifa, Israel

[22] Univ Coll Dublin, St Vincents Univ Hosp, Ctr Colorectal Dis, Dublin, Ireland

[23] Univ Coll Dublin, Sch Med, Dublin, Ireland

[24] Emek Med Ctr Afula Israel, Ellen & Pinchas Mamber Inst Gastroenterol & Liver, IBD Unit, Afula, Israel

[25] Univ Szeged, Dept Med 1, Fac Med, Szeged, Hungary

[26] Univ Ljubljana, Med Fac, Ljubljana, Slovenia

来源：

ALIMENTARY PHARMACOLOGY & THERAPEUTICS | 2020年 / 52卷 / 01期

关键词：

INDUCTION; EXPERIENCE;

D O I：

10.1111/apt.15784

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：135 / 142

页数：8

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