Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis A Randomized Clinical Trial

被引:47
|
作者
Zhang, Shenghong [1 ]
Chen, Baili [1 ]
Wang, Bangmao [2 ]
Chen, Hong [3 ]
Li, Yan [4 ]
Cao, Qian [5 ]
Zhong, Jie [6 ]
Shieh, Ming-Jium [7 ]
Ran, Zhihua [8 ]
Tang, Tongyu [9 ]
Yang, Ming [10 ]
Xu, Beibei [10 ]
Wang, Qiang [10 ]
Liu, Yunjie [10 ]
Ma, Lijia [10 ]
Wang, Xiaolin [11 ]
Zhang, Nan [11 ]
Zhang, Su [11 ]
Guo, Wenyu [11 ]
Huang, Liang [11 ]
Schreiber, Stefan [12 ]
Chen, Minhu [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou, Peoples R China
[2] Tianjin Med Univ, Gen Hosp, Dept Gastroenterol & Hepatol, Tianjin, Peoples R China
[3] Southeast Univ, Affiliated ZhongDa Hosp, Dept Gastroenterol, Sch Med, Nanjing, Peoples R China
[4] China Med Univ, Dept Gastroenterol, Shengjing Hosp, Shenyang, Peoples R China
[5] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gastroenterol, Hangzhou, Peoples R China
[6] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China
[7] Natl Taiwan Univ Hosp & Coll Med, Dept Oncol, Taipei, Taiwan
[8] Shanghai Jiao Tong Univ, Renji Hosp, Div Gastroenterol & Hepatol, Sch Med, Shanghai, Peoples R China
[9] Jilin Univ, Bethune Affiliated Hosp 1, Dept Gastroenterol, Changchun, Peoples R China
[10] I Mab Biopharm Shanghai, Shanghai, Peoples R China
[11] I Mab Biopharm Hangzhou, Hangzhou, Peoples R China
[12] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Med 1, Kiel, Germany
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2023年 / 329卷 / 09期
关键词
INFLAMMATORY-BOWEL-DISEASE; MAINTENANCE THERAPY; INTERLEUKIN-6; TOFACITINIB; RECEPTOR; ASIA;
D O I
10.1001/jama.2023.1084
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IMPORTANCE Olamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression. OBJECTIVE To assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis.DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score =5, rectal bleeding score =1, endoscopy score =2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020.INTERVENTIONS Eligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks. MAIN OUTCOMES AND MEASURES The primary end point was clinical response at week 12 (defined as =3 and =30% decrease from baseline total Mayo score; range, 0-12 [worst] with =1 decrease and =1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12.RESULTS Ninety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, -12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo.CONCLUSIONS AND RELEVANCE Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety.
引用
收藏
页码:725 / 734
页数:10
相关论文
共 50 条
  • [31] Review article: induction therapy for patients with active ulcerative colitis
    Travis, S. P. L.
    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2006, 24 : 10 - 16
  • [32] Clinical Predictors of Response to Faecal Microbiota Transplantation in Patients with Active Ulcerative Colitis
    Sood, Ajit
    Singh, Arshdeep
    Mahajan, Ramit
    Midha, Vandana
    Kaur, Kirandeep
    Singh, Dharmatma
    Bansal, Namita
    Dharni, Khushdeep
    JOURNAL OF CROHNS & COLITIS, 2021, 15 (02): : 238 - 243
  • [33] Corticosteroid therapy in ulcerative colitis: Clinical response and predictors
    Li, Jin
    Wang, Fan
    Zhang, Hong-Jie
    Sheng, Jian-Qiu
    Yan, Wen-Feng
    Ma, Min-Xing
    Fan, Ru-Ying
    Gu, Fang
    Li, Chuan-Feng
    Chen, Da-Fan
    Zheng, Ping
    Gu, Yu-Pei
    Cao, Qian
    Yang, Hong
    Qian, Jia-Ming
    Hu, Pin-Jin
    Xia, Bing
    WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (10) : 3005 - 3012
  • [34] Corticosteroid therapy in ulcerative colitis:Clinical response and predictors
    Jin Li
    Fan Wang
    Hong-Jie Zhang
    Jian-Qiu Sheng
    Wen-Feng Yan
    Min-Xing Ma
    Ru-Ying Fan
    Fang Gu
    Chuan-Feng Li
    Da-Fan Chen
    Ping Zheng
    Yu-Pei Gu
    Qian Cao
    Hong Yang
    Jia-Ming Qian
    Pin-Jin Hu
    Bing Xia
    World Journal of Gastroenterology, 2015, (10) : 3005 - 3012
  • [35] Efficacy of Plantago major seed in management of ulcerative colitis symptoms: A randomized, placebo controlled, clinical trial
    Baghizadeh, Atiyeh
    Davati, Ali
    Heidarloo, Ali Jafari
    Emadi, Fatemeh
    Aliasl, Jale
    COMPLEMENTARY THERAPIES IN CLINICAL PRACTICE, 2021, 44
  • [36] Trichuris suis therapy for active ulcerative colitis:: A randomized controlled trial
    Summers, RW
    Elliott, DE
    Urban, JF
    Thompson, RA
    Weinstock, JV
    GASTROENTEROLOGY, 2005, 128 (04) : 825 - 832
  • [37] EFFECT OF OCTAGAM 10% IVIG VERSUS PLACEBO ON CLINICAL RESPONSE IN PATIENTS WITH DERMATOMYOSITIS: THE PRODERM RANDOMIZED CLINICAL TRIAL
    Aggarwal, Rohit
    Charles-Schoeman, Christina
    Schessl, Joachim
    Bata-Csorgo, Zsuzsanna
    Dimachkie, Mazen
    Griger, Zoltan
    Moiseev, Sergey
    Schiopu, Elena
    Vencovsky, Jiri
    Beckmann, Irene
    Clodi, Elisabeth
    Levine, Todd
    MUSCLE & NERVE, 2020, 62 : S83 - S84
  • [38] Clinical Response and Complications are not Associated with Drug Levels in Patients with Severe Ulcerative Colitis on IV Cyclosporine Induction Therapy
    Patel, Parita
    Yarur, Andres
    Dalal, Sushila
    Sakuraba, Atsuhi
    Rubin, David T.
    Hanauer, Stephen B.
    Hanan, Ira
    Raffals, Laura H.
    Cohen, Russell D.
    Pekow, Joel
    INFLAMMATORY BOWEL DISEASES, 2018, 24 (06) : 1291 - 1297
  • [39] Impact of an intervention program on drug adherence in patients with ulcerative colitis: Randomized clinical trial
    Pacheco, Mila
    Sa, Pedro
    Santos, Glaucia
    Boa-Sorte, Ney
    Domingues, Kilma
    Assis, Larissa
    Silva, Marina
    Oliveira, Ana
    Santos, Daniel
    Ferreira, Jamile
    Fernandes, Rosemeire
    Fortes, Flora
    Rocha, Raquel
    Santana, Genoile
    PLOS ONE, 2023, 18 (12):
  • [40] The effects of probiotics in ulcerative colitis patients: a randomized controlled double blind clinical trial
    Tamizifar, Babak
    Feizi, Awat
    Khorasani, Marzieh Rahim
    Kassaian, Nazila
    Zamanimoghadam, Ali
    Arbabnia, Shayan
    Sede, Peyman Adibi
    FUNCTIONAL FOODS IN HEALTH AND DISEASE, 2023, 13 (11): : 605 - 615