Sub-optimal Response to Anti-Tumor Necrosis Factor's in Inflammatory Bowel Disease in Emerging Markets

Indicators of Sub-Optimal Response to Anti-Tumor Necrosis Factor (TNF) Therapy in Patients With Crohn's Disease (CD) and Ulcerative Colitis (UC): A Retrospective Chart Review in the Emerging Market (EM) Region (EXPLORE)

The purpose of this study is to establish the incidence of sub-optimal response to anti-TNF therapy in UC and CD participants.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative
• Intervention / Treatment: Drug: Anti-TNF Therapy

Detailed Description

Participants with historical diagnosis of CD and UC who were naïve to anti-TNF therapy were observed in this retrospective study. The study will look to identify the local barriers in prescribing anti-TNF therapy, treatment patterns and indicators of sub-optimal response to anti-TNF therapy in UC and CD participants in real-world clinical practice in the EM countries, along with the associated incidence of sub-optimal response and impact on health care resource utilization (HCRU). The will enroll approximately 2000 participants.

The study consists of two periods, eligibility period followed by a data abstraction period. During the eligibility period participants who had initiated first anti-TNF therapy during 01 March 2010 up to 01 March 2015 will be recruited and observed. Participants will be followed up for a period of minimum 2 years (other than death) and a maximum of 5 years from the date of first treatment of anti-TNF therapy for CD and UC (Index date). During the data abstraction period participants who have eligible medical charts will be identified and all retrospective data will be collected.

This multi-center trial will be conducted in Argentina, China, Colombia, Mexico, Russia, Saudi Arabia, Singapore, South Korea, Taiwan and Turkey. The overall time to abstract data during the data extraction period from the web-based electronic data capture (EDC) system will be approximately 1 year from March 2017 to February 2018.

• Study Type: Observational
• Enrollment (Actual): 1731

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1118AAT
    • Hospital Alemán
  • Ciudad Autonoma Buenos Aires, Argentina, C1280AEB
    • Hospital Britanico de Buenos Aires
  • Cordoba, Argentina, X5016KEH
    • Hospital Privado Centro Médico de Córdoba
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1181ACH
      • Hospital Italiano
    • La Plata, Buenos Aires, Argentina, B1900AXI
      • Hospital Italiano de la Plata
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-sen University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • The Affiliated Drum Tower Hospital of Nanjing University
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • First Affiliated Hospital of Dalian Medical University
  • Shanghai
    • Huangpu, Shanghai, China, 200020
      • Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200072
      • No. 10 People's Hospital of Shanghai
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The second affiliated hospital of zhejiang university school of medicine
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital affiliated with the Zhejiang University School of Medicine
• Colombia
  • Bogota, Colombia, 00000
    • Hospital Militar Central
  • Bogota, Colombia, 00000
    • Hospital Universitario San Ignacio
  • Ibague, Colombia, 730006
    • Institucion Mediservis Tolima IPS S.A.S
  • Medellin, Colombia, 050025
    • Instituto de Coloproctologia ICO S.A.S.
  • Medellin, Colombia, 050034
    • Hospital Pablo Tobón Uribe
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University
  • Gangwon-do
    • Wonju, Gangwon-do, Korea, Republic of, 26426
      • Yonsei University Wonju Severance Christian Hospital
  • Gyeonggi-do
    • Guri-si, Gyeonggi-do, Korea, Republic of, 11923
      • Hanyang University GURI Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic university of Korea, St. Vincent's Hospital
• Mexico
  • Distrito Federal, Mexico, 14050
    • Hospital Medica Sur
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 07020
      • Centro de Investigación Clinica Acelerada, S.C.
    • Mexico, Distrito Federal, Mexico, 14080
      • Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran
  • Estado De Mexico
    • Toluca de Lerdo, Estado De Mexico, Mexico, 50120
      • Centro de Investigacion y Manejo, Torre Medica Sanatorio Toluca
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37530
      • Investigacion Clinica de Leon S.C.
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64610
      • Centro Regiomontano de Estudios Clínicos Roma S.C.
• Russian Federation
  • Belgorod, Russian Federation, 308007
    • The Saint Ioasaf Belgorod Regional Hospital
  • Irkutsk, Russian Federation, 664047
    • Irkutsk State Regional Hospital
  • Kazan, Russian Federation, 420012
    • Kazan State Medical University
  • Moscow, Russian Federation, 111123
    • Moscow Clinical Research Center
  • Moscow, Russian Federation, 123423
    • FSBI State Scientific Centre of Coloproctology" of the MoH of RF
  • Moscow, Russian Federation, 129110
    • Moscow Region Research Cliniucal Institute
  • Saint Petersburg, Russian Federation, 197110
    • SBIH City Clinical Hospital #31
  • Saint-Petersburg, Russian Federation, 195067
    • Pokrovskaya Municipal Hospital
  • Saint-Petersburg, Russian Federation, 195220
    • Llc "Riat"
  • Stavropol, Russian Federation, 355017
    • FSBEI HE Stavropol State Medical University of Ministry of Healthcare of Russian Federation
• Saudi Arabia
  • Jeddah, Saudi Arabia, 21423
    • King Khalid National Guard Hospital
  • Jeddah, Saudi Arabia, 21533
    • King Fahd General Hospital
  • Khobar, Saudi Arabia, 31952
    • King Fahd University Hospital
  • Riyadh, Saudi Arabia, 11462
    • King Khalid University Hospital
  • Riyadh, Saudi Arabia, 14611
    • King Fahd Medical City
  • Riyadh, Saudi Arabia, 3354
    • King Faisal Specialist Hospital & Research Center
• Singapore
  • Singapore, Singapore, 119074
    • National University Cancer Institute,
  • Singapore, Singapore, 169608
    • Singapore General Hospital- Parent
  • Singapore, Singapore, 258499
    • CJ Ooi Gastroenterology Clinic Pte Ltd
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 529889
    • Changi General Hospital- Parent
• Taiwan
  • Changhua, Taiwan, 50004
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital, Linkou
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Medical Faculty
  • Ankara, Turkey, 06100
    • Turkiye Yuksek Ihtisas Training and Research Hospital
  • Ankara, Turkey, 06490
    • Baskent University Ankara Hospital
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical Faculty Sahinbey Educational Research Hospital
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34349
    • Acibadem Fulya Hospital
  • Istanbul, Turkey, 34668
    • Haydarpasa Numune Training and Research Hospital
  • Istanbul, Turkey, 34854
    • Istanbul Medeniyet Uni Goztepe Training&Res Hosp
  • Izmir, Turkey, 35965
    • Izmir Katip Celebi Univ. Ataturk Training and Research Hospital
  • Malatya, Turkey, 44280
    • Inonu Uni. Med. Fac.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of participants with a diagnosis of CD or UC who were naive to anti-TNF therapy and received their first dose of anti-TNF treatment for CD or UC during the eligibility period at private and public sites that routinely treat IBD participants and prescribe anti-TNF therapy from the targeted countries of interest.

Description

Inclusion Criteria:

1. Who are 18 years or older at Index Date and diagnosed with UC or CD.
2. Who were naive to anti-TNF therapy and received their first dose of any anti-TNF therapy (index date) for UC or CD within the Eligibility Period from 01 March 2010 through 01 March 2015.

Exclusion Criteria:

1. Diagnosed with indeterminate/unspecified type of IBD.
2. Were part of an IBD-related clinical trial during the observational period should be excluded (that is, index date up to the date of chart abstraction).
3. Who received an anti-TNF therapy for any non-UC or non-CD conditions (example, rheumatoid arthritis, ankylosing spondylitis, psoriasis, or cancer).
4. Who received an anti-TNF/biologic therapy at any point that was administered outside of the labelled dosing regimen (example, episodic use of anti-TNF therapy).
5. With UC who had a total colectomy prior to their first anti-TNF therapy.
6. Charts not available.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
All Participants; All participants with diagnosis of UC and CD, who initiated treatment with anti-TNF therapy from 01 March 2010 up to 01 March 2015 will be observed. Retrospective data extraction will be done for eligible participants from March 2017 up to approximately February 2018.	Drug: Anti-TNF Therapy; Anti-TNF therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Sub-optimal Response in UC and CD Participants	Incidence rate will be calculated as the number of events divided by the total person time at risk, for participants under anti-TNF therapy.	5 years
Treatment Patterns in UC and CD Participants		5 years
Number of Participants With Each Type of Anti-TNF Therapy		5 years
Duration of Treatment		5 years
Number of Participants With Response to Treatment	Number of participants with response to treatment will be assessed.	5 years
Treatment Pattern Results Stratified by Anti-TNF Response Group and by UC or CD Diagnosis	Treatment patterns results were as per the Anti-TNF therapy response from UC and CD participants.	5 years
Time-to-switch	The time to switch at which the participant switched to another anti-TNF therapy will be evaluated.	5 years
Time-to-first Indicator of Sub-optimal Therapy	Time-to-first indicator of sub-optimal therapy was defined as the occurrence of dose escalation, therapy augmentation, therapy switch, therapy discontinuation, hospitalization, or surgery of participant, which ever occurred first.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With CD Achieving Clinical Response Based on Harvey Bradshaw Index (HBI)	Clinical response is defined as a decrease in HBI score of greater than or equal to (>=) 3 points from baseline. HBI score is used to measure the disease activity of CD. It consists of clinical parameters: abdominal pain (0-3, higher score means more severe pain), number of liquid stools per day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score is the sum of individual parameters. The score ranges from a minimum score of 0 to no pre-specified maximum score as it depends on the number of liquid stools, where higher scores indicating more severe disease.	Baseline up to 5 years
Number of Participants With UC Achieving Clinical Response Based on Mayo Scores	Clinical response is defined as a decrease in the partial Mayo Score of at least 2 points and >=25% from baseline, with an accompanying decrease in rectal bleeding subscore of >=1 point from baseline or absolute rectal bleeding subscore of less than or equal to (<=) 1 point. Mayo score is an instrument designed to measure disease activity of UC. It consists of 3 subscores: stool frequency, rectal bleeding, and physician global assessment of disease severity, each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9; where higher scores indicating more severe disease.	Baseline up to 5 years
Number of Participants with Inflammatory Bowel Disease (IBD) Related Surgeries and Hospitalisation	IBD-related surgeries and hospitalisation will be conducted in the two years prior to index anti-TNF therapy in UC or CD participants.	2 years prior to index anti-TNF therapy
Number of Participants with Co-morbidities		Baseline
Number of Participants with Predictors of Sub-optimal Therapy in UC or CD Participants	The predictors of sub-optimal response will be assessed through multivariate analysis using logistic regression or other appropriate statistical methods. Multivariate analyses may be conducted to derive predictors of sub-optimal response to anti-TNF therapy globally and individually.	Baseline up to 5 years
Health Care Resources Utilisation (HCRU)	HCRU will be calculated for physician clinic visits, emergency department visits, IBD-related surgeries, invasive procedures, imaging, and in-participant admissions related to UC or CD, or related complications as available in the medical record and captured in the electronic case report form (eCRF).	Baseline up to 7 years
Physician Survey Questionnaire	The physician survey questionnaire will include questions on local accessibility to infusion centres, potential restrictions of prescription, potential local difficulties for drug access (example, reimbursement process, economic burden), and other reasons for participants compliant with the local label to not receive anti-TNF therapy.	Baseline

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Li J, Liu Z, Hu P, Wen Z, Cao Q, Zou X, Chen Y, Wang Y, Zhong J, Shen X, Demuth D, Fadeeva O, Xie L, Chen J, Qian J. Indicators of suboptimal response to anti-tumor necrosis factor therapy in patients from China with inflammatory bowel disease: results from the EXPLORE study. BMC Gastroenterol. 2022 Feb 4;22(1):44. doi: 10.1186/s12876-021-02074-z.
• Yamamoto-Furusho JK, Al Harbi O, Armuzzi A, Chan W, Ponce de Leon E, Qian J, Shapina M, Toruner M, Tu CH, Ye BD, Guennec M, Sison C, Demuth D, Fadeeva O, Khan QMR. Incidence of suboptimal response to tumor necrosis factor antagonist therapy in inflammatory bowel disease in newly industrialised countries: The EXPLORE study. Dig Liver Dis. 2020 Aug;52(8):869-877. doi: 10.1016/j.dld.2020.05.031. Epub 2020 Jun 17.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): June 13, 2018
• Study Completion (Actual): June 13, 2018

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 24, 2017

Study Record Updates

• Last Update Posted (Actual): June 26, 2018
• Last Update Submitted That Met QC Criteria: June 22, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Ulcer; Inflammatory Bowel Diseases; Crohn Disease; Necrosis; Intestinal Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IBD-5001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No