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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03090139
• Collaborator: (none)
• Enrollment: 1,731
• Locations: 76
• Actual Duration (Months): 14.5
• Patients Per Site: 22.8
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases	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 Design

• Study Type: Observational
• Actual Enrollment: 1731 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: 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)
• Actual Study Start Date: Mar 28, 2017
• Actual Primary Completion Date: Jun 13, 2018
• Actual Study Completion Date: Jun 13, 2018

Arms and Interventions

Arm	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.

Outcome Measures

Primary Outcome Measures

1. Incidence Rate of Sub-optimal Response in UC and CD Participants [5 years]

   Incidence rate will be calculated as the number of events divided by the total person time at risk, for participants under anti-TNF therapy.

2. Treatment Patterns in UC and CD Participants [5 years]

3. Number of Participants With Each Type of Anti-TNF Therapy [5 years]

4. Duration of Treatment [5 years]

5. Number of Participants With Response to Treatment [5 years]

   Number of participants with response to treatment will be assessed.

6. Treatment Pattern Results Stratified by Anti-TNF Response Group and by UC or CD Diagnosis [5 years]

   Treatment patterns results were as per the Anti-TNF therapy response from UC and CD participants.

7. Time-to-switch [5 years]

   The time to switch at which the participant switched to another anti-TNF therapy will be evaluated.

8. Time-to-first Indicator of Sub-optimal Therapy [5 years]

   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.

Secondary Outcome Measures

1. Number of Participants With CD Achieving Clinical Response Based on Harvey Bradshaw Index (HBI) [Baseline up to 5 years]

   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.

2. Number of Participants With UC Achieving Clinical Response Based on Mayo Scores [Baseline up to 5 years]

   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.

3. Number of Participants with Inflammatory Bowel Disease (IBD) Related Surgeries and Hospitalisation [2 years prior to index anti-TNF therapy]

   IBD-related surgeries and hospitalisation will be conducted in the two years prior to index anti-TNF therapy in UC or CD participants.

4. Number of Participants with Co-morbidities [Baseline]

5. Number of Participants with Predictors of Sub-optimal Therapy in UC or CD Participants [Baseline up to 5 years]

   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.

6. Health Care Resources Utilisation (HCRU) [Baseline up to 7 years]

   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).

7. Physician Survey Questionnaire [Baseline]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Italiano	Ciudad Autonoma Buenos Aires	Buenos Aires	Argentina	C1181ACH
2	Hospital Italiano de La Plata	La Plata	Buenos Aires	Argentina	B1900AXI
3	Hospital Aleman	Ciudad Autonoma Buenos Aires		Argentina	C1118AAT
4	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires		Argentina	C1280AEB
5	Hospital Privado Centro Medico de Cordoba	Cordoba		Argentina	X5016KEH
6	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
7	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510655
8	The Affiliated Drum Tower Hospital of Nanjing University	Nanjing	Jiangsu	China	210008
9	First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning	China	116011
10	Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.	Huangpu	Shanghai	China	200020
11	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
12	No. 10 People's Hospital of Shanghai	Shanghai	Shanghai	China	200072
13	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
14	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
15	Sir Run Run Shaw Hospital affiliated with the Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310016
16	Hospital Militar Central	Bogota		Colombia	00000
17	Hospital Universitario San Ignacio	Bogota		Colombia	00000
18	Institucion Mediservis Tolima IPS S.A.S	Ibague		Colombia	730006
19	Instituto de Coloproctologia ICO S.A.S.	Medellin		Colombia	050025
20	Hospital Pablo Tobon Uribe	Medellin		Colombia	050034
21	Yonsei University Wonju Severance Christian Hospital	Wonju	Gangwon-do	Korea, Republic of	26426
22	Hanyang University Guri Hospital	Guri-si	Gyeonggi-do	Korea, Republic of	11923
23	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
24	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
25	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
26	Seoul National University Hospital	Seoul		Korea, Republic of	03080
27	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
28	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
29	Asan Medical Center	Seoul		Korea, Republic of	05505
30	Samsung Medical Center	Seoul		Korea, Republic of	06351
31	Centro de Investigacion Clinica Acelerada, S.C.	Mexico	Distrito Federal	Mexico	07020
32	Instituto Nacional de Ciencias Medicas y Nutricion Dr. Salvador Zubiran	Mexico	Distrito Federal	Mexico	14080
33	Centro de Investigacion y Manejo, Torre Medica Sanatorio Toluca	Toluca de Lerdo	Estado De Mexico	Mexico	50120
34	Investigacion Clinica de Leon S.C.	Leon	Guanajuato	Mexico	37530
35	Centro Regiomontano de Estudios Clinicos Roma S.C.	Monterrey	Nuevo Leon	Mexico	64610
36	Hospital Medica Sur	Distrito Federal		Mexico	14050
37	The Saint Ioasaf Belgorod Regional Hospital	Belgorod		Russian Federation	308007
38	Irkutsk State Regional Hospital	Irkutsk		Russian Federation	664047
39	Kazan State Medical University	Kazan		Russian Federation	420012
40	Moscow Clinical Research Center	Moscow		Russian Federation	111123
41	FSBI State Scientific Centre of Coloproctology" of the MoH of RF	Moscow		Russian Federation	123423
42	Moscow Region Research Cliniucal Institute	Moscow		Russian Federation	129110
43	SBIH City Clinical Hospital #31	Saint Petersburg		Russian Federation	197110
44	Pokrovskaya Municipal Hospital	Saint-Petersburg		Russian Federation	195067
45	Llc "Riat"	Saint-Petersburg		Russian Federation	195220
46	FSBEI HE Stavropol State Medical University of Ministry of Healthcare of Russian Federation	Stavropol		Russian Federation	355017
47	King Khalid National Guard Hospital	Jeddah		Saudi Arabia	21423
48	King Fahd General Hospital	Jeddah		Saudi Arabia	21533
49	King Fahd University Hospital	Khobar		Saudi Arabia	31952
50	King Khalid University Hospital	Riyadh		Saudi Arabia	11462
51	King Fahd Medical City	Riyadh		Saudi Arabia	14611
52	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia	3354
53	National University Cancer Institute,	Singapore		Singapore	119074
54	Singapore General Hospital- Parent	Singapore		Singapore	169608
55	CJ Ooi Gastroenterology Clinic Pte Ltd	Singapore		Singapore	258499
56	Tan Tock Seng Hospital	Singapore		Singapore	308433
57	Changi General Hospital- Parent	Singapore		Singapore	529889
58	Changhua Christian Hospital	Changhua		Taiwan	50004
59	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
60	Chung Shan Medical University Hospital	Taichung		Taiwan	402
61	China Medical University Hospital	Taichung		Taiwan	40447
62	National Cheng Kung University Hospital	Tainan		Taiwan	704
63	National Taiwan University Hospital	Taipei		Taiwan	100
64	Mackay Memorial Hospital	Taipei		Taiwan	10449
65	Chang Gung Memorial Hospital, Linkou	Taoyuan		Taiwan	333
66	Ankara University Medical Faculty	Ankara		Turkey	06100
67	Turkiye Yuksek Ihtisas Training and Research Hospital	Ankara		Turkey	06100
68	Baskent University Ankara Hospital	Ankara		Turkey	06490
69	Gazi University Medical Faculty	Ankara		Turkey	06500
70	Gaziantep University Medical Faculty Sahinbey Educational Research Hospital	Gaziantep		Turkey	27310
71	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
72	Acibadem Fulya Hospital	Istanbul		Turkey	34349
73	Haydarpasa Numune Training and Research Hospital	Istanbul		Turkey	34668
74	Istanbul Medeniyet Uni Goztepe Training&Res Hosp	Istanbul		Turkey	34854
75	Izmir Katip Celebi Univ. Ataturk Training and Research Hospital	Izmir		Turkey	35965
76	Inonu Uni. Med. Fac.	Malatya		Turkey	44280

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03090139
• Other Study ID Numbers: IBD-5001
• First Posted: Mar 24, 2017
• Last Update Posted: Jun 26, 2018
• Last Verified: Jun 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Crohn Disease; Colitis; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis, Ulcerative; Ulcer; Necrosis

Study Results

No Results Posted as of Jun 26, 2018