Post-Marketing Use Of CT-P13 (Infliximab) For Standard Of Care Treatment Of Inflammatory Bowel Disease

Study Overview
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Brief Summary
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This is a post-marketing observational study of patients with Inflammatory Bowel Disease (specifically, Crohn's disease or Ulcerative Colitis) who have been prescribed CT-P13 (infliximab) or Remicade (infliximab) for treatment. CT-P13 (brand names Inflectra and Remsima) is a biosimilar medicine to Remicade, meaning it is a biologic medicine that contains the same active substance as Remicade (infliximab). The key study objectives are as follows: To characterize the population and drug utilization patterns of patients treated with CT-P13 for Crohn's Disease (CD) or Ulcerative Colitis (UC) in the context of standard of care Remicade To explore the long-term safety profile of CT-P13 in the treatment of patients with CD or UC in the context of standard of care Remicade To assess the effectiveness of CT-P13 in the treatment of patients with CD or UC in the context of standard of care Remicade

Detailed Description
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The study will be conducted in accordance with legal and regulatory requirements with scientific purpose, value and rigor following generally accepted research practices described in Guidelines for Good Pharmacoepidemiology Practices (GPP), Good Epidemiological Practice (GEP), Good Practices for Outcomes Research, International Ethical Guidelines for Epidemiological Research, European Medicines Agency (EMA) European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on Methodological Standards in Pharmacoepidemiology, and FDA Guidance for Industry. Data sources will be validated and will consist of the hospital medical records and monitoring will be organized on a regular basis. Data for the study will be entered into a web based electronic data capture (EDC) system at enrolment and then approximately every 3 months (at a minimum) thereafter up to 2 years. Adverse events will be encoded according to MedDRA 17.1 or later. The sample size will be approximately 2500 patients recruited over a 30 month period and followed up to 2 years. No inferential analyses are planned. Statistical analysis will be descriptive in nature.

Official Title
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POST-MARKETING OBSERVATIONAL COHORT STUDY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD) TREATED WITH CT-P13 IN USUAL CLINICAL PRACTICE (CONNECT-IBD)

Conditions
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Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: CT-P13
* Drug: Remicade


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 12 years of age at the time of initial confirmed diagnosis of CD or UC and at least 18 years of age at the time of enrolment to the study. Patients who are prescribed CT-P13 or Remicade for the treatment of CD or UC prescribed according to the corresponding summary of product characteristics (SmPC) as determined by the Investigator. Patients with stomas or surgery/pouch will be included. Exclusion Criteria: Any reported contraindications for CT-P13 or Remicade, according to the SmPC. Known hypersensitivity (including severe, acute infusion reactions) to infliximab, its excipients or other murine proteins, at the time of enrolment. Prior history of failure to respond to Remicade or CT-P13.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CT-P13<br>biosimilar infliximab | Drug: CT-P13<br>* biosimilar infliximab<br>* Other names: Remsima;|
| Remicade<br>infliximab | Drug: Remicade<br>* infliximab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Characteristics of Participants: Disease Duration | Disease duration was defined as the number of months from initial diagnosis of inflammatory bowel disease (CD or UC) to the date of informed consent, which was recorded at the time of enrollment into the study (baseline). | Baseline (Day 1) | 
| Number of Participants Who Switched Treatment | Here, number of participants with either UC or CD, who switched from remicade to CT-P13; switched from CT-P13 to remicade and multiple switchers were reported. | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Reasons for Switching Treatment by Participants |  | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Total Dose of Infusion Received | Total dose of infusion received by the participants was calculated. | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Number of Participants by Frequency of Infusion Received | Number of participants by infusion frequency (weeks) were reported at baseline and categorized as follows: once a week; once every 2 weeks; once every 3 weeks; once every 4 weeks; once every 5 weeks; once every 6 weeks; once every 7 weeks; once every 8 weeks and others. Here, 'Others' category included all the frequencies apart from the mentioned categories. | Baseline (Day 1) | 
| Number of Participants Who Had Change in Infusion Dose | Participants who had change in the dose of infusion (either dose reduction or increase in dose) were included and reported. | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Number of Participants Who Had Change in Infusion Dose Categorized Based on Reasons of Change | Participants who had change in infusion dose due to various reasons such as principal investigator's decision, participant's decisions, loss of response, lack of compliance, hypersensitivity, occurrence of adverse event (including adverse event special interest [AESI]/ serious adverse event [SAE]), positive for antibodies and other were reported. Here, 'Others' category included all reasons apart from the mentioned categories. A participant could have different reasons of dose change across visits, hence could be counted in more than one category. | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Number of Participants Who Took Concomitant Medications Related to the Treatment of Crohn's Disease (CD) or Ulcerative Colitis (UC) |  | From baseline to follow-up period (up to a maximum duration of 2 years) | 
| Number of Participants With Treatment-Emergent Adverse Event (AEs), Serious Adverse Events (SAEs) and Adverse Event With Special Interest (AESIs) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent were events between first dose of infusion up to month 24, that were absent before treatment or that worsened relative to pretreatment state. Hypersensitivity was the pre-defined TEAE of special Interest for this study. AEs included both serious and non-serious adverse events. | From baseline to follow-up period (up to a maximum duration of 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Remaining in Clinical Remission or Relapse | Clinical remission in participants was defined by a total Mayo score of 2 points or lower, with no individual sub score exceeding 1 point. Mayo score is an instrument designed to measure disease activity. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of centrally read flexible proctosigmoidoscopy and physician's global assessment, each sub score graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher scores indicating more severe disease. The relapse of clinical remission was defined as the time from the date of first attaining CR to the date of relapse or death from any cause, whichever occurred first. | Months 6, 12, 18 and 24 | 
| Crohn's Disease: Number of Participants With Shift From Baseline in Harvey Bradshaw Index (HBI) According to Clinical Remission | HBI is a simple index of CD activity. HBI measures 5 parameters; the general well-being (ranging from 0=very well to 4=terrible), abdominal pain ranging from 0 (none) to 3 (severe), number of liquid stools per day (no maximum score), presence of an abdominal mass on physical exam ranging from 0 (none) to 3 (definite and tender), and whether there are any complications ranging from 0=no complications, 1=Arthralgia; 2=Uveitis; 3=Erythema nodosum; 4=Aphthous ulcer; 5=Pyoderma gangrenosum; 6=Anal fissure; 7=New fistula and 8=abscess). The total HBI score is the sum of all the 5 individual parameters, the minimum score is 0 and there was no pre-specified maximum score as it depends on the number of liquids stools. Higher HBI scores=greater disease activity. The level of disease activity was interpreted as clinical remission (CR) (score less than [<] 5), mild disease (MD) (score equal to [=] 5 to 7), moderate disease (Mod D) (score=8 to 16) and severe disease (SD) (score more than [>] 16). | Baseline, Months 6, 12, 18 and 24 | 
| Crohn's Disease: Number of Participants With Shift From Baseline in Harvey Bradshaw Index According to Disease Activity | HBI is a simple index of CD activity. HBI measures 5 clinical parameters; the general well-being ranging from 0 (very well) to 4 (terrible), abdominal pain ranging from 0 (none) to 3 (severe), number of liquid stools per day (no maximum score), presence of an abdominal mass on physical exam ranging from 0 (none) to 3 (definite and tender), and whether there are any complications ranging from 0=no complications, 1=Arthralgia; 2=Uveitis; 3=Erythema nodosum; 4=Aphthous ulcer; 5=Pyoderma gangrenosum; 6=Anal fissure; 7=New fistula and 8=abscess). The total HBI score is the sum of all the 5 individual parameters, the minimum score is 0 and there was no pre-specified maximum score as it depends on the number of liquids stools. Higher HBI scores=greater disease activity. The level of disease activity was interpreted as clinical remission (CR) (HBI score < 5), mild disease (MD) (HBI score = 5 to 7), moderate disease (Mod D) (HBI score = 8 to 16) and severe disease (SD) (HBI score >16). | Baseline, Months 6, 12, 18 and 24 | 
| Ulcerative Colitis: Number of Participants With Shift From Baseline in Partial Mayo Scoring System According to Clinical Remission | Mayo Score is an instrument to measure disease activity of UC. Score ranges from 0 to 12 points. It consists of 4 sub scores, each graded from 0 to 3. Higher scores = more severe disease. A Partial Mayo Score (PMS) (Mayo score without endoscopy) is comprised of 3 parameters: stool frequency ranging from 0 (normal number of stools) to 3 (having >=5 stools more than normal), the presence of rectal bleeding (ranging from 0=no blood seen to 3=blood alone passes), and physician's global assessment (ranging from 0=normal to 3=severe disease). The total partial Mayo score was the sum of all the parameters, score ranging from 0 (normal or inactive disease) to 9 (severe disease). Higher scores indicated more severe disease. The score was calculated if data were available for at least 1 of 3 Mayo sub scores. The level of disease activity was interpreted as clinical remission (CR) (PMS <2), mild disease (MD) (PMS=2 to 4), moderate disease (Mod D) (PMS=5 to 6) and severe disease (SD) (PMS >6). | Baseline, Months 6, 12, 18 and 24 | 
| Ulcerative Colitis: Number of Participants With Shift From Baseline in Partial Mayo Scoring System According to Disease Activity | Mayo Score is an instrument to measure disease activity of UC. Score ranges from 0 to 12 points. It consists of 4 sub scores, each graded from 0 to 3. Higher scores= more severe disease. A Partial Mayo Score (PMS) (Mayo score without endoscopy) is comprised of 3 parameters: stool frequency ranging from 0 (normal number of stools) to 3 (having >=5 stools more than normal), the presence of rectal bleeding ranging from 0 (no blood seen) to 3 (blood alone passes), and physician's global assessment ranging from 0 (normal) to 3 (severe disease). The total partial Mayo score was the sum of all the parameters, score ranging from 0 (normal or inactive disease) to 9 (severe disease). Higher scores indicated more severe disease. The score was calculated if data were available for at least 1 of 3 Mayo sub scores. The level of disease activity was interpreted as clinical remission (CR) (PMS <2), mild disease (MD) (PMS=2 to 4), moderate disease (Mod D) (PMS=5 to 6) and severe disease (SD) (PMS >6). | Baseline, Months 6, 12, 18 and 24 | 
| Crohn's Disease: Number of Participants Categorized on the Basis of Montreal Classification Index by Age at Diagnosis | The Montreal classification index for CD was used to classify the extent of the disease activity. It consisted of three parameters: age at diagnosis, location and behavior of the disease activity. There were four different age groups categorized: 16 years or younger, 17-40 years, over 40 years and missing. | At Baseline | 
| Crohn's Disease: Number of Participants Categorized on the Basis of Montreal Classification Index by Location | The Montreal classification index for CD was used to classify the extent of the disease activity. It consisted of three parameters: age at diagnosis, location and behavior of the disease activity. There are four different disease locations presented: Location 1 (L1) is terminal ileum, Location 2 (L2) is colon, Location 3 (L3) is ileocolon and Location 4 (L4) is upper gastrointestinal (GI). The first three categories (L1-L3) was combined with L4 where disease sites coexisted. | Baseline, Months 6, 12, 18 and 24 | 
| Crohn's Disease: Number of Participants Categorized on the Basis of Montreal Classification Index by Behavior of the Disease Activity | The Montreal classification index for CD was used to classify the extent of the disease activity. It consists of two parameters: location and behavior of the disease activity. There were 4 different categories for the behavior of the disease activity: Behaviour 1 (B1) was nonstricturing (NS), nonpenetrating (NP); Behaviour 2 (B2) was structuring; Behaviour 3 (B3) was penetrating and p as perianal disease (p). The first 3 categories (B1 to B3) could be added with p to indicate coexisting perianal disease. Perianal disease (p) was defined as the presence of perianal abscesses or fistulae. | Baseline, Months 6, 12, 18 and 24 | 
| Ulcerative Colitis: Number of Participants Categorized on the Basis of Montreal Classification Index by Extent | The Montreal classification index for Ulcerative Colitis (UC) was used to classify the extent and severity of the disease activity. There were three subgroups of UC defined by extent: Extent 1 (E1) =Ulcerative proctitis, Extent 2 (E2) =Left-sided UC and Extent 3 (E3) =Extensive UC. | Baseline, Months 6, 12, 18 and 24 | 
| Ulcerative Colitis: Number of Participants Categorized on the Basis of Montreal Classification Index by Severity | The Montreal classification index for UC was used to classify the extent and severity of the disease activity. UC can be classified broadly into four disease activity/severity categories: Severity 0 (S0) = asymptomatic clinical remission; Severity 1 (S1) = Mild UC (passage of four or fewer stools/day [with or without blood], absence of any systemic illness, and normal inflammatory markers); Severity 2 (S2) = Moderate UC (passage of more than four stools per day but with minimal signs of systemic toxicity) and Severity 3 (S3) = Severe UC (passage of at least six bloody stools daily). | Baseline, Months 6, 12, 18 and 24 | 
| Crohn's Disease: Number of Participants Categorized on the Basis of Fistula Drainage Assessment Index | The fistula drainage assessment index was used to assess the improvement or remission of the disease activity of Crohn's Disease, based on 6 categories: remission (remission was defined as closure of all fistulae that were draining at baseline for at least two consecutive visits); improvement (improvement defined as a decrease from baseline in the number of open draining fistulae of 50% for at least two consecutive visits); worsened; unchanged; not accessible and missing disease activity. | Baseline, Months 6, 12, 18 and 24 | 
| Mean Change From Baseline in Laboratory Test Results: C-Reactive Protein at Months 6, 12, 18, and 24 | C-reactive protein (CRP) was a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra-sensitive assay. A decrease in the level of CRP indicated reduction in inflammation and therefore improvement. | Baseline, Months 6, 12, 18 and 24 | 
| Mean Change From Baseline in Laboratory Test Results: Fecal Calprotectin at Months 6, 12, 18, and 24 | Here, the laboratory tests related to the treatment or assessment of Crohn's Disease or Ulcerative Colitis was fecal calprotectin. | Baseline, Months 6, 12, 18, and 24 | 
| Number of Participants With Imaging Test Results | Number of participants who had Imaging test results related to the treatment or assessment of Crohn's Disease or Ulcerative Colitis were reported. | From baseline up to follow-up period (a maximum of 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CT-P13, Inflectra, Remicade, Infliximab, Observational, Follow-up, Safety, Effectiveness