Post-Marketing Use Of CT-P13 (Infliximab) For Standard Of Care Treatment Of Rheumatoid Diseases Who Are Naïve To Biologics Or Switched From Remicade

Study Overview
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Brief Summary
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To assess persistence of CT-P13 in patients with Rheumatoid Diseases (Rheumatoid arthritis [RA], ankylosing spondylitis [AS], and psoriatic arthritis [PsA]) who are naïve to biologics or are switching from stable Remicade to CT-P13. The main objectives of the study are: To evaluate real-life drug persistence in RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade To characterise the patient populations and drug usage patterns of RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade To assess the safety of CT-P13 in RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade for up to 2 years

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 sources will be validated. The source data will consist of medical records, physician questionnaires, and patient questionnaires. Data for the study will be entered into an electronic data capture system. Questionnaires will be completed on electronic tablets. The study is a one year enrollment period with a two year follow-up period. The study plans to enroll patients throughout Canada and Europe.

Official Title
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PERSIST: PROSPECTIVE OBSERVATIONAL COHORT STUDY TO ASSESS PERSISTENCE OF CT-P13 (INFLIXIMAB) IN PATIENTS WITH RHEUMATOID DISEASES WHO ARE EITHER NAIVE TO BIOLOGICS OR SWITCHED FROM STABLE REMICADE(R) (INFLIXIMAB)

Conditions
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Rheumatoid Diseases, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis

Intervention / Treatment
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* Drug: CT-P13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18 years old at the time of enrollment Patients who are prescribed CT-P13 or Remicade for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis prescribed according to the corresponding summary of product characteristics (SmPC and Product Monograph) as determined by the investigator Exclusion Criteria: Any reported contraindications for Inflectra according to the SmPC or Product Monograph Known hypersensitivity (including severe, acute infusion reactions) to infliximab, its excipients or other murine proteins, at the time of enrollment

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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Persistence With CT-P13 in Participants With Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) | Persistence (in days) was defined as a continuous variable measured in time from index date until date of drug discontinuation. Drug discontinuation was defined as either switching to another non infliximab BDMARD or elapsing of a drug free interval of 16 weeks from CT-P13. For participants undergoing a switch to CT-P13 from Remicade, the index date was considered the date from which Remicade was originally commenced and for participants who initiated treatment with CT-P13 as their first biologic, the index date was considered the date from which CT-P13 was initiated. | During the observation period of 2 years | 
| Disease Duration in Participants With Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA), as Recorded on the Day of Inclusion in Study | Disease duration was defined as the number of months from initial diagnosis of rheumatoid disease (RA, AS or PsA) to the date of informed consent, which was recorded at the time of inclusion in the study (Day 1). | At Day 1 of 2 year observation period | 
| Initial Dose of CT-P13 Infusion Administered to Participants | Initial dose of CT-P13 infusion (dose at the time of CT-P13 treatment initiation) was reported in this outcome measure. | At Day 1 of 2 year observation period | 
| Number of Participants by Initial Frequency of CT-P13 Infusion Received | Initial frequency of CT-P13 infusion was categorized as: once every 4, 6, 8 weeks and other. 'Other' included all other frequencies other than specified. Number of participants by baseline infusion frequency (in weeks) were reported. | Baseline (Day 1) of 2 year observation period | 
| Total Dose of CT-P13 Infusion Received During Observation Period | Total dose of infusion received by the participants were evaluated. | During the observation period of 2 years | 
| Number of Participants With Change in CT-P13 Infusion Dose | Participants who had change in the dose of infusion (either dose reduction or increase in dose) during the observation period were reported. | During the observation period of 2 years | 
| Number of Participants Who Had At Least One Concomitant Medication Related to the Treatment of Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) | Concomitant medications included corticosteroids, non-steroidal anti- inflammatory drugs (NSAID'S) and immunosuppressant. Participants were counted in more than one categories. 'Others' included DMARDS and other medications apart from the categories specified. | During the observation period of 2 years | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | 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 2 years, that were absent before treatment or that worsened relative to pretreatment state. Serious infections including sepsis (excluding opportunistic infections and tuberculosis) were the pre-defined TEAE of special Interest for this study. AEs included both serious and non-serious adverse events. | During the observation period of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Score-28 (DAS28) in Participants With Rheumatoid Arthritis (RA) at Months 6, 12, 18 and 24 | DAS28 calculated from the number of tender joint count (TJC) and swollen joint count (SJC) using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeters per hour; ranged from 0 to 150), and a participant's general health assessment (GH) on a 100 millimeter (mm) visual analog scale (VAS) (ranging from 0 mm [very well] to 100 mm [extremely bad], higher scores indicated worsening of health condition). Total DAS28 score ranged from 0 (none) to 9.4 (extreme disease activity), higher scores indicated more disease activity. DAS28 less than or equal to (<=) 3.2 implied low, greater than (>) 3.2 to <=5.1 implied moderate, and >5.1 implied high disease activity. DAS28=0.56*sqrt(28TJC)+0.28*sqrt(28SJC)+0.70*ln(ESR)+0.014*GH; where ln = natural logarithm and sqrt = square root of. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in Disease Activity Score-28 (DAS28) in Participants With Psoriatic Arthritis (PsA) at Months 6, 12, 18 and 24 | DAS28 calculated from the number of TJC and SJC using 28 joints count, ESR (millimeters per hour; ranged from 0 to 150), and participant's GH on a 100 mm VAS (ranging from 0 mm [very well] to 100 mm [extremely bad], higher scores indicated worsening of health condition). Total DAS28 score ranged from 0 (none) to 9.4 (extreme disease activity), higher scores indicated more disease activity. DAS28 <= 3.2 implied low, > 3.2 to <=5.1 implied moderate, and >5.1 implied high disease activity. DAS28=0.56*sqrt(28TJC)+0.28*sqrt(28SJC)+0.70*ln(ESR)+0.014*GH; where ln = natural logarithm and sqrt = square root of. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Participants With Ankylosing Spondylitis (AS) at Months 6, 12, 18 and 24 | BASDAI is a self-reported measure of disease activity in participants with AS. Participants answered 6 questions measuring symptoms of AS (fatigue, spinal pain, joint pain or swelling, areas of localized tenderness, morning stiffness duration and severity). The BASDAI total score was calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q) 1-4. This score was then divided by 5. BASDAI=Q1+Q2+Q3+Q4+[Q5+Q6/2]/5. The total BASDAI score ranges from 1=none to 10=severe, where lower score indicated less disease activity. The level of AS disease activity was interpreted as low (BASDAI < 4) or high (BASDAI > 4). | Baseline, Weeks 6, 12, 18 and 24 | 
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) in Participants With Ankylosing Spondylitis (AS) at Months 6,12,18 and 24 | ASDAS is used to assess disease activity in participants with AS. It is a score combining the assessment of overall pain (Q1), duration of morning stiffness (Q2), peripheral pain/swelling (Q3), PtGA (assessed on a sale of 0 to 10, where 0 = not active and 10=very active), and C-reactive protein (CRP) in milligrams per liter (mg/L). ASDAS total score was derived using the following formula: ASDAS=0.12*Q1+0.06*Q2+0.11*GH+0.07*Q3+0.58*ln (CRP+1). The level of AS disease activity was interpreted as inactive disease (ASDAS< 1.3), moderate disease activity (1.3 <= ASDAS < 2.1), high disease activity (2.1<= ASDAS <=3.5) and very high disease activity (ASDAS > 3.5). | Baseline, Weeks 6, 12, 18 and 24 | 
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) in Participants With Ankylosing Spondylitis (AS) at Months 6, 12, 18 and 24 | BASFI is a validated self assessment tool to determine the degree of functional limitation in participants with AS. It is comprised of 10 questions which were answered by participants using a VAS ranging from 0 (being easy) to 10 (impossible). BASFI total score was calculated as the average score of the 10 questions, and ranges from 0 (no functional impairment) to 10 (maximal impairment), higher scores indicated more impairment. | Baseline, Weeks 6, 12, 18 and 24 | 
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Months 6, 12, 18 and 24 | HAQ-DI assesses the degree of difficulty a participant had experienced in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale from 0 to 3 with 0 =no difficulty, 1 =some difficulty, 2 = much difficulty, and 3 =unable to do. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 = no difficulty to 3 =unable to do. Higher score indicate more difficulty in performing daily living activities. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in European Quality of Life- 5 Dimensions 3 Level Version (EQ-5D-3L) Visual Analog Scale (VAS) Score at Months 6, 12, 18 and 24 | EQ-5D-3L is a standardized, participant-administered measure of health outcomes. It consists of two parts: EQ-5D descriptive system (Part I) and the EQ-VAS (Part II). EQ-5D-3L Part II uses a vertical graduated VAS to measure health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Index Score at Months 6, 12, 18 and 24 | EQ-5D-3L is a standardized, participant-administered measure of self-reported health outcomes. It consists of two parts: EQ-5D descriptive system (Part I) and the EQ-VAS (Part II). For Part I, i.e. EQ-5D-3L index score, participants rated their current health state on 5 single-item dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with each dimension having three levels of function:. 1=no problems, 2=some problems and 3=extreme problems. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total score range of -0.074 to 1.00; higher scores indicating a better health state. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in Physical Component Summary (PCS) Score of Short Form 12 Version 2 (SF-12v2) Health Survey at Months 6, 12, 18 and 24 | The SF-12v2 is a self-administered, validated, multipurpose SF questionnaire to measure generic health status. It consists of 12 items, which are categorized into eight domains (subscales) of functioning and well-being: physical function, role limitations due to physical problems, bodily pain, general health perceptions, energy and vitality, social functioning, role limitations due to emotional problems, and mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. These eight domains are further summarized into PCS and mental component summary (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health). Higher scores indicated a better health-related quality of life. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in Mental Component Summary (MCS) Score of Short Form 12 Version 2 (SF-12v2) Health Survey at Months 6, 12, 18 and 24 | The SF-12v2 is a self-administered, validated, multipurpose SF questionnaire to measure generic health status. It consists of 12 items, which are categorized into eight domains (subscales) of functioning and well-being: physical function, role limitations due to physical problems, bodily pain, general health perceptions, energy and vitality, social functioning, role limitations due to emotional problems, and mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. These eight domains are further summarized into PCS and mental component summary (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health). Higher scores indicated a better health-related quality of life. | Baseline, Months 6, 12, 18 and 24 | 
| Change From Baseline in Physician Global Assessment (PGA) of Rheumatoid Diseases Activity at Months 6, 12, 18 and 24 | PGA of disease activity was measured on a 0 to 100 mm VAS, where 0 mm = no disease activity and 100 mm = extremely active. Higher scores indicated worsening of condition. | Baseline, Months 6, 12, 18 and 24 | 

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