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

Rheumatoid Arthritis Clinical Trial

— PERSIST  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02605642
• Other study ID #: ZOBINF1505
• Secondary ID: C1231002
• Status: Completed
• Start date: September 10, 2015
• Est. completion date: December 31, 2018

Study information

• Verified date: December 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients aged =18 years old at the time of enrollment

2. 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:

1. Any reported contraindications for Inflectra according to the SmPC or Product Monograph

2. Known hypersensitivity (including severe, acute infusion reactions) to infliximab, its excipients or other murine proteins, at the time of enrollment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Rheumatoid Diseases
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• CT-P13
biosimilar infliximab

Locations

Country	Name	City	State
Bulgaria	MHAT Kaspela EOOD	Plovdiv
Bulgaria	MHAT Trimontium OOD	Plovdiv
Bulgaria	Diagnostic Consultative Center 17 Sofia EOOD	Sofia
Canada	The Waterside Clinic	Barrie	Ontario
Canada	William Osler Health System	Brampton	Ontario
Canada	Lucere Skin Dermatology & Laser Clinic	Edmonton	Alberta
Canada	Adachi Medicine Professional Corporation	Hamilton	Ontario
Canada	K-W Musculoskeletal Research Inc	Kitchener	Ontario
Canada	Y. Liu Medicine Professional	Milton	Ontario
Canada	Credit Valley Imaging Associates	Mississauga	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal - Notre-Dame Hospital	Montreal	Quebec
Canada	Oakville Rheumatology & Osteoporosis	Oakville	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Groupe de Recherche en Rhumatologie et Maladies Osseuses (GRMO)	Quebec
Canada	Centre Rhumatologie de l'Est	Rimouski	Quebec
Canada	Nexus Clinical Research	St. John's	Newfoundland and Labrador
Canada	Dr. Juris Lazovskis Inc.	Sydney	Nova Scotia
Canada	Arthur Karasik Medicine Professional Corporation	Toronto	Ontario
Canada	Centre de Recherche Musculo-Squelettique	Trois-Rivières	Quebec
Canada	Dr. Sabeen Anwar Medicine Professional Corporation	Windsor	Ontario
Czechia	Revmatolog Mudr. Sirova Klara s.r.o.	Ostrava
Czechia	Revmatologický Ústav (RÚ)	Praha 2
Germany	Rheumapraxis Steglitz	Berlin
Germany	Immanuel Diakonie GmbH	Bernau
Germany	Rheumatologisches MVZ Dresden GmbH	Dresden
Germany	Asklepios Gesundheitszentrum Elmshorn	Elmshorn
Germany	Rheumatologische Praxis Dr. med. Kühne	Haldensleben
Germany	Dr. med. Jörg Kaufmann	Ludwigsfelde
Germany	Praxis Dr. Herbert Kellner	Muenchen
Germany	MVZ für Rheumatologie Dr. Martin Welcker GmbH	Planegg
Germany	Berufsausübungsgemeinschaft Martin Bohl-Bühler & Dr. med. Sabine Reckert	Potsdam
Germany	Dr. med. Jochen Walter - FA für Innere Medizin Rheumatologe	Rendsburg
Greece	University General Hospital of Heraklion	Heraklion	Crete
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña A Coruña
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Canarias	San Cristóbal de La Laguna
United Kingdom	Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital	Portsmouth
United Kingdom	Salisbury NHS Foundation Trust - Salisbury District Hospital	Sailsbury

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Hospira, now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

Bulgaria,  Canada,  Czechia,  Germany,  Greece,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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