National Observational Study On The Use Of Inflectra™ An Infliximab Biosimilar In Real Life

Study Overview
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Brief Summary
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National, prospective, multicentre observational study designed for eligible patients treated with Inflectra. Its objectives are to describe under real conditions of use, the profile of patients treated with Inflectra and the response to treatment.

Official Title
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OBSERVATOIRE NATIONAL D'UTILISATION D'INFLECTRA™ EN VIE RÉELLE.

Conditions
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Ulcerative Colitis, Crohn Disease, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis

Intervention / Treatment
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* Other: QOL questionaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients treated with Inflectra™ regardless of treatment phase in one of the following indications consistent with the SPC: Crohn's Disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis. Paediatric patients (children and adolescents between 6 and 17 years old) treated with Inflectra™, regardless of treatment phase from the time when Inflectra™ is prescribed in accordance with the indications listed in the SPC Crohn's Disease or ulcerative colitis Patients (or their legal representatives) who have received information (verbally and in writing) about the study and agreed to take part in it. Patients who have given their agreement for their clinical data and their medical file to be accessed by signing the information leaflet. Exclusion Criteria: Patients who refuse access to their medical file for collection of: their medical data Patients not treated with Inflectra™. Patients treated with Inflectra™ for psoriasis. Patients with a past history of hypersensitivity to infliximab, to other murine proteins or to one of the excipients in Inflectra™. Patients with tuberculosis or any other severe infection such as sepsis, abscess or opportunistic infection . Patients with moderate to severe heart failure (NYHA III/IV)

Ages Eligible for Study
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Minimum Age: 6 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 |
| --- | --- |
| Patients treated with Inflectra<br> | Other: QOL questionaire<br>* Health assessment questionnaire disability index for rheumatoid polyarthritis questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Without Treatment Failure During 2-Years of Observation | Treatment failure was defined as permanent discontinuation of the Inflectra treatment due to intolerance and/or permanent discontinuation of treatment due to absence of response according to the physician's assessment, or death of the participant related to Inflectra. In this outcome measure percentage of participants without treatment failure and whose data were missing are reported. | 2 years post inclusion in the study | 
| Number of Participants With Pre-treatment Assessment Prior to Initiation of Inflectra Treatment (Anti-Tumor Necrosis Factor [TNF] Aplha) Therapy | Pre-treatment assessment was a check-list with the set of measures determined by the physician to check the eligibility of a participant before initiation of treatment. Physician recorded as Yes if a participant was eligible for initiation of treatment and No if a participant was not eligible to initiate a treatment. In this outcome measure, number of participants whose pre-treatment assessment were performed prior to initiation of Inflectra are reported and whose data were missing are reported. | Data collected and recorded at study inclusion visit | 
| Time Between Diagnosis and Inclusion in Study |  | Data collected and recorded at study inclusion visit | 
| Time Between Diagnosis and the First Inflectra Infusion |  | Data collected and recorded at study inclusion visit | 
| Number of Participants Who Received Biotherapy Other Than Inflectra Before Inclusion in the Study | Type of biotherapies received by participants before inclusion in the study were: anti-TNF alpha (remicade/ adalimumab/ golimumab / etanercept/ rituximab); anti-integrin (vedolizumab); immunosuppressant (abatacept); interleukin inhibitor (anakinra / tocilizumab); anti interleukin (IL) 12 and anti IL-23 (ustekinumab); and other. In this outcome measure number of participants who received biotherapies other than Inflectra and whose data were missing are reported. | Data collected and recorded at study inclusion visit | 
| Number of Participants With Reasons for Discontinuation of Previous Biotherapy | Type of previous biotherapies included were: anti-TNF alpha (infliximab/adalimumab/etanercept/golimumab), selective immuno-suppressant (vedolizumab/abatacept), interleukin inhibitor (anakinra/ustekinumab/tocilizumab), and other. In this outcome measure, number of participants who discontinued previous biotherapy are reported according to reason of discontinuations. | Data collected and recorded at study inclusion visit | 
| Duration of Previous Biotherapies | Type of previous biotherapies included were: anti-TNF alpha (infliximab/adalimumab/etanercept/golimumab), selective immuno-suppressant (vedolizumab/abatacept), interleukin inhibitor (anakinra/ustekinumab/tocilizumab), and other. | Data collected and recorded at study inclusion visit | 
| Mean of Number of Doses Administered in Previous Biotherapy | Type of previous biotherapies included were: anti-TNF alpha (infliximab/adalimumab/etanercept/golimumab), selective immuno-suppressant (vedolizumab/abatacept), interleukin inhibitor (anakinra/ustekinumab/tocilizumab), and other. In this outcome measure mean of number of doses administered in previous biotherapy is reported. | Data collected and recorded at study inclusion visit | 
| Last Dosage Administered of a Previous Biotherapy | Type of previous biotherapies included were: anti-TNF alpha (infliximab/adalimumab/etanercept/golimumab), selective immuno-suppressant (vedolizumab/abatacept), interleukin inhibitor (anakinra/ustekinumab/tocilizumab), and other. In this outcome measure mean of last dosage (in units) of previous biotherapy administered dose is reported. | Data collected and recorded at study inclusion visit | 
| Number of Participants Who Received Concomitant Treatments Prior to Initiation of Inflectra | Following concomitant treatments were received by participants before initiation of Inflectra: 1) Corticosteroids, 2) Salicylates, and 3) Azathioprine/6-MP, Methotrexate, and Cyclosporine. | Data collected and recorded at study inclusion visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician Global Assessment (PGA) of Disease for RA, SpA and PA | PGA was evaluated in participants with RA, SpA and PA on a 0 to 10 centimeter (cm) visual analog scale (VAS), with 0 cm = no disease activity and 10 cm = worst disease activity possible. Higher scores indicated worse condition. | 24 months | 
| Mean Administered Dose of Inflectra (in mg) | Mean dose (in milligrams [mg]) administered was sum of dose of all infusions administered divided by total number of doses administered. | Inclusion visit up to 6-Month visit, 6-Month visit to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Mean Administered Posology of Inflectra (in mg/kg) | Mean posology administered was sum of posology of all infusions administered divided by total number of infusions administered. Posology = dose (mg) / weight (kg). | Inclusion visit up to 6-Month visit, 6-Month visit to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Cumulative Dose | Cumulative dose is the sum of doses administered during inclusion visit to month 6, 12, 18, and 24. | Inclusion visit up to 6-Month visit, Inclusion visit up to 12-Month visit, Inclusion visit up to 18-Month visit, and Inclusion visit up to 24-Month visit | 
| Mean Infusion Time | Mean infusion time was sum of duration of all infusions administered divided by total number of infusion times administered. | Inclusion visit up to 6-Month visit, 6-Month visit to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Mean Time Between Infusions |  | Inclusion visit up to 6-Month visit, 6-Month visit to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Mean Duration of Post-infusion Monitoring at the Hospital | Mean post-infusion monitoring at hospital was sum of duration of all monitoring at hospital divided by total number monitoring times. | Inclusion visit up to 6-Month visit, 6-Month visit to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Absolute Variation in Mean Disease Activity Score (DAS) 28 Compared With Baseline at Month 6, 12, 18, and 24 | DAS28 score was evaluated in participants with RA and PA. DAS28 is calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (in millimeters per hour [mm/hour]) and participant's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with scores ranging 0 to 10; higher scores indicated high disease activity). DAS28 was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR [mm/first hour] + 0.014 (PtGA [mm]). Total score range: 0-9.4. DAS 28 score <=2.6 indicated remission in disease, score between >2.6 and <=3.2 indicated mildly active disease, score between >3.2 and <=2.6 indicated moderately active disease, and score >5.1 indicated very active disease. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Compared With Baseline at Month 6, 12, 18, and 24 | BASDAI is a set of 6 questions to determine disease activity in participant with SpA. Participants answered each 6 questions on a scale of 0 (no problem) to 10 (the worst problem). The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q) 1-4. This score is then divided by 5. BASDAI score = (Q1 + Q2 + Q3+ Q4+ [Q5 + Q6/2])/5. BASDAI score ranges from 0 (best) to 10 (worst), where higher scores meant worse condition. BASDAI score >4 indicated SpA active, and score <=4 indicated SpA inactive. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Bath Ankylosing Spondylitis Functional Index (BASFI) Score Compared With Baseline at Month 6, 12, 18, and 24 | BASFI is a set of 10 questions to determine degree of functional limitation in participants with SpA. Participants answered each 10 questions on a scale of 0 (no functional impairment) to 10 (maximal impairment). BASFI score was calculated as mean of scores from 10 questions. BASFI score ranged from 0 (no functional impairment) to 10 (maximal impairment), where higher scores meant worse condition. Score >4 indicated significant functional impairment, and score <=4 indicated mild functional impairment. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Mayo Score Compared With Baseline at Month 6, 12, 18, and 24 | Mayo score was evaluated in participants with UC. Mayo score consists of 4 items (stool frequency, rectal bleeding, findings of endoscopy, physician global assessment), each graded from 0 (no severity) to 3 (maximum severity), with higher scores indicating more severe disease. Total score was sum of 4 items resulting in a score range of 0 (no severity) to 12 (maximum severity), where higher score indicated increased severity. Score <=2 indicated UC inactive, score between >=3 and <=5 indicated mild UC, score between >=6 and <=10 indicated moderate UC, and score >11 indicated severe UC. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Pediatric Ulcerative Colitis Activity Index (PUCAI) Score Compared With Baseline at Month 6, 12, 18, and 24 | PUCAI score was intended for pediatric participants with UC. PUCAI had 6 items with scores as: abdominal pain (no pain =0, pain can be ignored =5, pain cannot be ignored =10); rectal bleeding (none =0, small amount only [in less than 50% of stools] =10, small amount with most stools =20, large amount [>50% of the stool content] =30); stool consistency of most stools (formed =0, partially formed =5, completely unformed =10); number of stools per 24 hours (0-2 =0, 3-5 =5, 6-8 =10, >8 =15); nocturnal stools (no =0, yes =10); activity level (no limitation of activity =0, occasional limitation of activity =5, severely restricted activity =10). PUCAI score = sum of scores of 6 items; score range of 0= no severity to 85= extreme severity. PUCAI score <10: UC in remission, score between >=10 and <35: mild UC, score between >=35 and <65: moderate UC, and score >=65: severe UC. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Colitis Endoscopic Index of Severity (UCEIS) Score Compared With Baseline at Month 6, 12, 18, and 24 | UCEIS score was evaluated in participants with indication UC. It had 3 sub-scales: endoscopic vascular pattern (scored 0 [normal pattern] to 2 [complete obliteration of vascular pattern]), bleeding (scored 0 [none] to 3 [luminal moderate or severe]), erosions and ulcerations (scored 0 [none] to 3 [deep ulcers]). UCEIS total score was calculated by sum of all 3 sub-scale scores. Total score ranged from 0 (remission in disease) to 8 (extreme severity of disease), with higher scores indicating more severe disease. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Harvey-Bradshaw Score Compared With Baseline at Month 6, 12, 18, and 24 | Harvey-Bradshaw score was evaluated for indication CD. Harvey-Bradshaw measures 5 parameters; general well-being (0= very well to 4= terrible), abdominal pain (0= none to 3= severe), number of liquid stools per day (0 to no maximum score), presence of an abdominal mass on physical exam (0= none to 3= definite and tender), and whether there are any complications (0= no complications, 1= arthralgia, 2= uveitis, 3= erythema nodosum, 4= aphthous ulcer, 5= pyoderma gangrenosum, 6= anal fissure, 7= new fistula, 8= abscess). Total HBI score: sum of all 5 individual parameters, minimum score is 0 and there was no pre-specified maximum score as it depended on number of liquids stools. Higher HBI scores = greater disease activity score <4 indicated Inactive disease, score >=4 and/or <=12 indicated Active disease, and score >12 indicated Very active disease. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Crohn's Disease Endoscopic Index of Severity (CDEIS) Score Compared With Baseline at Month 6, 12, 18, and 24 | CDEIS is an index for determining the severity of CD with endoscopic localization to ileum and colon. CDEIS considered 4 parameters: deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis. These 4 parameters were evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). CDEIS score ranged from 0 (no lesions) to 44 (severe lesions) where higher scores indicate more severity. CDEIS score <=7 indicated Endoscopic remission, and score >7 indicated Absence of endoscopic remission. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation of Mean Global Disease Assessment Compared With Baseline at Month 6, 12, 18, and 24 | The global disease assessment by the physician for participants with RA, SpA and PA was evaluated on a 0 to 10 cm VAS, with 0 cm = no disease activity and 10 cm = worst disease activity. Higher scores indicated worse condition. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation of Mean Fatigue Score Compared With Baseline at Month 6, 12, 18, and 24 | Fatigue score was evaluated among participants with RA, SpA, and PA. Participants' fatigue severity was measured on a VAS with a score range of 0 (no fatigue) to 10 (highest level of fatigue). Higher score signifies more severity. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Simple Disease Activity Index (SDAI) Score Compared With Baseline at Month 6, 12, 18, and 24 | SDAI was evaluated in participants with indication RA. SDAI is the numerical sum of 5 parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0 (very well) -10 cm (worst) VAS; higher scores = greater affection due to disease activity, and C-reactive protein (CRP) (mg/dL). SDAI total score =0 (no disease) to 86 (extreme severity of disease), where higher scores indicated higher disease activity. SDAI score <=3.3 indicated achievement of remission state, score >3.3 and/or <=11 indicated mildly active state, score >11 and/or <=26 indicated moderately active state, and score >26 indicated very active state. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Health Assessment Questionnaire (HAQ) Score Compared With Baseline at Month 6, 12, 18, and 24 | HAQ score was evaluated for indication RA. HAQ assesses degree of difficulty participant had experienced during past week in 8 domains of daily activities: dressing & grooming, arising, eating, walking, hygiene, reach, grip and other activities. For each question in questionnaire, level of difficulty was scored from 0 (no difficulty) to 3 (unable to do). Any activity requiring assistance from another individual or required use of assistive device would adjust to minimum score of 2 to represent more limited functional status. Overall score = sum of scores divided by number of domains answered. Total possible score range was 0 (no difficulty) to 3 (unable to do). Higher score = more difficulty in performing daily living activities. HAQ score >0.5 indicated Existence of functional disability & HAQ score <=0.5 indicated Absence of functional disability. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Absolute Variation in Mean Ankylosing Spondylitis Disease Activity Score (ASDAS) Score Compared With Baseline at Month 6, 12, 18, and 24 | ASDAS score was evaluated for indication SpA. 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 [not active] to 10 [very active]), and CRP in mg/L. ASDAS total score ranged from 0 (no disease) to 10 (maximum severity), higher score indicates greater severity of disease and was derived using the following formula: ASDAS =0.12*Q1 + 0.06*Q2 + 0.11* PtGA + 0.07*Q3 + 0.58*ln (CRP+1). ASDAS score <1.3 indicated SpA inactive, ASDAS score >=1.3 and/or <2.1 indicated SpA mildly active, ASDAS score >=2.1 and/or <=3.5 indicated SpA moderately active, and ASDAS score >3.5 indicated SpA very active. Absolute variation = mean result of laboratory test during period in question - result of laboratory test at baseline. | Baseline (Inclusion Visit), Month 6, 12, 18, and 24 | 
| Cook and Medley Score at Baseline | Cook-Medley questionnaire, also called cynical distrust scale, contained 8 items, scoring from 0 (trust) to 4 (no trust). The total score of the questionnaire was calculated by adding together the scores for the 8 items. Total possible score range was from 0 (trust) to 32 (no trust), higher score signifies greater cynical distrust. This outcome measure was evaluated in participants who were informed of a switch from infliximab reference to Inflectra. | Baseline (data recorded at inclusion visit) | 
| Stress Score | The questionnaire on stress after the switch to the biosimilar contained 3 items (emotional reactivity, repetition syndrome and tendency to avoid), each scored from 0 (no stress) to 4 (extreme stress). The overall score of stress was calculated by adding together the scores for the 3 items, ranged from 0 (no stress) to 12 (highest level of stress), higher scores indicated greater levels of stress. This outcome measure was evaluated in participants who were informed of a switch from infliximab reference to Inflectra. | Baseline (inclusion visit) up to Month 12 | 
| General Anxiety Disorder (GAD7) Score | GAD7: questionnaire of anxiety with 7 items, scoring from 0 (no anxiety) to 3 (extreme anxiety). The total GAD7 score was calculated by adding together the scores for the 7 items, ranged from 0 (no anxiety) to 21 (extreme anxiety), higher scores indicated severe anxiety. This outcome measure was evaluated in participants who were informed of a switch from infliximab reference to Inflectra. | Baseline (inclusion visit) through post each infusion (during 2 years) | 
| Number of Participants With Immunogenicity Assay at Inclusion Visit |  | Baseline (data recorded at inclusion visit) | 
| Number of Participants With Anti-Infliximab Antibody Assay Assessment at Inclusion Visit |  | Baseline (data recorded at inclusion visit) | 
| Number of Participants With Presence of Anti-infliximab Antibodies at Inclusion Visit |  | Baseline (data recorded at inclusion visit) | 
| Number of Participants With Infliximab Trough Level (IFX-TL) Assay at Inclusion Visit | Trough level was plasma concentration of drug before infusion. | Baseline (data recorded at inclusion visit) | 
| Infliximab Trough Level (IFX-TL) at Inclusion Visit | Trough level was plasma concentration of drug before infusion. | Before infusion at baseline (data recorded at inclusion visit) | 
| Mean of Number of Immunogenicity Assays Done (Inclusion Visit up to 6-Month Visit, 6-Month Visit up to 12-Month Visit, 12-Month Visit up to 18-Month Visit, and 18-Month Visit up to 24-Month Visit) |  | Inclusion visit up to 6-Month visit, 6-Month visit up to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Number of Participants With Presence of At-least 1 Anti-Infliximab Antibodies (Inclusion Visit up to 6-Month Visit, 6-Month Visit up to 12-Month Visit, 12-Month Visit up to 18-Month Visit, and 18-Month Visit up to 24-Month Visit) |  | Inclusion visit up to 6-Month visit, 6-Month visit up to 12-Month visit, 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit | 
| Mean Inflectra Trough Level (IFX-TL) (Inclusion Visit up to 6-Month Visit, 6-Month Visit up to 12-Month Visit, 12-Month Visit up to 18-Month Visit, and 18-Month Visit up to 24-Month Visit) | Trough level was plasma concentration of drug before infusion. In this outcome measure mean of all IFX-TLs for all infusions occurring during specified duration is reported. | Before every infusion occurred during: inclusion visit up to 6-Month visit; 6-Month visit up to 12-Month visit; 12-Month visit up to 18-Month visit, and 18-Month visit up to 24-Month visit |