Status: Planned
First registered on:
30/08/2019
Last updated on:
02/09/2019
1. Study identification
EU PAS Register NumberEUPAS31199
Official titleEvaluation of the risks of biologic drugs exposure during pregnancy in patients with rheumatic chronic inflammatory diseases: data from the French national healthcare data system (SNDS)
Study title acronymBIOGRIC
Study typeObservational study
Brief description of the studyRheumatoid arthritis (RA) psoriatic arthritis (PsoA) and Spondyloarthritis (SpA) are the most frequent rheumatic chronic inflammatory disease (RCID) in women of childbearing age, and can lead to permanent joint destruction and disability. Biologics, in particular TNF inhibitors (TNFi), have dramatically improved the outcome of these patients; nevertheless, an increased infectious risk related to these drugs has been reported.
The main aim of this study is to compare the risks of a 'poor pregnancy outcome' in exposed vs not exposed to TNFi RCID patients.
Secondary aims are:
a) To describe the treatment of RA, SpA or PsoA during pregnancy regarding:
• Non-steroidal-anti-inflammatory drugs and corticosteroids;
• Conventional disease-modifying anti-rheumatic drugs (DMARDs);
• Biologic DMARDs: TNFi and other biologics.
b) To compare, in women with RA, SpA or PsoA exposed to TNFi vs unexposed women, the risks of maternal and perinatal infections, congenital malformations and gestational diabetes
c) To evaluate the risk of above-described outcomes in pregnant patients exposed to other biologics during pregnancy in RA, SpA or PsoA women.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research groupCentre de pharmaco-épidémiologie
Organisation/affiliationAssistance Publique - Hôpitaux de Paris
Details of (Primary) lead investigator
Title Dr
Last name Molto
First name Anna
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
France
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/01/201901/01/2019
Start date of data collection31/12/2019
Start date of data analysis31/12/2019
Date of interim report, if expected
Date of final study report31/01/2021
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government bodyDGOS – PHRC-N100
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Molto
First name Anna
Address line 1Rheumatology department – Cochin hospital
Address line 227 Rue du Faubourg Saint-Jacques
Address line 3
CityParis
Postcode75014
CountryFrance
Phone number (incl. country code)33158412619
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Molto
First name Anna
Address line 1Rheumatology department – Cochin hospital
Address line 227 Rue du Faubourg Saint-Jacques
Address line 3
CityParis
Postcode75014
CountryFrance
Phone number (incl. country code)33158412619
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)L04AB (Tumor necrosis factor alpha (TNF-a) inhibitors)
7. Medical conditions to be studied
Medical condition(s)Yes
Rheumatoid arthritis
Psoriatic arthropathy
Spondylitis
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Sex
Female
Other population
Pregnant women
9. Number of subjects
Estimated total number of subjects84100
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources not registered with ENCePP
SNDS, France
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Risk assessment
Drug utilisation study
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To compare the risks of poor pregnancy outcomes in patients with RA, SpA or PsoA exposed to TNFi versus unexposed patients with RA, SpA or PsoA.
Are there primary outcomes?Yes
Poor pregnancy outcome: intrauterine growth restriction, therapeutic abortion, stillbirth (death of a fetus with a gestational age ≥ 22 weeks or birth weight > 500gr), preterm delivery, perinatal mortality, maternal hospitalization due to infection, small for gestational age (birth weight < 3th percentile) or hospitalization in neonatal intensive care unit at 37 weeks.
Are there secondary outcomes?Yes
- Treatment during pregnancy: NSAID, corticoids, conventional and biologic DMARDS
- All the individual items of the composite main outcome
- Severe and non-severe maternal infections, severe perinatal infections of the offspring, severe infections of the offspring the first year of life, severe congenital malformations, gestational diabetes, spontaneous and elective abortions, preterm delivery.
13. Study design
What is the design of the study?
Cohort study
Drug utilisation study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Each woman will be followed-up from 6 months before start of pregnancy until the pregnancy termination + 6 weeks (or death if it occurs before). Only the first pregnancy of each woman will be considered for the principal analysis. Subsequent pregnancies will be taken into account in sensitivity analyses.
New-borns will be followed up to the age of 1 year or death, whichever occurs first.
15. Data analysis plan
Please provide a brief summary of the analysis method
The main analysis focuses on the comparison of event risk between women exposed to TNFi and women not exposed to biologics (therefore pregnancies that are exposed to another biologic than a TNFi will be excluded from this analysis). Event rates will be compared by a logistic model. To account for the fact that exposed women are likely to be different from unexposed women, a propensity score will be constructed using both pregnancy-related variables and underlying rheumatologic disease variables.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Not submitted
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
