Systemic Lupus Erythematosus
Conditions
Keywords
Chronic autoimmune disease, Immunosuppressants, Corticosteroids, Human monoclonal antibody (IgG1ƙ mAb), Post Marketing Requirements (PMR) study, Pregnancy, Systemic Lupus Erythematosus
Brief summary
PRIMULA Preg (Prospective Registry Investigating Maternal and Infant Outcomes in Anifrolumab Users) is a prospective, observational cohort study designed to evaluate the association between anifrolumab exposure during pregnancy and subsequent adverse maternal, fetal, and infant outcomes. This study will fulfil an FDA post-marketing requirement.
Detailed description
PRIMULA Preg (Prospective Registry Investigating Maternal and Infant Outcomes in Anifrolumab Users) is a US-based, prospective, observational cohort study designed to evaluate the association between anifrolumab exposure during pregnancy and subsequent adverse maternal, fetal, and infant outcomes. The objective of the pregnancy registry is to compare adverse maternal, fetal, and infant outcomes of pregnant individuals with moderate/severe systemic lupus erythematosus (SLE) who are exposed to anifrolumab during pregnancy with outcomes in an internal comparison cohort of pregnant individuals with moderate/severe SLE who are not exposed to anifrolumab during pregnancy. Participation in the registry is voluntary and participants can withdraw their consent to participate at any time. The study is strictly observational; the schedule of office visits and all treatment regimens will be determined by HCPs. Only data that are documented in patients' medical records during medical care will be actively collected. No additional laboratory tests or HCP assessments will be required as part of this registry. This study will fulfil an FDA post-marketing requirement.
Interventions
DRUGAnifrolumab
Anifrolumab is a human monoclonal antibody that binds to subunit 1 of the type 1 interferon receptor, which was developed based on the evidence supporting the role of type 1 interferon pathway in SLE. Clinical trial evidence from TULIP 1 and TULIP 2 have showed that monthly intravenous administration of anifrolumab led to a higher percentage of patients with a response, assessed with the British Isles Lupus Assessment Group-based Composite Lupus Assessment, compared with patients receiving placebo. Moreover, the phase II MUSE study showed that administration of anifrolumab resulted in substantially reduce disease activity, as measured by the SLE Responder Index, compared to patients receiving placebo. Anifrolumab was approved by the FDA and EMA in July 2021 and February 2022, respectively, for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy.
Sponsors
AstraZeneca
PPD Development, LP
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
Exposed cohort 1. Currently or recently (within 1 year of pregnancy outcome) pregnant 2. Diagnosis of moderate/severe SLE 3. Consent to participate 4. Authorization for their HCP(s) to provide data to the registry 5. Exposure to at least 1 dose of anifrolumab at any time during pregnancy Unexposed cohort 1. Currently or recently pregnant 2. Diagnosis of moderate/severe SLE 3. Consent to participate 4. Authorization for their HCP(s) to provide data to the registry 5. Exposure to other products for the treatment of moderate/severe SLE
Exclusion criteria
Exposed cohort 1. Occurrence of pregnancy outcome prior to first contact (for enrollment) with the Virtual Research Coordination Center (retrospectively enrolled) 2. Exposure to known teratogens and/or investigational medications during pregnancy Unexposed cohort 1. Occurrence of pregnancy outcome prior to first contact with the Virtual Research Coordination Center (retrospectively enrolled) 2. Exposure to known teratogens and/or investigational medications during pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome of all major congenital malformations (MCMs) | From date of conception (DOC) to pregnancy outcome for fetal losses or 12 months of infant age for live births | An abnormality of body structure or function that is present at birth, is of prenatal origin (i.e., birth defect), has significant medical, social, or cosmetic consequences for the affected individual, and typically requires medical intervention. Relevant exposure window is limited to 1st trimester of pregnancy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome of all minor congenital malformations | From date of conception (DOC) to pregnancy outcome for fetal losses or 12 months of infant age for live births | An anomaly or abnormality of body structure that is present at birth, is of prenatal origin (i.e., birth defect), poses no significant health problem in the neonatal period, and tends to have limited social or cosmetic consequences for the affected individual. Relevant exposure window includes any trimester of pregnancy. |
| Worsening of underlying disease | From date of conception (DOC) to pregnancy outcome, up to 42 weeks of pregnancy | Any increase in disease activity or severity in the pregnancy period compared to the baseline period (6 months prior to pregnancy) as assessed by the disease flare or disease activity algorithms or as reported by an HCP. Relevant exposure window includes any trimester of pregnancy. |
| Premature rupture of membranes | From date of conception (DOC) to pregnancy outcome, up to 42 weeks of pregnancy | A disorder of pregnancy defined as rupture of membranes before the onset of labor. Relevant exposure window includes any trimester of pregnancy. |
| Pregnancy-induced hypertension | From 20 gestational weeks to pregnancy outcome, up to 42 weeks of pregnancy | A disorder of pregnancy defined as a systolic blood pressure 140 mmHg or more or a diastolic blood pressure of 90 mmHg or more, or both, on 2 occasions at least 4 hours apart after 20 weeks gestation, in a woman with a previously normal blood pressure. Relevant exposure window includes any trimester of pregnancy. |
| Composite outcome of preeclampsia/eclampsia | From 20 gestational weeks to pregnancy outcome, up to 42 weeks of pregnancy | Preeclampsia is a disorder of pregnancy associated with new-onset hypertension, which occurs most often after 20 weeks of gestation and frequently near term, and proteinuria. Or, in the absence of proteinuria, it is defined as new-onset hypertension with the new onset of any of the following: * Thrombocytopenia: platelet count less \<100 ,000/mL * Renal insufficiency: serum creatinine concentrations \>1.1mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease * Impaired liver function: elevated blood concentrations of liver transaminases to twice normal concentration * Pulmonary edema * New-onset headache unresponsive to medication and not accounted for by alternative diagnoses or visual symptoms. Eclampsia is new-onset tonic-clonic, focal, or multifocal seizures in the absence of other causative conditions such as epilepsy, cerebral arterial ischemia and infarction, intracranial hemorrhage, or drug use. |
| Maternal hospitalization for serious illness | From date of conception (DOC) to pregnancy outcome, up to 42 weeks of pregnancy | An inpatient hospital admission unrelated to delivery occurring during pregnancy. Relevant exposure window includes any trimester of pregnancy. |
| Spontaneous abortion | From date of conception (DOC) to <20 gestational weeks | An involuntary fetal loss or the expulsion of the products of conception occurring at \<20 gestational weeks. |
| Elective termination | From date of conception (DOC) to pregnancy outcome, up to 24 weeks of pregnancy | An intervention that is intended to terminate a suspected or known ongoing intrauterine pregnancy and that does not result in a live birth. Relevant exposure window includes any trimester of pregnancy. |
| Emergency caesarean section | From date of conception (DOC) to pregnancy outcome, up to 42 weeks of pregnancy | A cesarean delivery that is performed due an immediate threat to the health or safety of the fetus and/or the mother. Relevant exposure window includes any trimester of pregnancy. |
| Preterm birth | From date of conception (DOC) up to 37 gestational weeks | A live birth occurring at \<37 gestational weeks. |
| Small for gestational age | At delivery of live birth | Birthweight \<10th percentile for sex and gestational age using standard growth charts for full and preterm live-born infants. Relevant exposure window includes any trimester of pregnancy. |
| Postnatal growth deficiency | At 4 and 12 months of infant age | Weight, length, or head circumference in \<10th percentile for sex and chronological age using standard growth charts. Relevant exposure window includes any trimester of pregnancy. |
| Infant developmental delay | At 4 and 12 months of infant age | Failure to achieve the developmental milestones for chronological age, as defined by the CDC. Relevant exposure window includes any trimester of pregnancy. |
| Infant hospitalization for serious illness | From birth to 1 year of infant age | An inpatient hospital admission occurring in the first year of life. Relevant exposure window includes any trimester of pregnancy. |
| Infant serious or opportunistic infection | From birth to 1 year of infant age | An infection that occurs within an infant's first year of life and is either opportunistic (i.e., occurs more often or is more severe in people with weakened immune systems than in people with healthy immune systems) or serious (i.e., results in significant disability, incapacity, or death; is life-threatening; requires inpatient or prolonged hospitalization; or is considered medically important). Relevant exposure window includes any trimester of pregnancy. |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed