Characterization of Pregnancy Outcomes in Women with Generalized Pustular Psoriasis

Study type
Protocol
Date of Approval
Study reference ID
23_003552
Lay Summary

Generalized Pustular Psoriasis (GPP) is a chronic, rare, and severe skin disease, which presents as repeated occurrence of flares affecting the skin and internal organs. GPP flares are unpredictable, potentially life-threatening and can lead to death. GPP flares can occur during pregnancy or be caused by pregnancy. GPP can also impact the management of the other disease and treatment decisions.

Specific treatments and guidelines for the management of GPP are lacking globally. A new drug Spesolimab, was recently shown to be effective in treating GPP flares in clinical trials. The US Food and Drug Administration (FDA) has required patients exposed to spesolimab before or during pregnancy to be observed for side-effects . To understand the impact of spesolimab exposure in pregnant women with GPP, robust knowledge of pregnancy outcomes in females with GPP is needed. Currently, data and available published literature are limited and insufficient to support our understanding of the pregnancy outcomes of women with GPP. Hence, this study is designed to provide a comprehensive description of pregnancy outcomes in population of women with GPP and newborn outcomes in babies born to mothers with GPP, in routine clinical practice. The data generated in this study will support increased detection of side-effects for patients exposed to spesolimab before or during pregnancy.

Technical Summary

Generalized Pustular Psoriasis (GPP) is a rare, severe, neutrophilic skin disease, associated with loss-of-function mutations in the interleukin-36 (IL-36) receptor antagonist gene and associated genes, which lead to overexpression of IL-36 cytokines. GPP is characterized by repeated occurrence of acute and unpredictable flares caused by systemic inflammation affecting the skin and internal organs, that can carry high morbidity, including hospitalization, and can lead to death. GPP flares can be induced or exacerbated by pregnancy.

GPP during pregnancy (i.e. impetigo herpetiformis), typically onsets in the third trimester, but the aetiology is uncertain. Women with GPP are at an increased risk of adverse pregnancy outcomes including intrauterine growth restriction, miscarriage, stillbirth and adverse fetal outcomes. However, data are limited regarding the pregnancy outcomes of women with GPP and newborn outcomes in babies born to women with GPP.
The overall aim is to evaluate the occurrence of pregnancy outcomes in the population of women diagnosed with GPP and newborn outcomes (identified at birth or during the neonatal period i.e. during the first 28 days of life) in babies born to women with GPP, globally.

To describe the occurrence of pregnancy/newborn outcomes, descriptive statistics will be provided for the study population. The crude cumulative incidence will be calculated and will be presented with corresponding 95% confidence intervals (CIs) for each pregnancy/newborn outcome in each country included in this study.

The data will provide insights into the occurrence of pregnancy outcomes in women with GPP including the newborn outcomes, globally. As well as crucial insights into how patients with GPP can be managed and monitored in England and Wales to improve the pregnancy and newborn outcomes in this patient group. Furthermore, this data will increase the understanding of current unmet need in women with GPP, and indirectly inform public health policy.

Health Outcomes to be Measured

The primary outcome of interest in this study will be pregnancy outcomes. These include complications or clinical conditions occurring during pregnancy as well as outcomes relating to delivery and birth. The clinical conditions occurring during pregnancy include conditions such as but not limited to, antenatal haemorrhage, ectopic pregnancy, erythroderma, gestational diabetes, Pregnancy-induced hypertension, complication occurring during labor and delivery, Infectious disease in mother complicating pregnancy or childbirth and pre-eclampsia. The outcomes relating to delivery and birth include outcomes such as live birth, miscarriage, stillbirth, caesarean section.

As secondary outcomes, this study will assess newborn outcomes identified at birth or during the neonatal period (i.e., during the first 28 days of life), where applicable. The newborn outcomes considered include fetus and newborn affected by maternal complications of pregnancy, fetus and newborn affected by complications of placenta, cord and membranes, birth weight, appearance, pulse, grimace, activity, and respiration (APGAR) score at 1 minute and 5 minutes, gestational age, neonatal infection, and neonatal mortality. These newborn outcomes will be assessed through mother-baby linkage.

Collaborators

Sophia Fleming - Chief Investigator - IQVIA Ltd ( UK )
Sumayya Mushtaq - Corresponding Applicant - IQVIA Ltd ( UK )
Christopher Lee - Collaborator - IQVIA Ltd ( UK )
Jess Ridsdale-Smith - Collaborator - IQVIA Ltd ( UK )
Niina-Maria Nissinen - Collaborator - IQVIA Finland Oy
Rownak Jahan Archie - Collaborator - IQVIA Solutions Sweden AB

Former Collaborators

Tarana Mehdikhanova - Collaborator - IQVIA Ltd ( UK )

Linkages

HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register