Summary Background The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and taking immune-modifying drugs may not be entirely mediated by comorbidities and may vary depending on factors such as ethnicity. Our objective was to evaluate the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those receiving immune-modifying therapies. Methods We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analyzing routinely collected primary care data related to hospital admission, death and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered in TPP practices with at least 12 months of primary care registrations before March 2020. We used Cox regression (adjusted for confounders and mediators ) to estimate hazard ratios (HR) comparing the risk of COVID-19-related death, intensive care admission, or death and hospital admission (March 1 to September 30, 2020) in people with immune-mediated inflammatory diseases in compared to the general population and in people with immune-mediated inflammatory diseases with targeted immune-modifying drugs (e.g., biologics) compared to those with standard systemic therapy (e.g., methotrexate). Results We identified 17,672,065 adults ; 1,163,438 adults (640,164 [55·0%] women and 523,274 [45·0%] men, and 827,457 [71·1%] white) had immune-mediated inflammatory diseases, and 16,508,627 people (8,215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] white ethnic group) were included as the general population. Of 1,163,438 adults with immune-mediated inflammatory diseases, 19,119 (1.6%) received targeted immunomodifying therapy and 181,694 (15.6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had a higher risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation and smoking; HR 1·23, 95% CI 1 ·20 –1·27) and further adjustment for mediators (body mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11–1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related intensive care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21–1·28; adjusted for mediators 1·16, 1·12–1·19) and hospitalization (adjusted for confounder 1·32, 1·29–1·35; adjusted for mediator 1·20, 1·17–1· 2. 3). In post-hoc analyses , the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-white ethnic groups than in white ethnic groups (as in the general population). We saw no evidence of an increase in COVID-19-related deaths in adults on targeted therapy, compared to those on standard systemic therapy, after adjusting for confounding factors (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [gut, joints and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke and diabetes (HR 1·03, 95% CI 0·80–1·33), and after further adjusting for use glucocorticoid current (1·01, 0·78–1·30). There was no evidence of an increase in COVID-19-related deaths in adults prescribed tumor necrosis factor inhibitors, interleukin (IL)-12/IL-23 inhibitors, IL-17 inhibitors, IL inhibitors -6, or Janus kinase inhibitors compared to those receiving standard systemic treatment. Rituximab was associated with an increase in COVID-19-related deaths (HR 1·68, 95% CI 1·11–2·56), with some attenuation after excluding people with hematological problems. malignant tumors or organ transplants (1·54, 0·95–2·49). Interpretation COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We did not see an increased risk of adverse COVID-19 outcomes in those receiving most immune-modifying drugs for immune-mediated inflammatory diseases compared to those receiving standard systemic therapy. |
Comments
A new analysis of 17 million GP records from patients in England provides important evidence for decisions about future booster vaccination programmes.
People with certain inflammatory immune conditions that affect the joints, intestines and skin, such as rheumatoid arthritis, may have had a higher risk of dying or needing hospital care if they contracted COVID-19 before vaccination compared to the population overall, according to a new study published in The Lancet Rheumatology .
The findings are based on analysis of 17 million GP records from patients in England during the first phase of the pandemic from March to September 2020, when the UK was in lockdown and before vaccines were available. Since then, many of the people treated with drugs analyzed in this study have been specifically targeted for the third dose of primary vaccine followed by boosters and are on a list of people offered antiviral treatments.
The study was carried out by a team from the London School of Hygiene & Tropical Medicine (LSHTM) using the OpenSAFELY platform with colleagues from St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, University of Oxford, King’s College London, the University of Exeter and the University of Edinburgh.
More than one million patients in the analysis had immune-mediated inflammatory diseases (IMID). These included inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, conditions affecting the joints such as rheumatoid arthritis, and skin conditions including psoriasis.
After taking into account age, sex, deprivation and smoking, research suggests that people with IMIDs affecting the gut, joints and skin had a 23% higher risk of COVID-19-related death and a 23% higher risk of COVID-related hospitalization compared to people without IMID before the introduction of vaccines and antiviral treatments.
People with inflammatory joint disease appeared to be at higher risk compared to those with intestinal or skin disease.
Compared to the general population, the researchers estimated the risk of death to be about eight additional deaths per 1,000 people with joint disease in one year (without taking into account other differences between people with and without joint disease, e.g. age and other health problems). conditions).
Study author Professor Sinéad Langan, Wellcome Senior Clinical Research Fellow and Professor of Clinical Epidemiology at LSHTM, said: “During the height of the pandemic in England in 2020, many people with inflammatory conditions affecting the gut were advised to joints and skin to stay home because doctors didn’t know how COVID-19 would affect them, or what the effects of medications like immune-modifying therapies used to treat IMIDs would be.
“Our study provides the most accurate assessment of the risk of severe COVID-19 before vaccination in people with IMID and with the medications used for their treatment. “We hope this analysis will help inform evidence-based policy as we continue to live with COVID-19.”
The team also investigated the impact of certain medications, identifying about 200,000 people taking immune-modifying medications. The study found that there was no increased overall risk of COVID-19 death or hospitalization for patients taking most immune-modifying drugs (often called biologics) compared to standard systemics (which work on the immune system). broader immune system) administered to treat this group of conditions.
For example, there was no increase in serious COVID-19 infections (death, admission to intensive care, or death or hospitalization) in people taking most of the targeted immune modifying therapies examined, including factor blockers. of tumor necrosis such as adalimumab, compared to the most commonly used standard. immunosuppressants such as methotrexate.
Professor Catherine Smith, consultant dermatologist at St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, said: "We know that certain factors, such as being older, increase a person’s risk of severe COVID-19 infection. 19. But until now we didn’t know whether the risk of severe COVID-19 increases with ongoing health conditions related to problems with the immune system, such as arthritis, Crohn’s disease and psoriasis.
“Our study provides important information that will help guide policymakers to ensure that prevention strategies, such as vaccination, and early intervention treatments, such as antivirals, are targeted to those most at risk.
“Overall, our findings regarding immune-modifying drugs are reassuring . “It is important that people continue taking prescribed medications and discuss treatment decisions with their doctors and get vaccinated according to recommendations.”
The OpenSAFELY platform accesses an unprecedented scale of data accessed through a trusted research environment to preserve an individual’s privacy. Provides the complete data set of all raw clinical events at single event level for all people in 40% of all GP practices in England, including all tests, treatments, diagnoses and clinical and demographic information linked to multiple hospital data sources, including for the first time, a complete data set of hospital-supplied medications.
This study was made possible by OpenSAFELY links to a new data source with information on "high-cost" medications. Because of the way these specialist medicines are prescribed, for example through schemes through home care companies, this means they are usually not on the GP’s records. The study marks the first time that researchers have been able to analyze this group of drugs in this way and highlights why access to this data is essential for research.
Co-author Dr Nick Kennedy, consultant gastroenterologist and senior clinical lecturer at the University of Exeter, said: “Our study is an example of the high-quality collaborative research that has been carried out during the pandemic using the innovative research platform from OpenSafely. For patients with inflammatory bowel disease, the overall message is reassuring, although there was some increased risk of being hospitalized in those who had COVID-19.
"Our research also shows that the targeted medications we commonly use to treat Crohn’s disease and colitis are not associated with an increased risk of poor outcomes."
The authors acknowledge limitations of the study, including the fact that people with these conditions may have protected or avoided COVID-19 infection and that other health problems, such as cardiovascular disease and diabetes, may affect COVID outcomes. -19 for people with IMID, as well as the possibility of misclassification of prescriptions or medications in patient records.
Implications of all available evidence Our study provides insights into future risk mitigation strategies and COVID-19 vaccination priorities for people with immune-mediated inflammatory diseases, as it highlights that patients with immune-mediated inflammatory diseases and those taking rituximab may be at risk for severe outcomes from COVID-19. Crucially, our study does not show a link between most targeted immune-modifying medications, compared to standard systemic therapy, and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes in people with immune-mediated inflammatory diseases and those treated with rituximab warrants further study. |
This study was supported by funding to investigators from the UK Medical Research Council and the Wellcome Trust.
