Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune modifying therapies: a nationwide cohort study in the OpenSAFELY platform

BackgroundIt is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes. MethodsWith the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate). FindingsWe identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding. InterpretationCOVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed on May 19th, 2021, using the terms "COVID-19", "SARS-CoV-2" and "rheumatoid arthritis", "psoriatic arthritis" "ankylosing spondylitis", "Crohns disease" "ulcerative colitis" "hidradenitis suppurativa" and "psoriasis", to identify primary research articles examining severe COVID-19 outcome risk in individuals with immune-mediated inflammatory diseases (IMIDs) and those on immune modifying therapy. The studies identified (including matched cohort studies and studies in disease-specific registries) were limited by small sample sizes and number of outcomes. Most studies did not show a signal of increased adverse COVID-19 outcomes in those on targeted therapies, with the exception of rituximab. Additionally, disease-specific registries are subject to selection bias and lack denominator populations. Added value of the studyIn our large population-based study of 17 million individuals, including 1 million people with IMIDs and just under 200,000 receiving immune modifying medications, we saw evidence that people with IMIDs had an increased risk of COVID-19-related death compared to the general population after adjusting for potential confounders (age, sex, deprivation, smoking status) (HR 1.23, 95%CI 1.20, 1.27). We saw differences by IMID type, with COVID-19-related death being increased by the most in people with inflammatory joint disease (HR 1.47, 95%CI 1.40, 1.54). We also saw some evidence that those with IMIDs were more likely, compared to the general population, to have COVID-19-related critical care admission/death (HR 1.24, 95%CI 1.21, 1.28) and hospitalisation (HR 1.32, 95%CI 1.29, 1.35). Compared to people with IMIDs taking standard systemics, we saw no evidence of differences in severe COVID-19-related outcomes with TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-6 inhibitors and JAK inhibitors. However, there was some evidence that rituximab was associated with an increased risk of COVID-19-related death (HR 1.68, 95%CI 1.11, 2.56) and death/critical care admission (HR 1.92, 95%CI 1.31, 2.81). We also saw evidence of an increase in COVID-19-related hospital admissions in people prescribed rituximab (HR 1.59, 95%CI 1.16, 2.18) or JAK inhibition (HR 1.81, 95%CI 1.09, 3.01) compared to those on standard systemics, although this could be related to worse underlying health rather than the drugs themselves, and numbers of events were small. This is the first study to our knowledge to use high-cost drug data on medicines supplied by hospitals at a national scale in England (to identify targeted therapies). The availability of these data fills an important gap in the medication record of those with more specialist conditions treated by hospitals creating an important opportunity to generate insights to these conditions and these medications Implications of all of the available evidenceOur study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for individuals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.

Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study

BackgroundIndirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression. ObjectiveCharacterise the factors associated with worsening psoriasis in the COVID-19 pandemic, using mental health status (anxiety and depression) as the main exposure of interest. MethodsGlobal cross-sectional study using a primary outcome of self-reported worsening of psoriasis. Individuals with psoriasis completed an online self-report questionnaire (PsoProtectMe; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection Me) between May 2020 and January 2021. Each individual completed a validated screen for anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-2). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results4,043 people with psoriasis (without COVID-19) from 86 countries self-reported to PsoProtectMe (mean age 47.2 years [SD 15.1]; mean BMI 27.6kg/m2 [SD 6.0], 2,684 [66.4%] female and 3,016 [74.6%] of white European ethnicity). 1,728 (42.7%) participants (1322 [77%] female) reported worsening of their psoriasis in the pandemic. A positive screen for anxiety or depression associated with worsening psoriasis in age and gender adjusted (OR 2.04, 95% CI 1.77-2.36), and fully adjusted (OR 2.01, 95% CI 1.72-2.34) logistic regression models. Female sex, obesity, shielding behaviour and systemic immunosuppressant non-adherence also associated with worsening psoriasis. The commonest reason for non-adherence was concern regarding complications related to COVID-19. ConclusionsThese data indicate an association between poor mental health and worsening psoriasis in the pandemic. Access to holistic care including psychological support may mitigate potentially long-lasting effects of the pandemic on health outcomes in psoriasis. The study also highlights an urgent need to address patient concerns about immunosuppressant-related risks, which may be contributing to non-adherence.

Risk mitigating behaviours in people with inflammatory joint and skin disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey

ObjectivesRegistry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse COVID-19 outcomes compared to patients receiving no systemic treatments. We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. MethodsOnline surveys were completed by individuals with Rheumatic and Musculoskeletal Diseases (RMD) (UK only) or psoriasis (globally) between 4th May and 7th September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterised international variation in a mixed effects model. ResultsOf 3,720 participants (2,869 psoriasis, 851 RMD) from 74 countries, 2,262 (60.8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term shielding). A greater proportion of those receiving targeted therapies (biologics and JAK inhibitors) reported shielding compared to those receiving no systemic therapy (adjusted odds ratio [OR] 1.63, 95% CI 1.35-1.97) and standard systemic agents (OR 1.39, 95% CI 1.22-1.56). Shielding was associated with established risk factors for severe COVID-19 (male sex [OR 1.14, 95% CI 1.05-1.24], obesity [OR 1.38, 95% CI 1.23-1.54], comorbidity burden [OR 1.43, 95% CI 1.15-1.78]), a primary indication of RMD (OR 1.37, 95% CI 1.27-1.48) and a positive anxiety or depression screen (OR 1.57, 95% CI 1.36-1.80). Modest differences in the proportion shielding were observed across nations. ConclusionsGreater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk mitigation strategies and may help inform updated public health guidelines as the pandemic continues. Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIAt the beginning of the COVID-19 pandemic, patients with immune mediated inflammatory diseases (IMIDs) on targeted systemic immunosuppressive therapy were considered to be at higher risk of severe COVID-19. Subsequent registry data suggest that this may not the case. C_LI What does this study add?O_LIHere we characterise shielding behaviour in patients with IMIDs from a global survey. We identified that targeted systemic therapy associates with increased shielding behaviour, as do demographic risk factors for severe COVID-19 including male gender and obesity. C_LIO_LIShielding behaviour varies across nations, albeit modestly when case-mix is taken into account. C_LI How might this impact on clinical practice or future developments?O_LIVariable shielding behaviour amongst patients with IMIDs may be an important confounder when considering differential COVID-19 risk between therapy types, so should be accounted for in analyses where possible. C_LI