Severe COVID-19–related death and hospital admissions were greater among individuals with immune-mediated inflammatory diseases (IMID) than in the general population, although most targeted immune-modifying therapies (TIMT) did not increase the risk for adverse COVID-19 outcomes in individuals with IMID. These were among study findings published recently in The Lancet Rheumatology.

Research suggests comorbidities may not be the only factors mediating the risk of severe COVID-19 outcomes among individuals with IMID receiving TIMT. Researchers sought to evaluate the risk for severe COVID-19 outcomes in adults with IMID. The study also assessed the outcomes of adults with IMID on TIMT (eg, biologics) vs those on standard systemic treatment (eg, methotrexate).

The investigators conducted a retrospective cohort study using data collected from OpenSAFELY (an electronic health records platform) and TPP (general practitioner software provider) that included more than 17 million adults from March 1 through September 30, 2020, to compare individuals with IMID vs general population with respect to the risk for COVID-19–related death, critical care admission or death, and hospital admission. Outcomes related to the use of standard systemic drugs vs TIMTs in people with IMID were also evaluated. TIMTs included tumor necrosis factor inhibitors; interleukin-12/23, -17, and -6 inhibitors; B-cell depletion therapy, and JAK inhibitors.

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The researchers identified 640,164 women and 523,274 men (71.1% White) with IMID, leaving over 16 million individuals with similar background in the general population cohort. In the IMID cohort 19,119 (1.6%) received TIMT vs 181,694 (15.6%) who received standard systemic therapy. After adjusting for age, sex, level of economic disadvantage (as measured by the English indices of deprivation), and smoking (HR 1.23; 95% CI, 1.20-1.27), and then adjusting for BMI, cardiovascular disease, diabetes, and glucocorticoid use (HR 1.15; 95% CI, 1.11-1.18) researchers found an increased risk for COVID-19–related death among individuals with IMID, as well as an increased risk for COVID-19–related critical care admission or death and hospital admission. Notably, all of these risks were greater among people who were identified by researchers as non-White.

Among individuals with IMID on TIMT, for the most part there was no increase in COVID-19-related death after adjusting for age, sex, economic disadvantage, BMI, IMID (bowel, joint, and skin), cardiovascular disease, cancer (except nonmelanoma skin cancer), stroke, and diabetes, then further adjusting for current glucocorticoid use. The exception to this was with rituximab, a B-cell depletion therapy, which was associated with increased COVID-19-related death (HR 1.68; 95% CI, 1.11-2.56) as well as increased risk for hospital admission and critical care.

Researchers concluded their findings suggested that “people with immune-mediated inflammatory diseases were at an increased risk of COVID-19–related death compared with people without immune-mediated inflammatory diseases of the same age, sex, deprivation, and smoking status. The mediator-adjusted effect estimates of our study also suggest that not all of the increased risk can be explained by mediation through comorbidities.” The investigators further noted that adults with IMID were more likely than the general population to be admitted to the hospital with COVID-19.

Study limitations include misclassification bias, residual confounding, imperfect assessment of glucocorticoid use, and differential exclusion.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


MacKenna B, Kennedy NA, Mehrkar A, et al. Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: A nationwide cohort study in the OpenSAFELY platform. Lancet Rheumatol. Published online June 9, 2022. doi:10.1016/S2665-9913(22)00098-4