Risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and those on immune-modifying therapies

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Jun 13 2022

In a recent study published in The Lancet Rheumatology, researchers assessed the risk of severe coronavirus disease 2019 (COVID-19) in adults with immune-mediated inflammatory diseases and those on immunomodulatory therapies.

Risks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity outcomes among individuals with inflammatory disorders and immunomodulatory therapies may not be entirely mediated by comorbid conditions and may vary with ethnicity.

About the study

In the present cohort study, researchers assessed the risks of severe SARS-CoV-2 infections among adults with inflammatory disorders and/or on immunomodulatory therapies.

Data were obtained from electronic health records of the OpenSAFELY platform, the public/publisher MEDLINE (PubMed) database, test productivity pack (TPP) software, and the United Kingdom (UK) Office for national statistics (ONS). English articles comprising systematic reviews and primary research data, in which the risks of COVID-19 severity outcomes were assessed among individuals with inflammatory disorders and individuals treated with immunomodulatory therapies were included for the analysis.

The data linked to hospitalization, mortality, and hospital prescriptions were analyzed. The study participants comprised >17 million subjects aged ≥18 years, registered in the TPP software with several general practitioners for ≥1 year prior to March 2020. Cox regression models were used to calculate hazard ratios (HRs) and compare the risks of SARS-CoV-2-associated mortality, critical care admissions or mortalities, and hospitalization (between 1 March and 30 September 2020).

The HRs were estimated for individuals with inflammatory disorders compared to the general public and individuals with inflammatory disorders on immunomodulatory therapeutic agents (e.g, biological agents) compared to individuals on the standard of care systemic therapy such as methotrexate.

The inflammatory disorders analyzed included inflammatory diseases of the joints (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis), inflammatory bowel disorders (ulcerative colitis, Crohn’s disease, or unclassified), and inflammatory dermatological disorders (hidradenitis suppurativa or psoriasis). The diagnosis was based on the international classification of diseases, tenth revision (ICD-10) codes.

Immunomodulatory drugs were categorized as standard therapy and targeted therapy. Standard therapeutic agents included were methotrexate, ciclosporin, leflunomide, mycophenolic acid or mycophenolate mofetil, sulphasalazine, thioguanine, azathioprine, and mercaptopurine. Targeted therapeutic agents included were tumor necrosis factor (TNF) inhibitors (adalimumab, etanercept, infliximab, golimumab, and certolizumab), interleukin (IL)-6,12,17,23 inhibitors, B lymphocyte depletion therapeutic agents (rituximab), and Janus kinase (JAK) inhibitors (tofacitinib and baricitinib).

The HRs were adjusted for several confounding variables (confounder-adjusted HR) and immune-mediators (mediator-adjusted HR). The confounding variables adjusted were sex, age, smoking habits, the presence of inflammatory disorders of the joints, skin, and bowel, stroke, and cancer except for non-melanoma cutaneous cancers and stroke. The mediators adjusted were diabetes, body mass index (BMI), cardiovascular disorders, and use of glucocorticoids. Further, ethnicity-stratified post-hoc analysis was performed.

Results

A total of 17,672,065 subjects, of which 1,163,438 subjects (55% females and 45% males, and 71% Whites) had inflammatory disorders, and 16,508,627 subjects (49.8% females and 50.2% males, and 64% of Whites) were included from the general public. Out of 1,163,438 subjects with immunological inflammatory disorders, 1.6% (n=19,119) were administered immunomodulatory therapeutic agents, whereas 15.6% (n=181,694) were administered standard systemic therapies.

Compared to the general public, individuals with inflammatory disorders showed a higher risk of SARS-CoV-2 infection-associated mortality after data adjustments for confounding variables (HR 1.2) and mediators (HR = 1.2). In addition, individuals with inflammatory disorders showed a higher risk of SARS-CoV-2 infection-associated admissions in critical care settings or mortality (confounder-adjusted HR and mediator-adjusted HRs were 1.2 and 1.2, respectively) and hospitalization (confounder-adjusted HR 1.3, and mediator-adjusted HR 1.2).

In the post-hoc analysis, the risks of SARS-CoV-2 infection severity outcomes among individuals with inflammatory disorders were greater among non-Whites than in Whites. No pieces of evidence of higher SARS-CoV-2-associated deaths among individuals treated with targeted therapy than individuals treated with standard systemic therapy (confounder-adjusted HR 1.0).

Likewise, no pieces of evidence were found for higher SARS-CoV-2 infection-associated death among individuals who were prescribed drugs such as TNF inhibitors, IL-6,12,17,23 inhibitors, and JAK inhibitors in comparison to individuals on standard systemic therapeutic agents. Individuals treated with rituximab showed higher SARS-CoV-2 infection-associated mortality (HR 1.7), with attenuation after individuals with hematological cancers and organ transplantations were excluded (HR 1.5).

Conclusion

Overall, the study findings showed that SARS-CoV-2 infection-associated deaths and hospitalizations were greater among individuals with inflammatory disorders. However, no increases in risks of SARS-CoV-2-associated severity outcomes were observed among individuals on the majority of the immunomodulatory therapeutic drugs for the treatment of inflammatory disorders in comparison to individuals treated with standard systemic therapeutic agents.