Tumor Necrosis Factor Inhibitors and COVID-19 related hospitalization and death in patients suffering from immune-mediated inflammatory disease

Plain Language Summary

Tumor Necrosis Factor Inhibitors and COVID-19 related hospitalization and death in patients suffering from immune-mediated inflammatory disease

Study Title

Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Mortality Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.


Authors of original paper

Zara Izadi MPharm MAS, Erica J Brenner MD, Jinoos Yazdany MD MPH, Michael D Kappelman MD MPH, et al.

Lay summary contributors

Nadine Lalonde, Jean Liew, Mithu Maheswaranathan


  • Patients with immune-mediated inflammatory diseases (IMIDs) are potentially at higher risk of poor COVID-19 outcomes because of the disease process and the medications taken. 
  • IMIDs stem from defective immune responses that cause the patient’s body to develop inflammation in various tissues. 
  • The medications that some people with IMIDs take attempt to reduce inflammation and tissue damage by a variety of mechanisms, all altering the immune response in some way. These include biologic medications like Tumor Necrosis Factor Inhibitors (TNFi), which can be given as injections or as infusions through an IV.
  • TNFi and many other medications, as well as various IMID diseases, have been researched worldwide in relation to COVID-19. Studies have often been small, but this study is the first to pool results from three international COVID-19 registries to determine the effect of TNFi medications on COVID-19 outcomes.

Why is this important?

People with certain underlying conditions, including IMIDs, experience higher risk of poor outcomes in COVID-19. The way that TNFi medications work on the immune response could possibly have a protective effect in COVID-19. This study tries to identify if COVID-19 outcomes are better for patients taking TNFi alone compared to patients taking other medication regimens. Results can inform physicians regarding the risk related to various treatment regimens during the pandemic.


To compare COVID-19 outcomes in patients with preexisting IMIDs taking TNFi alone versus other IMID treatment regimens.

What was done?

The study determined outcomes of COVID-19 for a total of 6,077 adult patients (ages 18 years or older), from 74 countries, and from three international registries (GRA, SECURE-IBD, PsoProtect). 

Who was included? The sample included patients with inflammatory bowel disease (38.4%), psoriasis (4.9%), and various rheumatic diseases (56.6%). The most common disease diagnoses were Rheumatoid Arthritis, Crohn’s Disease, Ulcerative Colitis, and Ankylosing Spondylitis. The majority of patients were from Europe and North America. The mean age was 48.8 years and 58.6% were female. The most common comorbidities were high blood pressure, diabetes, obstructive lung disease, and cardiovascular disease. 

What medications were studied? The medication regimens studied were TNFi alone, which was designated as the reference for comparison, TNFi in combination with Methotrexate (MTX), TNFi in combination with Azathioprine (AZA) or Mercaptopurine (6MP), MTX alone, AZA alone, Janus kinase inhibitors (JAKi) alone. Patients using certain other medications (Sulfasalazine, Mesalamine, Hydroxychloroquine or Chloroquine, Leflunomide, oral Budesonide, and glucocorticoids) along with the aforementioned regimens were included in the study. 

What outcomes were considered? The outcomes considered were hospitalization only or death due to COVID-19.

What was found?

    • 21.3% of COVID-19 patients with IMIDs were hospitalized, and 3.1% died.
  • When compared to TNFi alone, higher odds of hospitalization and death were found with TNFi in combination with either AZA or 6MP, either AZA or 6MP alone, MTX alone, and JAKi alone, but not with TNFi in combination with MTX.
  • Both hospitalization and death were more common among patients included from the rheumatic diseases registry.
  • Other factors associated with higher odds of hospitalization or death included: older age, active IMID at COVID-19 diagnosis, obesity, lung disease, cardiovascular disease, diabetes, chronic kidney disease, use of Sulfasalazine, Leflunomide, or oral Budesonide, and higher daily Prednisone-equivalent glucocorticoid along with the studied treatment regimens.
  • Clustering of patients within country, calendar-month, and registry explained variation in the odds of hospitalization or death. This observation is likely because of factors affecting access to COVID-19 treatment and prevention such as availability in different countries, and when in the pandemic COVID-19 diagnosis occurred.

What does this mean?

  • These findings show that TNFi used alone or in combination with MTX is less likely to lead to poor outcomes in COVID-19. 
  • It is also encouraging that 75.6% of IMID patients with COVID-19 did not require hospitalization. 
  • Physicians can use study results such as these to help inform what precautions and treatments to consider in COVID-19 with IMID patients taking common treatment regimens. 

Some limitation of this study

  • Limitations of the study included the risk of reporting-bias (selective disclosure or withholding of information); however, the analysis suggested this was not a substantial concern. 
  • The threshold for hospitalization and how patients were treated for COVID-19 differed over the pandemic and these differences may have introduced bias. 
  • IMID history related to duration and previous therapies were not accounted for in this study.
  • The information in the registries were not completely uniform, but inconsistencies were addressed to the extent possible with registry specific analyses. 
  • Despite thorough analysis, other unforeseen factors may have affected the results.