Findings from a recent retrospective study conducted at Henry Ford Health System in Detroit, MI, showed patients treated with immunosuppressive therapies for inflammatory diseases (IMIDs) therapies were not at an increased risk for SARS-CoV-2 infection or severe COVID-19 outcomes.1
The retrospective chart review included 213 patients who were being treated with immunosuppressive therapies for IMIDs and were tested for SARS-CoV-2. Read our full coverage of the study.
In an interview with The Dermatologist, corresponding author Jesse Veenstra, MD, PhD, discussed these findings and their implications for clinical practice. Dr Veenstra is a board-certified dermatologist at Henry Ford Health System.
The Dermatologist: Why did you and your team conduct this study using patients at Henry Ford Health System?
Dr Veenstra: When COVID-19 first hit the United States, we did not know how patients taking immunosuppressive medications for IMIDs would be affected. Both clinicians and patients wanted to know if these medications could place someone at higher risk for contracting SARS-CoV-2, experiencing more severe disease, or even dying.
The initial thought was that since SARS-CoV-2 is a type of pathogen, and immunosuppressive therapies predispose individuals to infections, immunosuppressive therapies would put patients at higher risk of acquiring or having complications related to COVID-19. There were several research editorials and lectures that attempted to address these questions and provide some guidance for clinicians. However, this guidance was based on prior adverse effect reporting that did not include any information about coronavirus infections, let alone those caused by SARS-CoV-2, which has shown itself to be a completely different type of pathogen than those that commonly cause upper respiratory infections.
Many of these recommendations led providers to strongly consider discontinuing or holding immunosuppressive medications for their patients. We were specifically concerned about discontinuing medications for IMIDs, which could potentially lead to a disease flare and substantial immune dysregulation. Because Henry Ford Health System serves the greater metro Detroit region and was an original COVID-19 hot spot, we were in the unique position to begin collecting patient data focused on answering these questions.
The Dermatologist: Your findings showed several interesting points for practitioners, such as no association between COVID-19 outcomes and immunosuppressive therapy, possible increased risk of hospitalization with combination therapy, and possibly reduced risk with tumor necrosis factor (TNF) inhibitors. Could you elaborate more on these findings and how they help contribute to current understandings of the risk of SARS-CoV-2 infection and outcomes?
Dr Veenstra: In general, we found that IMID patients who receive immunosuppressive therapy are not at greater odds of COVID-19 infection or hospitalization related to COVID-19. Furthermore, no specific IMID led to increased odds of hospitalization. Our findings also mirror recent results from a global rheumatologic database study published by Gianfrancesco et al.2 This suggests that the mechanisms of COVID-19 infection and pathobiology are substantially different than other infections more common among those on immunosuppressive medications. Much of the new data regarding the pathobiology of COVID-19 and induction of inflammation also supports this idea, which is in turn reflected in some of the treatment regimens found to be effective in severe COVID-19, such as dexamethasone.
After controlling for other factors, we found that patients on multidrug therapy regimens did have greater odds of being hospitalized from COVID-19, while this association was not found with any monotherapy treatment. There are two likely explanations for this. First, combination drug therapy may have led to more profound immunosuppression, which influenced susceptibility to COVID-19 in some form. Second, patients requiring multidrug therapies may have had a greater burden of underlying disease and overall lower functional status, which either made them more susceptible to COVID-19 sequelae or greatly heightened the concern of the admitting provider, increasing odds of hospitalization independent of COVID-19 severity. This is something which will require further investigation.
We also found that patients on biologics had significantly lower odds of COVID-19-related hospitalization relative to the remainder of the cohort, which was primarily driven by TNF inhibitors. This was observed most prominently among patients on TNF inhibitor monotherapy but could also be seen among patients on multidrug regimens that included a TNF inhibitor. Although our study also investigated patients receiving other classes of biologics, such as IL-17 and IL-12/IL-23 inhibitors, we did not observe the same reduction in odds of hospitalization when these were used as a monotherapy, albeit there were a limited number of patients on these medications. Further study of IL-17 and IL-12/IL-23 inhibitors will be required to determine if they have the same impact as TNF inhibitors.
The Dermatologist: How do you think your study will impact clinical practice now and moving forward through the pandemic in the US? Do you think this and other studies will offer better guidance compared with previous editorials that only looked at clinical trial data on risk of infection with immunosuppressive therapies?
Dr Veenstra: Our study contributes to a new and growing repertoire of clinical data specific to SARS-CoV-2 and patient outcomes. It is imperative that clinicians have this information to better inform patient care during this period of uncertainty. While prior editorials and societal recommendations offered an important interim bridge to guide care, COVID-19-specific data such as ours is now available to provide guidance tailored to our current moment.
We hope the results of our study will provide dermatologists with greater confidence to either continue or resume immunosuppressive medications that they were previously questioning. These results also provide COVID-19-specific evidence that can be communicated with patients to help reassure them if their dermatologist asks them to continue taking their medication.
The Dermatologist: What are the limitations of your study? And, what additional research is needed to further support these findings so dermatologists can make the best treatment decisions possible during this time?
Dr Veenstra: This was a retrospective cohort study, and there are several limitations which are inherent to such an investigation. We attempted to avoid as many pitfalls as possible by using very specific inclusion and exclusion criteria with a thorough chart review of provider notes without relying on autopopulated data.
Our strategy of only reviewing patients within Henry Ford Health System who were tested for COVID-19 does create a selection bias and limits use of our data to infer absolute incidence of COVID-19 or provide commentary on those who were not tested, including asymptomatic individuals. Although our study included 213 patients with IMIDs, some medication classes (ie, IL-17 and IL-12/IL-23 inhibitors) were too infrequent to allow meaningful analysis and will require further investigation.
The Dermatologist: What key takeaways would you like to leave with our audience?
Dr Veenstra: The are several key takeaways, which include:
- Immunosuppressive therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae relative to the general population. Patients can be reassured if continuing or restarting these medications during the pandemic.
- TNF inhibitors may decrease odds of severe infection relative to other immunosuppressive therapeutics. However, there is no evidence to support switching from an already effective biologic to a TNF inhibitor. Further research is needed to investigate effects of other biologics (eg, IL-17 and IL-12/IL-23 inhibitors) on COVID-19 risk and sequelae.
- If a patient is on multidrug therapy with good disease control, consider transitioning to a single agent if feasible. If not possible, patients should be counseled about the greater odds of hospitalization.
In addition, COVID-19 continues to be a highly infectious pathogen that can lead to devastating consequences even among the healthiest individuals. Everyone, regardless of health status, should practice social distancing, wear a mask, and heed the advice of public health experts to prevent continued spread.
1. Veenstra J, Buechler CR, Robinson G, et al. Antecedent immunosuppressive therapy for immune-mediated inflammatory diseases in the setting of a COVID-19 outbreak. J Am Acad Dermatol. Published online July 28, 2020. doi:10.1016/j.jaad.2020.07.089
2. Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020;79(7):859-866. doi:10.1136/annrheumdis-2020-217871